NZ210723A

NZ210723A - 2-heterocyclyl-6-hydroxy-lower alkyl-2-penem compounds and pharmaceutical compositions

Info

Publication number: NZ210723A
Application number: NZ210723A
Authority: NZ
Inventors: M Lang
Original assignee: Ciba Geigy Ag
Priority date: 1983-12-30
Filing date: 1984-12-21
Publication date: 1987-10-30
Also published as: EP0148128A3; DD228260A5; PT79762A; IL73966A0; HU194570B; KR850004764A; FI845141A0; DK613984D0; ES539205A0; AU3723684A; ES8706702A1; PH20547A; DK613984A; PT79762B; FI845141L; ES8801835A1; HUT36480A; GR82624B; EP0148128A2; NO845277L

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £10723 210723 NO DRAWINGS r*-' 2,<*C/SS/ Patents Form No. 5 NEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION "NOVEL OPTICALLY ACTIVE PENEM COMPOUNDS" WE, CIBA-GEIGY AG, a Swiss Corporation of Klybeckstrasse 141, 4002 Basle, Switzerland, hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement -1- ffoTIowed by page I A.) 2 107 23 - 14* 4-14723/1-3/+ Novel optically active penem compounds The invention relates to novel optically active penem compounds, to processes for their manufacture, to pharmaceutical preparations that contain such compounds, and to their use for the manufacture of pharmaceutical preparations or as pharmacologically active compounds. The invention relates especially to 2-hetero-cyclyl-6-hydroxy-lower alkyl-2-penem compounds of the formula in which Rj represents lower alkyl substituted by hydroxy or by protected hydroxy, R2 represents an unsaturated azaheterocyclyl radical bonded via a ring nitrogen atom to the penem radical, and R3 represents - 2 - 2 1 f) ^ carboxy or functionally modified carboxy, to optical isomers of compounds of the formula I, to mixtures of these optical isomers, and to salts of such compounds of the formula I having a salt-forming group. Within the scope of the present description, the definitions used hereinbefore and hereinafter preferably have the following meanings: An unsaturated azaheterocyclyl radical R2 bonded via a ring nitrogen atom to the penem radical is especially a corresponding monocyclic or polycyclic, especially monocyclic or bicyclic, or also tricyclic, azaheterocyclyl radical, such as an optionally partially saturated monocyclic 5-membered heteroaryl radical having from 1 to 4 ring nitrogen atoms, for example a corresponding aza-, diaza-, triaza- or tetraza-cyclic radical of aromatic character or a corresponding dihydro radical, or a corresponding partially saturated monocyclic 6-membered heteroaryl radical having from 1 to 3 ring nitrogen atoms, such as a corresponding aza-, diaza- or triaza-cyclic radical, for example a corresponding dihydro or tetrahydro radical, and also optionally partially saturated benzo, dibenzo, pyrido or pyrimido derivatives of such 5- or 6-membered radicals. Corresponding azaheterocyclyl radicals R2 are, for example, optionally partially saturated pyrrolyl, diazolyl, triazolyl or tetrazolyl; and also partially saturated pyridyl, pyrimidyl, pyridazinyl, pyrazinyl or triazinyl; and benzopyrrolyl, benzodiazolyl, benzotriazolyl, pyridopyrrolyl, pyrido-diazolyl, pyridotriazolyl, pyrimidopyrrolyl, pyrimido-diazolyl, pyrimidotriazolyl or dibenzopyrrolyl optionally partially saturated in the pyrrolyl, diazolyl or triazolyl moiety and/or in the benzo, pyrido or pyrimido moiety; and also benzopyridyl, benzopyrimidyl, benzopyridazinyl, benzopyrazinyl, / 2 107?3 ~ benzotriazinyl, pyridopyridyl, pyridopyrimidyl, pyridopyridazinyl, pyridopyrazinyl, pyridotriazinyl, pyrimidopyridyl, pyrimidopyrimidyl, pyrimido-pyridazinyl, pyrimidopyrazinyl, pyriraidotriazinyl, dibenzopyridyl or dibenzopyrazinyl partially saturated in the pyridyl, pyrimidyl, pyridazinyl, pyrazinyl or triazinyl moiety and optionally partially saturated in the benzo, pyrido or pyrimido moiety. Radicals R2 are unsubstituted or may be substituted, such as, especially, mono- or poly-substituted, more especially mono- or di-substituted, by optionally etherified or esterified hydroxy, for example hydroxy, lower alkoxy, lower alkanoyloxy or halogen, optionally etherified mercapto, for example mercapto, lower alkyl-thio or phenylthio, lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, halo-lower alkyl, lower alkylthio-lower alkyl, optionally N-lower alkylated amino-lower alkyl, for example amino-lower alkyl, lower alkylamino-lower alkyl or di-lower alkylamino-lower alkyl, lower alkanoylamino-lower alkyl, aminocarboxy-lower alkyl, amino-lower alkoxy-carbonyl-lower alkyl, sulpho-lower alkyl, optionally substituted amino, for example amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino or acylamino, such as lower alkanoylamino, optionally functionally modified carboxy or sulpho, for example carboxy, esterified carboxy, such as lower alkoxycarbonyl, optionally substituted carbamoyl, such as carbamoyl or N-mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho or sulphamoyl, or phenyl optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, or cyclo-alkyl, nitro, imino, oxo and/or by oxido. Radicals R2 are especially substituted at the ring carbon - 4 - 2 107 atoms, but may also be substituted at the ring nitrogen atoms. Functionally modified carboxy Rj is especially esterified carboxy that can be cleaved under physiological conditions or protected carboxy R3'. An esterified carboxy group R-j that can be cleaved under physiological conditions protects the compounds of the formula I from forming a salt in the gastrointestinal tract in the case of oral administration, premature excretion being prevented as a result, and is especially an acyloxymethoxycarbonyl group in which acyl represents, for example, the radical of an organic carboxylic acid, especially an optionally substituted lower alkanecarboxylic acid, or in which acyloxymethyl forms the radical of a lactone. Such groups are, for example, lower alkanoyloxymethoxy-carbonyl, amino-lower alkanoyloxymethoxycarbonyl, especially a-amino-lower alkanoyloxymethoxycarbonyl, 4-crotonolactonyl and 4-butyrolacton-4-yl. Further esterified carboxy groups R^ that can be cleaved under physiological conditions are, for example, 5-indanyloxycarbonyl, phthalidyloxycarbonyl, 1-lower alkoxycarbonyloxy-lower alkoxycarbonyl, 1-lower alkoxy-lower alkoxycarbonyl or 2-oxo-1,3-dioxolen-4-ylmethoxy-carbonyl which is optionally substituted in the 5-position of the dioxolene ring by lower alkyl or phenyl. In the present description, the term "lower" used in connection with definitions of groups and compounds denotes that, unless expressly defined otherwise, the groups and compounds so designated contain from 1 to 7, preferably from 1 to 4, carbon atoms. Hydroxy-substituted lower alkyl Rj is especially lower alkyl substituted by hydroxy in the a-position relative to the penem ring structure and represents, for example, 1-hydroxyprop-1-yl, 2-hydroxyprop-2-yl, 1-hydroxybut-1-yl or 2-hydroxybut-2-yl or, especially, hyd roxymethyl or 1-hydroxyethyl. Lower alkoxy is, for example, methoxy, also ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert.-butoxy, or n-pentyloxy, n-hexyloxy or n-heptyloxy. Lower alkanoyloxy is, for example, acetoxy or propionyloxy. Halogen is, for example, fluorine, chlorine, bromine or iodine. Lower alkylthio is, for example, methylthio, ethylthio, n-propylthio, isopropylthio or n-butylthio. Lower alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec.-butyl or tert.-butyl, also n-pentyl, n-hexyl or n-heptyl. Hydroxy-lower alkyl as substituent of an azaheterocyclyl radical R2 is, for example, hydroxy-methyl, 2-hydroxyethyl or 2,3-dihydroxypropyl. Lower alkanoyloxy-lower alkyl is, for example, acetoxymethyl or 2-acetoxyethyl. Lower alkoxy-lower alkyl is, for example, methoxy-methyl, 2-methoxyethyl, ethoxymethyl or 2-ethoxysthyl. Carboxy-lower alkyl is, for example, carboxy-methyl, 1-carboxy-, 2-carboxy- or 1,2-dicarboxy-ethyl. Lower alkoxycarbonyl-lower alkyl is, for example, methoxycarbonylmethyl, ethoxycarbonylmethyl or 2-methoxycarbonylethyl. Carbamoyl-lower alkyl is, for example, carbamoyl-methyl or 2-carbamoylethyl, whilst carbamoyloxy-lower alkyl is, for example, carbamoyloxymethyl or 2-carba-moyloxyethyl. Halo-lower alkyl is, for example, chloromethyl, bromomethyl, 2-chloroethyl or 2,2-dichloroethyl. Lower alkylthio-lower alkyl is, for example, - 6 - 2 10723 " methylthiomethyl, ethylthiomethyl, n-propylthiomethyl or 2-methylthioethyl. Amino-lower alkyl is, for example, aminomethyl or 2-aminoethyl, whilst lower alkylamino-lower alkyl is, for example, methylaminomethyl, ethylaminomethyl, 2-methylaminoethyl or 2-ethylaminoethyl, and di-lower alkylamino-lower alkyl is, for example, dimethylaminomethyl , 2-dimethylaminoethyl or 2-diethylaminoethyl. Lower alkanoylamino-lower alkyl is, for example, acetaminomethyl, 2-acetaminoethyl or formylaminomethyl. Aminocarboxy-lower alkyl is, for example, 2-amino-2-carboxyethyl or 1-amino-1-carboxymethyl, whilst amino-lower alkoxycarbonyl-lower alkyl is, for example, 2-amino-2-methoxy- (or 2-ethoxy-)carbonylethyl. Sulpho-lower alkyl is, for example, sulphomethyl or 2-sulphoethyl. Lower alkylamino is, for example, methylamino, ethylamino, n-propylamino, isopropylamino or n-butyl-amino, whilst di-lower alkylamino is, for example, dimethylamino, diethylamino, di-n-propylamino or di-isopropylamino. Lower alkyleneamino has especially from 4 to 6 carbon chain members and represents, for example, pyrrolidino or piperidino. Lower alkanoylamino is, for example, acetylamino or propionylamino. Lower alkoxycarbonyl is, for oxample, methoxy-carbonyl or ethoxycarbonyl. N-mono-lower alkylated carbamoyl is, for example, N-methyl-, N-ethyl- or N-propyl-carbamoyl, whilst N,N-di-lower alkylated carbamoyl is, for example, N,N-dimethyl- or N,N-diethyl-carbamoyl. Cycloalkyl preferably contains from 3 to 8, especially 5 or 6, ring members and is, for example, cyclppentyl or cyclohexyl, also cyclopropyl or cyclo- 2 10723 heptyl. Lower alkanoyloxymethoxycarbonyl is, for example, acetoxymethoxycarbonyl or pivaloyloxymethoxycarbonyl. cx-amino-lower alkanoyloxymethoxycarbonyl is, for example, glycyloxymethoxycarbonyl, valyloxymethoxy-carbonyl or leucyloxymethoxycarbonyl. 1-lower alkoxycarbonyloxy-lower alkoxycarbonyl is, for example, ethoxycarbonyloxymethoxycarbonyl or 1-ethoxycarbonyloxyethoxycarbonyl. 1-lower alkoxy-lower alkoxycarbonyl is, for example, methoxymethoxycarbonyl or 1-methoxyethoxy-carbonyl. A 2-oxo-1,3-dioxolen-4-ylmethoxy group which is optionally substituted in the 5-position of the dioxo-lene ring by lower alkyl or phenyl is especially a 5-phenyl- and, more especially, a 5-methyl-2-oxo-1,3-dioxolen-4-ylmethoxy group. Corresponding 5-membered optionally partially saturated monocyclic heteroaryl radicals R2 are, for example, pyrrolyl or dihydropyrrolyl optionally substituted, for example, by lower alkyl or by halogen, for example 1-pyrrolyl, 3-methyl-1-pyrrolyl, 3,4-dichloro-1-pyrrolyl, and also 2,3- or 2,5-dihydro-1-pyrrolyl, diazolyl, such as imidazolyl or pyrazolyl, optionally substituted, for example, by lower alkyl, lower alkoxy, amino-lower alkyl, N-lower alkylated amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carba-moyl-lower alkyl, carbamoyloxy-lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, halo-lower alkyl, sulpho-lower alkyl, lower alkylthio-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkanoylamino or by nitro, for example 1-imidazolyl, 1-pyrazolyl, 4-lower alkyl-1-pyrazolyl, 2-amino-, 4-lower - 8 - 2 107 alkoxy-, 4-lower alkyl-, 4,5-di-lower alkyl-, 2-amino-lower alkyl, 4-amino-lower alkyl-, 4-lower alkanoylamino-lower alkyl-, 2-hydroxy-lower alkyl-, 4-hydroxy-lower alkyl-, 4-lower alkanoyloxy-lower alkyl-, 2- or 4-amino-carboxy-lower alkyl-, 4-carbamoy1-lower alkyl-, 4-carbamoyloxy-lower alkyl-, 4-halo-lower alkyl-, 4-lower alkylthio-lower alkyl- or 2-nitro-1-imidazolyl, 2-lower alkylpyrazolio or 3-lower alkylimidazolio, triazolyl, such as 1H-1,2,3-triazol-1-yl, 1H—1,2,3— triazol-2-yl, 1H-1,2,4-triazol-1-yl or 1H —1,3,4 — triazol-1-yl, optionally substituted, for example, by lower alkyl, carboxy-lower alkyl, amino or by phenyl, for example the corresponding unsubstituted radicals and 4- or 5-methyl-1,2,3-triazol-1-yl, 3-methyl- or 3-phenyl-1H-1,2,4-triazol-1-yl or 1-(2-methyl- or 4-methyl-lH-1,2,4-triazolio), or tetrazolyl, such as 1H-tetrazol-1-yl or 2H-tetrazol-2-yl, optionally substituted, for example, by lower alkyl, carboxy-lower alkyl, sulpho-lower alkyl, di-lower alkylamino-lower alkyl, amino or by optionally halo-substituted phenyl, for example the corresponding unsubstituted radicals and 5-amino-, 5-methyl-, 5-carboxymethyl-, 5-sulpho-methyl-, 5-(2-dimethylaminoethyl) - or 5-phenyl-1H-tetrazol-1-yl, or 5-amino-, 5-methyl-, 5-carboxy-methyl-, 5-sulphomethyl-, 5-(2-dimethylaminoethyl)-or 5-phenyl-2H-tetrazol-2-yl. Corresponding 6-membered partially saturated monocyclic heteroaryl radicals R2 are, for example, dihydro-1-pyridyl, such as 2H-1,2-dihydro- or 4H-1,4-dihydro-1-pyridyl, that is unsubstituted or, especially, substituted, for example by oxo, and optionally additionally substituted, for example by halogen, for example 2-oxo-2H-1,2-dihydro-1-pyridyl or 4-oxo-4H-1 , 4-dihydro-1-pyridyl, or dihydro- or tetrahydro-1-pyrimidyl, such as 2H-1 , 2-dihydro-, 4H-1 , 4-dihydro- or / "10723 „> <c" - 9 - > , 1,2,3,4-tatrahydro-1-pyrimidyl, that is optionally substituted, especially substituted, for example by oxo, and optionally additionally substituted, for example by lower alkyl, amino, di-lower alkylamino and/or by carboxy, for example 2-oxo-1,2-dihydro-1-pyrimidyl, 6-methyl-, 5-methyl-, 5-carboxy- or 6-carboxy-2-oxo-1,2-dihydro-1-pyrimidyl, 4-amino-2-oxo- 1,2-dihydro-1-pyrimidyl (cytosyl), 4-oxo-1,4-dihydro-1- ^- pyrimidyl, 2, 4-dioxo-1 , 2, 3, 4-tetrahyd ro-1-pyrimidyl or ! . i t 5-methyl-2,4-dioxo-1 ,2,3,4-tetrahydro-1 -pyrimidyl, or dihydro- or tetrahydro-triazinyl, such as 2H-1,2- dihydro-1 , 3, 5-triazin-1-yl, 2H-1 , 2-dihydro-1 , 2, 4- triazin-1-yl, 1,2,5,6-tetrahydro-1,2,4-triazin-1-yl or 1,2,3,4-tetrahydro-1,3,6-triazin-1-yl, optionally ; - substituted, for example, by lower alkyl, lower alkoxy, amino and/or by up to 2 oxo groups, for example 4-amino- ! 2-oxo-l,2-dihydro-1,3,5-triazin-1-yl (5-azacytosyl), 4- | • lower alkyl-1,4, 5,6-tetrahydro-5,6-dioxo-1,2,4-triazin- I 1-yl, for example 4-methyl-1,4,5,6-tetrahydro-5,6-dioxo- 1,2,4-triazin-1-yl, 2,4-dioxo-1,2,3,4-tetrahydro-1,3,6- triazin-1-yl (6-azauracyl) or 2,4-dioxo-5-methyl- 1,2,3,4-tetrahydro-1,3,6-triazin-1-yl (4-azathymyl). Optionally substituted and optionally partially / saturated benzo, dibenzo, pyrido and pyrimido derivatives of the mentioned monocyclic azaheterocyclyl radicals R2 are especially those of the pyrrol-1-yl, imidazol-1-yl and triazol-1-yl radicals, more especially indol-1-yl, carbazol-9-yl, benzoimidazol-1-yl, benzotriazol-1-yl, pyridopyrrol-1-yl, for example j lH-pyrrolo(2, 3—b) pyrid-1 -yl, pyridoimidazol-1-yl, for example IH-imidazo(4,5-b)pyrid-1-yl, or pyrimido-, d ihydropyrimido- or tatrahydropyr imido- imidazol-1 -yl optionally substituted, for example, by amino, imino and/or by oxo, for example purin-l-yl, hypoxanthyl, adenyl or guanyl, or pyrimido-, dihydropyrimido- or I ***** / 2 10723 ** -10- tetrahydropyrimido-1 , 2,3-triazol-1-yl optionally substituted, for example, by amino, imino and/or by oxo, for example 8-azahypoxanthyl, 8-azaadenyl or 8-azaguanyl. Preferred radicals R2 are pyrrol-1-yl, pyrazol-1-yl, 1, 2, 4-triazol-1-yl, tetrazol-1-yl, benzo imidazol-1 -yl, indol-1-yl, benzotriazol-1-yl, 1H-pyrrolo(2,3-b)-pyrid-1-yl, IH-imidazo(4,5-b)pyrid-1-yl and purin-1- yl, each of which is unsubstituted or substituted, for t . example, as indicated, and especially imidazol-1-yl that is unsubstituted or substituted, for example, as indicated. Preferred esterified carboxy groups R3 that can be cleaved under physiological conditions are, for ; example, phthalidyloxycarbonyl, lower alkanoyloxy-methoxycarbonyl, for example acetoxymethoxycarbonyl or i pivaloyloxymethoxycarbonyl, and 1-lower alkoxy- ! - carbonyloxy-lower alkoxycarbonyl, for example 1-ethoxy- j carbonyloxyathoxycarbonyl. The functional groups present in compounds of the formula I, such as hydroxy, carboxy, amino or sulpho groups, especially the hydroxy group in the radical R| and the carboxy group R3, are optionally protected by protecting groups used in penem, penicillin, cephalosporin and peptide chemistry. Such protecting groups protect the functional groups in question from undesired condensation reactions, substitution reactions and the like during the synthesis of the compound of the formula I from its precursors. Such protecting groups can be removed readily, that is to say without undesirable secondary reactions taking place, for example by means of solvolysis or reduction, or alternatively under physiological conditions. Protecting groups of this type and the methods by - 11 - 2 107 which they are introduced and removed are described, for example, in J.F.W. McOmie, "Protective Groups in Organic Chemistry", Plenum Press, London, New York, 1973, T.W. Greene, "Protective Groups in Organic Synthesis", Wiley, New York, 1981, "The Peptides", Vol. I, Schroeder and Luebke, Academic Press, London, New York, 1965 and Houben-Weyl, "Methoden der Organischen Chemie", Volume 15/1, Georg Thieme Verlag, Stuttgart, 1974. In compounds of the formula (I), a hydroxy group in the radical Rj, and also a hydroxy group in the radical R2, may be protected, for example, by acyl radicals. Suitable acyl radicals are, for example, lower alkanoyl optionally substituted by halogen, for example acetyl or trifluoroacetyl, benzoyl optionally substituted by nitro, for example benzoyl, 4-nitro-benzoyl or 2, 4-dinitrobenzoyl, lower al koxycarbonyl optionally substituted by halogen, for example 2-bromoethoxycarbonyl or 2,2,2-trichloroethoxycarbonyl, lower alkenyloxycarbonyl, for example allyloxycarbonyl, or phenyl-lower alkoxycarbonyl optionally substituted by nitro, for example 4-nitrobenzyloxycarbonyl. Further suitable hydroxy-protecting groups are, for example, tri-substituted silyl, such as tri-lower alkylsilyl, for example tr imethyl silyl or tert.-butyldimethylsilyl, 2-halo-lower alkyl groups, for example 2-chloro-, 2-bromo-, 2-iodo- and 2,2,2-trichloro-ethyl, and phenyl-lower alkyl optionally substituted by halogen, for example chlorine, lower alkoxy, for example methoxy, and/or by nitro, such as corresponding benzyl. Tri-lower alkylsilyl and lower alkenyloxygarbonyl are preferred as hydroxy-protecting g roups. A carboxy group R3, and also a carboxy group in -12- ? * n \ j the radical R2, is customarily protected in esterified form, the ester group being readily cleavable under mild conditions, for example under mildly reductive, such as hydrogenolytic, conditions or under mildly solvolytic, such as acidolytic or especially basically or neutrally hydrolytic, conditions. A protected carboxy group can also be an esterified carboxy group that can readily be converted into a different functionally modified carboxy group, such as into a different esterified carboxy group. Such esterified carboxy groups contain as estarifying groups especially lower alkyl groups that are branched in the 1-position or suitably substituted in the 1- or 2-position. Preferred carboxy groups in esterified form are, inter alia, lower alkoxycarbonyl, for example methoxycarbonyl, ethoxycarbonyl, iso-propoxycarbonyl or tert.-butoxycarbonyl, and (hetero)arylmethoxycarbonyl having from 1 to 3 aryl radicals or having a monocyclic heteroaryl radical, these optionally being mono- or poly-substituted, for example by lower alkyl, such as tert.-lower alkyl, for example tert.-butyl, halogen, for example chlorine, and/or by nitro. Examples of such groups are benzyloxycarbonyl optionally substituted, for example, as mentioned above, for example 4-nitrobenzyloxy-carbonyl, diphenylmethoxycarbonyl or triphenylmethoxy-carbonyl optionally substituted, for example, as mentioned above, for example diphenylmethoxycarbonyl, or picolyloxycarbonyl, for example 4-picolyloxycarbonyl , or furfuryloxycarbonyl, such as 2-furfuryl-oxycarbonyl, each optionally substituted, for example, as mentioned above. Further suitable groups are lower alkanoylmethoxycarbonyl, such as acetonyloxycarbonyl, aroylmethoxycarbonyl, in which the aroyl group preferably represents benzoyl optionally substituted, 2 10 for example, by halogen, such as bromine, for example phenacyloxycarbonyl, halo-lower alkoxycarbonyl, such as 2-halo-lower al koxycarbonyl, for example 2,2,2-trichloroethoxycarbonyl, 2-chloroethoxycarbonyl, 2-bromoethoxycarbonyl or 2-iodoethoxycarbonyl, or -halo-lower alkoxycarbonyl in which lower alkoxy contains from 4 to 7 carbon atoms, for example 4-chlorobutoxy-carbonyl, phthal imidomethoxycarbonyl, lower alkenyloxycarbonyl, for example allyloxycarbonyl, or ethoxy-carbonyl substituted in the 2-position by lower alkyl-sulphonyl, cyano or by tri-substituted silyl, such as tri-lower alkylsilyl or triphenylsilyl, for example 2-methylsulphonylethoxycarbonyl, 2-cyanoethoxycarbonyl, 2-trimethylsilylethoxycarbonyl or 2-(di-n-butylmethyl-silyl) -ethoxycarbonyl. Other protected carboxy groups in esterified form are corresponding organic silyloxycarbonyl groups, and also corresponding organic stannyloxycarbonyl groups. In these groups the silicon or tin atom preferably has lower alkyl, especially methyl or ethyl, and also lower alkoxy, for example methoxy, as substi-tuents. Suitable silyl and stannyl groups are especially tri-lower alkylsilyl, especially trimethyl-silyl or dimethyl-tert.-butyl silyl, or correspondingly substituted stannyl groups, for example tri-n-butyl-stannyl. Preferred projected carboxy groups ' are the 4-nitrobenzyloxycarbonyl and lower alkenyloxycarbonyl, especially allyloxycarbonyl, groups and the ethoxycarbonyl group substituted in the 2-position by lower al kylsulphonyl, cyano or by tri-lower alkylsilyl, for example tr imethyl silyl or d i-n-butylmethyl silyl . A. protected amino group in the radical R2 can be, for example, in the form of a readily cleavable acylamino, acylimino, etherified mercaptoamino, silyl- -14- *> 4 O amino or stannylamino group or in the form of an enamino, nitro or azido group. In a corresponding acylamino group, acyl is, for example, the acyl radical of an organic acid having, for example, up to 18 carbon atoms, especially an alkanecarboxylic acid optionally substituted, for example, by halogen or phenyl, or of a benzoic acid optionally substituted, for example, by halogen, lower alkoxy or nitro, or of a carbonic acid semiester. Such acyl groups are, for example, lower alkanoyl, such as formyl, acetyl or propionyl, halo-lower alkanoyl, such as 2-haloacetyl, especially 2-fluoro-, 2-bromo-, 2-iodo-, 2,2,2-trifluoro- or 2,2,2-trichloro-acetyl, optionally substituted benzoyl, for example benzoyl, halobenzoyl, such as 4-chlorobenzoyl, lower alkoxy-benzoyl, such as 4-methoxybenzoyl, or nitrobenzoyl, such as 4-nitrobenzoyl. Especially suitable are also lower alkenyloxycarbonyl, for example allyl oxycarbonyl, or lower alkoxycarbonyl optionally substituted in the 1- or 2-position, such as lower alkoxycarbonyl, for example methoxy- or ethoxy-carbonyl, optionally substituted benzyloxycarbonyl, for example benzyloxy-carbonyl or 4-nitrobenzyloxycarbonyl, aroylmethoxy-carbonyl in which the aroyl group preferably represents benzoyl optionally substituted, for example, by halogen, such as bromine, for example phenacyloxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2,2,2-trichloroethoxycarbonyl, 2-chloroethoxycarbonyl, 2-bromoethoxycarbonyl or 2-iodoethoxycarbonyl, or 2-(tri-substituted silyl)-ethoxycarbonyl, such as 2-tri-lower alkylsilylethoxycarbonyl, for example 2- trimethylsilylethoxycarbonyl or 2-(di-n-butylmethyl-silyl)-ethoxycarbonyl, or 2-triarylsilylethoxycarbonyl, such as 2-triphenylsilylethoxycarbonyl. In an acylimino group, acyl is, for example, the - 15 - 2 acyl radical of an organic dicarboxylic acid having, for example, up to 12 carbon atoms, especially of a corresponding aromatic dicarboxylic acid, such as phthal ic acid. Such a group is especially phthal im ino. An etherified mercaptoamino group is especially a phenylthioamino group optionally substituted by lower alkyl, such as methyl or tert.-butyl, lower alkoxy, such as methoxy, halogen, such as chlorine or bromine, and/or by nitro, or a pyridyl thioamino group. Corresponding groups are, for example, 2- or 4-nitrophenyl-thioamino or 2-pyr idyl thioamino . A silyl- or stannyl-amino group is especially an organic silyl- or stannyl-amino group in which the silicon or tin atom preferably contains as substi-tuent(s) lower alkyl, for example methyl, sthyl, n-butyl or tert.-butyl, also lower alkoxy, for example methoxy. Corresponding silyl or stannyl groups are especially tri-lower alkylsilyl, especially trimethyl-silyl, also dimethyl-tert .-butylsilyl, or correspondingly substituted stannyl, for example tri-n-butyl-stannyl . Further protected amino groups are, for example, enamino groups that contain an electron-attracting substituent, for example a carbonyl group, at the double bond in the 2-position. Protecting groups of this type are, for example, 1-acyl-lower alk-1-en-2-yl radicals in which acyl represents, for example, the corresponding radical of a lower al kanecarboxyl ic acid, for example acetic acid, of a benzoic acid optionally substituted, for example, by lower alkyl, such as methyl or tert.-butyl, lower alkoxy, such as methoxy, halogen, such as chlorine, and/or by nitro, or especially of a carbonic acid semiester, such as a carbonic acid lower alkyl semiester, for example a - 16 - 2 1 07 carbonic acid methyl semiester or ethyl semiester, and in which lower alk-l-ene represents especially 1-propene. Corresponding protecting groups are especially 1-lower al kanoylprop-1 -en-2-yl, for example 1 -acetyl prop-1 -en-2 -yl, or 1-lower al koxycarbonyl prop-1 -en-2-yl, for example 1-ethoxycarbonylprop-1-en-2-yl . Preferred protected amino groups are, for example, azido, phthalimido, nitro, lower al kenyl oxycarbonyl -amino, for example allyloxycarbonylamino, and optionally nitro-substituted benzyloxycarbonylamino. A protected sulpho group in the radical R2 is especially an esterified sulpho group, such as a sulpho group esterified by an aliphatic, cycloal iphatic, cycloaliphatic-aliphatic, aromatic or araliphatic alcohol, for example a lower alkanol, or by a silyl or stannyl radical, such as tri-lower alkylsilyl. In a sulpho group the hydroxy group may be etherified, for example, in the same manner as the hydroxy group in an esterified carboxy group. Salts of compounds according to the invention are especially pharmaceutical^ acceptable, non-toxic salts of compounds of the formula I. Such salts are formed, for example, from the acidic groups, for example the carboxy and sulpho groups, present in compounds of the formula I and are especially metal or ammoniun salts, such as alkali metal and alkaline earth metal salts, for example sodium, potassiun, magnesium or calcium salts, and ammonium salts with ammonia or suitable organic amines, such as lower alkylamines, for example triethylamine, hydroxy-lower alkylamines, for example 2-hyd roxyethyl amine, bis- (2-hyd roxyethyl)-amine or tris-(2 -hyd roxyethyl)-amine , basic aliphatic esters of carboxylic acids, for example 4-aminobenzoic acid 2-diethylaminoethyl ester, lower alkyleneamines, for example 1-ethylpiperidine, cycloalkylamines, for - 17 - 7 10723 example dicyclohexyl amine, or benzyl amines, for example N,N'-dibenzylethylenediamine, dibenzylamine or N-benzyl-3-phenethylamine. Compounds of the formula I having a basic group, for example having an amino group, can form acid addition salts, for example with inorganic acids, such as hydrochloric acid, sulphuric acid or phosphoric acid, or with suitable organic carboxyl ic or sulphonic acids, for example acetic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, oxalic acid, citric acid, benzoic acid, mandelic acid, malic acid, ascorbic acid, methanesulphonic acid or 4-toluene-sulphonic acid. Compounds of the formula I having an acidic group and a basic group can also be in the form of internal salts, that is to say in zwitterionic form. For the purposes of isolation or purification it is also possible to use pharmaceutially unacceptable salts. Only the pharmaceutically acceptable, non-toxic salts are used therapeutically and these are therefore preferred. The penem compounds of the formula I may have an additional chirality centre in the substituent R|. For example, 1-hydroxyethyl as the substituent Rj may be present in the R-, S- or racemic R,S-configuration. In preferred penem compounds of the formula I, a radical Rj having an asymmetric carbon atom, especially 1-hydroxyethyl, has the R-configuration. The invention relates especially to compounds of the formula I in which Rj represents lower alkyl substituted by hydroxy or by protected hydroxy, R2 represents an optionally partially saturated monocyclic 5-membered heteroaryl radical that has from 1 to 4 ring nitrogen atoms and is bonded via a ring nitrogen atom to the penem radical, for example a corresponding aza-, diaza-, triaza- or tstraza-cycl ic radical of aromatic character or a corresponding dihydro radical, 107 2 a corresponding partially saturated monocyclic 6-membered heteroaryl radical having from 1 to 3 ring nitrogen atoms, such as a corresponding aza-, diaza- or triaza-cyclic radical, or a corresponding optionally partially saturated benzo, dibenzo, pyrido or pyrimido derivative of such a 5- or 6-membered radical, these radicals being unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lower alkylthio, phenyl thio, lower alkyl, hyd roxy-lower alkyl, lower alkanoyloxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyl oxy-lower alkyl, halo-lower alkyl, lower alkylthio-lower alkyl, optionally N-lower alkylated amino-lower alkyl, lower alkanoylamino-lower alkyl, amino~carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, sulpho-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower al kyleneamino , lower al kanoylamino , carboxy, lower alkoxycarbonyl, carbamoyl, N-mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho, sulphamoyl, phenyl optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, or cycloal kyl, nitro, imino, oxo and/or by oxido, Rj represents carboxy, esterified carboxy that can be cleaved under physiological conditions or protected carboxy R3', to optical isomers of compounds of the formula I, to mixtures of these optical isomers and to salts of compounds of the formula I having a salt-forming g roup. The invention relates more especially to compounds of the formula I in which Rj represents lower alkyl subtituted by hydroxy or by tri-lower al kyl silyl oxy, ^2 represents 1-pyrrolyl or dihydro-1-pyrrolyl optionally substituted by lower alkyl or by halogen, imidazol-1-yl optionally substituted by lower alkyl, 2107 -19- lower alkoxy, amino-lower alkyl, N-lower alkylated amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, halo-lower alkyl, sulpho-lower alkyl, lower alkylthio-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkanoylamino or by nitro, pyrazol-1-yl optionally substituted by lower alkyl, amino-lower alkyl, amino-carboxy-lower alkyl, amino or by nitro, 1,2,3-, 1,2,4- or 1,3,4-triazol-1-yl optionally substituted by lower alkyl, carboxy-lower alkyl or by phenyl, 1- or 2-tetrazolyl optionally substituted by lower alkyl, carboxy-lower alkyl, sulpho-lower alkyl, di-lower alkylamino-lower alkyl, amino or by optionally halo-substituted phenyl, dihydro-1-pyridyl that is unsubstituted or substituted by oxo and optionally additionally suLsLituted by halogen, dihydro-or tetrahydro-1-pyrimidyl that is unsubstituted or substituted by oxo and optionally additionally substituted by lower alkyl, amino, di-lower alkylamino and/or by carboxy, dihydro- or tetrahydro-1,2,4- or -1,3,6-triazin-1-yl, each of which is optionally substituted by lower alkyl, lower alkoxy, amino and/or by up to 2 oxo groups, indol-1-yl, benzimidazol-1-yl, benzotriazol-1-yl, pyridopyrrol-1-yl, pyridoimidazol-1 -yl, or pyrimido-, d ihydropyrimido- or tstrahydro-pyrimido-imidazol-1-yl each optionally substituted by amino, imino and/or by oxo, or pyrimido-, dihydropyrimido- or tetrahydropyrimido-1,2,3-triazol-1-yl each optionally substituted by amino, imino and/or by oxo, and R3 represents carboxy, 4-nitrobenzyloxycarbonyl, lower alkenyloxycarbonyl, or ethoxycarbonyl substituted in the 2-position by lower 2 10 7 2 3 - 20 - alkylsulphonyl, cyano or by tri-lower alkylsilyl, or an esterified carboxy group that can be cleaved under physiological conditions, to optical isomers of compounds of the formula I, to mixtures of these optical isomers and to salts of such compounds of the formula I having a salt-forming group. The invention relates especially to compounds of the formula I in which Rj represents lower alkyl substituted in the a-position by hydroxy, R2 represents pyrrol-1-yl that is unsubstituted or substituted by lower alkyl or by halogen, pyrazol-1-yl that is unsubstituted or substituted by lower alkyl or by amino-lower alkyl, imidazol-1-yl that is unsubstituted or substituted by lower alkyl, lower alkoxy, amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, halo-lower alkyl, lower alkylthio-lower alkyl, amino or by nitro, 1,2,4- or 1,3,4-triazol-1-yl that is unsubstituted or substituted by lower alkyl, 1- or 2-tetrazolyl each of which is unsubstituted or substituted by lower alkyl, amino or by phenyl, indol-l-yl, benz-imidazol-l-yl, benzotriazol-l-yl, lH-pyrrolo(2,3—b)-pyrid-l-yl, lH-imidazo(4,5-b)-pyrid-l-yl or purin-1-yl, and R^ represents carboxy or esterified carboxy that can be cleaved under physiological conditions, such as lower alkanoyloxymethoxycarbonyl or 1-lower alkoxycarbonyloxy-lower alkoxycarbonyl, to optical isomers of compounds of the formula I, to mixtures of these optical isomers and to salts, especially pharmaceutically acceptable salts, of such compounds of the formula I containing a salt-forming g roup. - 21 - 2 1 07 The invention relates very especially to compounds of the formula I in which Rj represents hydroxymethyl or 1-hydroxyethyl, R2 represents pyrrol-1-yl, imidazol-1-yl that is unsubstituted or substituted by lower alkyl, lower alkoxy, amino or by amino-lower alkyl, pyrazol-1-yl that is unsubstituted or substituted by lower alkyl or by amino-lower alkyl, 1,2,4-triazol-1-yl, or tetrazol-1-yl that is unsubstituted or substituted by amino, and R^ represents carboxy or esterified carboxy that can be cleaved under physiological conditions, such as lower alkanoyloxy-methoxycarbonyl or 1-lower alkoxycarbonyloxy-lower alkoxycarbonyl, to optical isomers, especially the (1R)-isorner, of compounds of the formula I in which Rj represents 1-hydroxyethyl, to mixtures of these optical isomers and to salts, especially pharmaceutically acceptable salts, of compounds of the formula I. The invention relates chiefly to compounds of the formula I in which Rj represents hydroxymethyl or (1R)-1-hydroxyethyl, R2 represents imidazol-1-yl that is unsubstituted or substituted by lower alkyl or by amino-lower alkyl, and R^ represents carboxy or esterified carboxy that can be cleaved under physiological conditions, such as lower alkanoyloxymethoxy-carbonyl or 1-lower alkoxycarbonyloxy-lower alkoxycarbonyl, and to salts, especially pharmaceutically acceptable salts, of compounds of the formula I. The invention relates especially to the compounds of the formula I mentioned in the Examples and to the salts thereof, especially pharmaceutically acceptable salts. The compounds of the present invention can be manufactured by processes known per se. The novel compounds are manufactured, for example, as follows: - 22 - 2 1 07 a) an ylide compound of the formula z •C—R, -N (II) jP I V in which Rj and R2 have the meanings given under formula I and R3' represents a protected carboxy group, Z represents oxygen or sulphur and X® represents either a tri-substituted phosphonio group or a di-esterified phosphono group together with a cation, is cyclised, or b) a compound of the formula R. .S— C— R_ 1- + II 2 f z (III), N =0 I V in which Rj and R2 have the meanings given under formula I, Z has the meaning given under formula II and R3' represents a protected carboxy group, is treated with an organic compound of trivalent phosphorus, or c) a compound of the formula RL (X), - 23 - 2 10723 in which R j has the meaning given under formula I, R3' represents a protected carboxy group and Y represents a group that can be replaced by nucleophilic reaction, is reacted with a compound that introduces the radical R2, and, if desired or necessary, in a resulting compound of the formula I a protected hydroxy group in the radical Rj is converted into a free hydroxy group, and/or, if desired, in a resulting compound of the formula I a protected carboxy group R3' is converted into a free carboxy group, into an esterified carboxy group that can be cleaved under physiological conditions or into a different protected carboxy group R3', or a free carboxy group R3 is converted into an esterified carboxy group that can be cleaved under physiological conditions or into a protected carboxy group R3', and/or, if desired, other protected functional groups contained in the radical R2 are converted into free functional groups, and/or, if desired, in a resulting compound of the formula I a radical R2 is converted into a different radical R2, and/or, if desired, a resulting compound having a salt-forming group is converted into a salt, or a resulting salt is converted into a free compound or into a different salt, and/or, if desired, a resulting mixture of isorr.eric compounds is separated into the individual isomers. In the starting compounds of the formulae II, III and X, functional groups, such as a free hydroxy group in the radical Rj and other functional groups contained in the radical R2, are preferably protected by conventional protecting groups, for example by those mentioned hereinbefore. a) Cyclisation of the compound of the formula II The group X® in a starting material of the formula II is one of the phosphonio or phosphono groups customarily used in Wittig condensation reactions, especially a triaryl-, for example triphenyl-, or tri-lower alkyl-, for example tri-n-butyl-phosphonio group, or a phosphono group di-esterified by lower alkyl, for example ethyl, the symbol X® in the case of the phosphono group including in addition the cation of a strong base, especially a suitable metal ion, such as an alkali metal ion, for example a lithium, sodium or potassium ion. Preferred as the group X®is, on the one hand, triphenylphosphonio and, on the other hand, diethylphosphono together with an alkali metal ion, for example a sodium ion. In phosphonio compounds of the formula II, the negative charge is neutralised by the positively charged phosphonio group. In phosphono compounds of the formula Ti, the negative charge is neutralised by the cation of a strong base, which, depending upon the method of manufacture of the phosphono starting material, may be, for example, an alkali metal ion, for example a sodium, lithium or potassium ion. The phosphono starting materials are therefore used in the form of salts in the reaction. Cyclisation may take place spontaneously, that is to say during the manufacture of the starting materials, or may be effected by heating, for example in a temperature range of approximately from 30° to 160°c, preferably from approximately 50° to approximately 100°C. The reaction is preferably carried out in a suitable inert solvent, such as an - 25 - 2 10723 ~ aliphatic, cycloaliphatic or aromatic hydrocarbon, for example cyclohexane, benzene or toluene, a halogenated hydrocarbon, for example methylene chloride, an ether, for example diethyl ether, a cyclic ether, for example dioxan or tetrahydrofuran, a carboxyl ic acid amide, for example dimethyl formamide, a di-lower alkyl sulphoxide, for example dimethyl sulphoxide, or a lower alkanol, for example ethanol, or in a mixture thereof, and, if necessary, in an inert gas atmosphere, for example a nitrogen atmosphere. b) Cyclisation of the compound of the formula III An organic compound of trivalent phosphorus is derived, for example, from phosphorous acid and is especially an ester thereof with a lower alkanol, for example methanol or ethanol, and/or an optionally substituted aromatic hydroxy compound, for example phenol or pyrocatechol, or an amide ester thereof of the formula P (0Ra) 2-N (R^) 2 in which each of Ra and R^, independently of the other, represents lower alkyl, for example methyl, or aryl, for example phenyl. Preferred compounds of trivalent phosphorus are tri-alkyl phosphites, for example trimethyl phosphite or triethyl phosphite. The reaction is preferably carried out in an inert solvent, such as an aromatic hydrocarbon, for example benzene or toluene, an ether, for example dioxan or tetrahyd rof uran, or a halogenated hydrocarbon, for example methylene chloride or chloroform, at a temperature of approximately from 20° to 30°C, preferably at from approximately 40° to approximately 60°C, one molar equivalent of a compound of the formula III being reacted with two molar equivalents of the phosphorus compound. Preferably, the compound of the - 26 - ?3 formula III is placed in an inert solvent and the phosphorus compound, preferably dissolved in the same inert solvent, is added dropwise over a prolonged period, for example over a period of from 2 to 4 \ hours. I. In a preferred embodiment of the process, the ' starting material of the formula III is manufactured as described hereinbelow and, without being isolated from the reaction mixture, is reacted with the organic k ' t compound of trivalent phosphorus, the end products of the formula I being formed. c) Introduction of the radical Rp In a compound of the formula X, a group Y that can be replaced by nucleophilic reaction is, for example, a radical of the formula -S(0)-R^ in which R4 represents, for example, lower alkyl, for example methyl or ethyl, cycloalkyl, for example cycloper.tyl or cyclohexyl, or aralkyl, for example benzyl, or is reactive esterified hydroxy, such as lower alkanoyloxy optionally substituted by halogen, for example acetoxy, lower alkanesulphonyloxy, for example methanesulphonyloxy, benzenesulphonyloxy optionally substituted by lower alkyl, such as methyl, or by halogen, such as bromine, for example benzenesulphonyloxy, D-methyl- or £-bromo-benzenesulphonyloxy, or is a radical of the formula -0-P0(OR^)2 in which R5 represents, for example, lower alkyl, such as methyl or ethyl. Suitable compounds that introduce the radical R2 are, for example, compounds of the formula R2-H *n which the hydrogen atom is bonded to the nitrogen atom of the azaheterocyclyl radical R2 that is to be joined to the penem residue, or a salt, such as an alkali metal salt, for example the lithium, sodium or - 27 - 2 1 0723 potassium salt, thereof, or compounds of the formula R2-Si(Rg)3 in which Rg represents especially lower alkyl, for example methyl. The reaction of the compound of the formula X with the compound that introduces the radical R2 is preferably carried out in an inert solvent, for example dimethylformamide, dimethyl sulphoxide, acetonitrile, water or mixtures thereof, at a temperature of from approximately -50° to approximately +50°C, especially at from approximately -20° to approximately +20°C, it being advantageous for the reaction with compounds of the formula R2-H to be carried out in the presence of equimolar amounts of a base, such as an organic base, for example diisopropylethyl-amine, triethylamine or pyridine, or an inorganic base, for example sodium bicarbonate or potassium carbonate. The starting compounds of the formula X are known or can be manufactured according to known processes. It is preferable to use those starting materials of the formulae II, III and X which result in the compounds of the formula I mentioned at the beginning as being especially preferred. In a resulting compound of the formula I in which one or more functional groups are protected, these groups, for example protected carboxy, hydroxy, amino and/or sulpho groups, may be freed, optionally in stages or simultaneously, in a manner known per se by means of solvolysis, especially hydrolysis, alcoholysis or acidolysis, or by means of reduction, especially hydrogenolysis or chemical reduction. In a compound of the formula I obtainable according to the process in which R3 represents a protected carboxy group and/or in which the radical R2 contains protected carboxy as substituent, the protected carboxy group can be freed in a manner known per se. Thus, - 28 - 1 4 if tert.-lower alkoxycarbonyl, or lower alkoxycarbonyl substituted in the 2-position by a tri-substituted silyl group or in the 1-position by lower alkoxy, or optionally substituted diphenylmethoxycarbonyl can be converted into free carboxy, for example, by treatment with a carboxylic acid, such as formic acid or trifluoroacetic acid, optionally with the addition of a nucleophilic compound, such as phenol or anisole. Optionally substituted benzyloxycarbonyl can be cleaved, for example, by means of hydrogenolysis, that is to say by treatment with hydrogen in the presence of a metallic hydrogenation catalyst, such as a palladium catalyst. Furthermore, suitably substituted benzyloxycarbonyl, such as 4-nitrobenzyloxycarbonyl, can also be converted into free carboxy by means of chemical reduction, for example by treatment with an alkali metal dithionite, for example sodium dithionite, or with a reducing metal, for example tin, or a reducing metal salt, such as a chromium(ll) salt, for example chromium(Il) chloride, customarily in the presence of a hydrogen-yielding agent that together with the metal is capable of producing nascent hydrogen, such as a suitable carboxylic acid, for example a lower al kanecarboxyl ic acid optionally substituted, for example, by hydroxy, for example acetic acid, formic acid or glycolic acid, or an alcohol or thiol, it being preferable to add water. The removal of an allyl protecting group can be effected, for example, by reaction with a palladium compound, for example tetraki s (tr iphenylphosphine) -palladium, in the presence of triphenylphosphine and with the addition of a carboxylic acid, for example 2-ethylhexanoic acid, or a salt thereof. By treatment with a reducing metal or metal salt, as described above, it is also possible to convert 2-halo-lower - 29 - ? alkoxycarbonyl (optionally after converting a 2-bromo-lower al koxycarbonyl group into a corresponding 2-iodo-lower al koxycarbonyl group) or aroylmethoxycarbonyl into free carboxy, whilst aroylmethoxycarbonyl can be cleaved likewise by treatment with a nucleophilic, preferably salt-forming, reagent, such as sodium thio-phenolate or sodium iodide. Substituted 2-silylethoxy carbonyl can be converted into free carboxy also by treatment with a salt of hydrofluoric acid that yields the fluoride anion, such as an alkali metal fluoride, for example sodium fluoride, in the presence of a macrocyclic polyether ("Crown ether") or with a fluoride of an organic quaternary base, such as tetra-lower alkyl ammonium fluoride, for example tetrabutyl-ammonium fluoride. Carboxy esterified by an organic silyl or stannyl group, such as tri-lower alkylsilyl or tri-lower alkylstannyl, can be freed in customary manner by solvolysis, for example by treatment with water or an alcohol. A lower alkoxycarbonyl group substituted in the 2-position by lower alkylsulphonyl or cyano can be converted into free carboxy, for example, by treatment with a basic agent, such as an alkali metal or alkaline earth metal hydroxide or carbonate, for example sodium or potassium hydroxide or sodium or potassium carbonate. On the other hand, it is also possible for compounds of the formula I in which R3 represents carboxy to be converted into compounds of the formula I in which R3 represents a protected carboxy group, especially an esterified carboxy group, or an esterified carboxy group that can be cleaved under physiological conditions. Thus, the free carboxy group can be esterified, for example, by treatment with a suitable diazo compound, such as a diazo-lower alkane, for example diazomethane, or a phenyldiazo-lower • 30 - •7 « alkane, for example diphenyldiazomethane, if necessary in the presence of a Lewis acid, such as, for example, boron trifluoride, or by reaction with an alcohol suitable for ester ification in the presence of an estarifying agent, such as a carbodiimide, for example dicyclohexyl carbodiimide, and carbonyldiimidazole. Esters can also be manufactured by reaction of a salt of the acid, which salt is optionally produced in situ, with a reactive ester of an alcohol and a strong inorganic acid, such as sulphuric acid, or a strong organic sulphonic acid, such as 4-toluenesulphonic acid. Furthermore, acid halides, such as chlorides (manufactured, for example, by treatment with oxalyl chloride), activated esters (formed, for example, with N-hydroxynitrogen compounds, such as N-hydroxysuscin-imide) , or mixed anhydrides (obtained, for example, with haloformic acid lower alkyl esters, such as chloroformic acid ethyl ester or chloroformic acid isobutyl ester, or with haloacetic acid halides, such as trichloroacetyl chloride) can be converted into esterified carboxy groups by reaction with suitable alcohols, optionally in the presence of a base, such as pyrid ine. In a compound of the formula I having an esterified carboxy group, this group can be converted into a different esterified carboxy group: for example 2-chioroethoxycarbonyl or 2-bromoethoxycarbonyl may be converted by treatment with an iodine salt, for example sodium iodide, into 2-iodoethoxycarbonyl . Furthermore, in compounds of the formula I that contain a carboxy group protected in esterified form, the carboxy-protecting group can be removed as described above, and a resulting compound of the formula I having a free carboxy group or a salt thereof can be converted by reaction with the reactive ester of a corresponding alcohol into a compound of the formula I in which R3 represents an esterified carboxy group that can be cleaved under physiological conditions. In compounds of the formula I obtainable according to the process in which the radical Rj and/or the radical R2 contains protected hydroxy as substituent, the protected hydroxy group can be converted into a free hydroxy group in a manner known per se. For example, a hydroxy group protected by a suitable acyl group or an organic silyl or stannyl group is freed in the same manner as a correspondingly protected amino group (see below); a tri-lower alkylsilyl group is removed, for example, also with tetra-butylammonium fluoride and acetic acid (under these conditions carboxy groups protected by tri-substituted silylethoxy are not cleaved). A 2-halo-lower alkyl group and an optionally substituted benzyl group are removed by reduction. In a compound of the formula I obtainable according to the invention having a protected amino group, this group may be converted into the free amino group in a manner known per se, for example, depending on the nature of the protecting group, preferably by means of solvolysis or reduction. For example, 2-halo-lower alkoxycarbonylamino (optionally after converting a 2-bromo-lower alkoxycarbonylamino group into a 2-iodo-lower alkoxycarbonylamino group), aroylmethoxycarbonylamino or 4-nitrobenzyloxycarbonylamino can be cleaved by treatment with a suitable chemical reducing agent, such as zinc in the presence of a suitable carboxylic acid, such as aqueous acetic acid, or by catalysis with hydrogen in the presence of a palladium catalyst. Aroylmethoxycarbonylamino may be cleaved also by treatment with a nucleophilic, preferably salt-forming, reagent, such as sodium thiophenolate, and 4-nitrobenzyloxycarbonylamino may be cleaved also by treatment with an alkali metal dithionite, for example sodium dithionite. Optionally substituted benzyloxycarbonylamino may be cleaved, for example, by means of hydrogenolysis, that is to say by treatment with hydrogen in the presence of a suitable hydrogenation catalyst, such as a palladium catalyst, and allyloxycarbonylamino by reaction with a palladium compound, for example tetrakis(triphenylphosphine)-palladium, in the presence of triphenylphosphine and treatment with a carboxylic acid, for example 2-ethylhexanoic acid, or with a salt thereof. An amino group protected by an organic silyl or stannyl group can be freed, for example, by means of hydrolysis or alcoholysis, and an amino group protected by 2-halo-lower alkanoyl, for example 2-chloroacetyl, can be freed by treatment with thiourea in the presence of a bass or with a thiolate salt* such as an alkali metal thiolate, of thiourea and subsequent solvolysis, such as alcoholysis or hydrolysis, of the resulting condensation product. &n amino group protected by 2-substituted silylethoxycarbonyl can be converted into the free amino group by treatment with a salt of hydrofluoric acid that yields fluoride anions, such as an alkali metal fluoride, for example sodium fluoride, in the presence of a macrocyclic polysther ("Crown ether") or with a fluoride of an organic quaternary base, such as tetra-lower alkylammonium fluoride, for example tetraethylammonium fluoride. An amino group protected in the form of an azido or nitro group is converted into free amino, for example, by reduction, for example by catalytic hyd rogenation with hydrogen in the presence of a hydrogenation catalyst, such as platinum oxide, palladium or Raney nickel, or by 1 . - / • ... • . 2 1 07 - 33 - treatment with zinc in the presence of an acid, such as acetic acid. An amino group protected in the form of a phthalimido group can be converted into the free amino group by reaction with hydrazine, r^rthennore, an aryl-thioamino group can be converted into amino by treatment with a nucleophilic reagent, such as sulphurous acid. A protected, especially esterified, sulpho group is freed analogously to a protected carboxy group. In compounds of the formula I, it is also possible to convert a radical R2 into a different radical r2. Thus, for example, in compounds of the formula I in which the radical R2 is substituted by a carboxy group, this carboxy group can be converted by processes known per se into a functionally modified carboxy group, such as into an esterified carboxy group or into optionally substituted carbamoyl. For example, by reacting a compound of the formula I in which R2 represents azaheterocyclyl substituted by carboxy with an alcohol, especially a lower alkanol, there is obtained a compound of the formula I in which R2 represents azaheterocyclyl substituted by esterified carboxy, especially by lower alkoxycarbonyl, it being preferable to carry out the reaction in the presence of a suitable condensation agent, for example a carbodiimide, or to remove by means of azeotropic distillation the water that is formed. On the other hand, carboxy groups at the radicals R2 can also be converted into reactive functional derivatives, such as mixed anhydrides, for example acid halides, or activated esters, which can then be converted into correspondingly esterified or amidated carboxy groups by reaction with an alcohol, for example lower alkanol, ammonia or a primary or secondary amine, for example a 2 107 - 34 - lower alkvlamine or di-lower alkylamine, it being preferable when using mixed anhydrides to carry out the reaction in the presence of an acid-binding agent, such as an aromatic or tertiary amine or an alkali metal or alkaline earth metal carbonate. If a heteroaryl radical R2 has a hydroxy group, the latter can be etherified in customary manner. The reaction to form the corresponding lower alkyl heteroaryl ethers is effected, for example, in the presence of bases, such as alkali metal hydroxides or carbonates, for example sodium hydroxide or potassium carbonate, with the aid of di-lower alkyl sulphates or lower alkyl halides, or with diazo-lower alkanes, or, in the presence of a dehydrating agent, for example dicyclohexyl carbodiimide, with the aid of lower alkanols. In addition, hydroxy can be converted into esterified hydroxy, for example lower alkanoyloxy, for example by reaction with the reactive derivative of a corresponding lower al kanecarboxyl ic acid, for example acetic acid, such as an anhydride thereof, for example the symmetric anhydride thereof, or a mixed anhydride with a hydrohalic acid, if necessary in the presence of a basic condensation agent, such as an alkali metal hydroxide or carbonate, or a nitrogen base, for example pyridine. The conversion of lower alkanoyloxy into hydroxy is effected, for example, by means of alcoholysis or, preferably, hydrolysis, for example by means of base-catalysed hydrolysis, for example in the presence of sodium hydroxide. In compounds of the formula I in which R2 represents azaheterocyclyl substituted by amino, the amino group can be converted into a substituted amino group, for example a lower alkylamino, di-lower alkylamino, lower alkyleneamino or lower alkanoylamino group. The conversion into a lower alkylamino or di- lower alkylamino group is effected, for example, by reaction with a reactive esterified lower alkanol, for example a lower alkyl halide or sulphonate, in the presence of a basic condensation agent, such as a hydroxide or carbonate of an alkali metal or alkaline earth metal or a heteroaromatic nitrogen base, for example pyridine. In analogous manner, amino can be converted into lower alkyleneamino by treatment with a lower alkylene dihalide or disulphonate and into lower alkanoylamino by treatment with a reactive functional derivative of a lower al kanecarboxyl ic acid, for example the corresponding carboxylic acid halide. Compounds of the formula I having a substitutable ring nitrogen atom in the radical R2 can be converted in the same manner into compounds of the formula I containing in the radical R2 a ring nitrogen atom substituted by an optionally substituted lower alkyl radical. The novel compounds of the formula I that can be manufactured with the aid of the mentioned reactions may therefore contain in the radical R2 a correspondingly substituted secondary, tertiary or alternatively quaternary, that is to say positively charged, nitrogen atom. Salts of compounds of the formula I having salt-forming groups may be manufactured in a manner known per se. Thus, salts of compounds of the formula I having a free carboxy or sulpho group can be formed, for example, by treatment with metal compounds, such as alkali metal salts of suitable organic carboxylic acids, for example the sodium salt of a-ethyl-caproic acid, or with inorganic alkali metal or alkaline earth metal salts, for example sodium bicarbonate, or with ammonia or with a suitable organic amine, it being preferable to use stoichiometric amounts or only a small excess of the salt-forming •v a - 36 - agent. Acid addition salts of compounds of the formula I are obtained in customary manner, for example by treatment with a suitable acid or a suitable anion exchange reagent. Internal salts of compounds of the formula I can be formed, for example, by neutralising salts, such as acid addition salts, to the isoelectric point, for example with weak bases, or by treatment with ion exchangers. Salts can be converted into the free compounds in customary manner; metal and ammonium salts, for example by treatment with suitable acids, and acid addition salts, for example by treatment with a suitable basic agent. Resulting mixtures of isomeric compounds can be separated into the individual isomers according to methods known per se. For example, a resulting racemate is allowed to react with an optically active auxiliary, the resulting mixture of two diastereoisomeric compounds is separated with the aid of suitable physico-chemical methods (for example by fractional crystallisation, adsorption chromatography) and the individual diastereoisomeric compounds are then separated into the optically active compounds. Racemates that are especially suitable for separation into the antipodes are those which contain an acidic group, such as, for example, racematas of compounds of the formula I in which R3 represents carboxy. These acidic racemates can be reacted with optically active bases, for example esters of optically active amino acids, or (-)-brucine, (+)-quinidine, (-)-quinine, (+)-cinchonine, (+)-dehydroabietylamine, (+)- and (-)-ephedrin, (+)- and (-)-l-phenylethylamine or their N-mono- or N,N-di-alkylated derivatives, to form mixtures consisting of two diastereoisomeric salts. In racemates that contain carboxy groups, the - 37 - 2 1 0""> 3 *» ' carboxy group can also be esterified by an optically active alcohol, such as (-)-menthol, (+)-borneol, (+)-or (-)-2-octanol, whereupon, when isolation of the desired diastereoisomer is complete, the carboxy group is freed. For separation of the racemates, a hydroxy group present can also be esterified by optically active acids or reactive functional derivatives thereof, diastereoisomeric esters being formed. Such acids are, for example, (-)-abietic acid, £(+)- and L(-)-malic acid, N-acylated optically active amino acids, ( + )- and (-)-camphanic acid, ( + )- and (-)-ketopinic acid, M+)-ascorbic acid, ( + )-camphoric acid, (+)-camphor-1 0-sulphonic acid(8), (+)- or (-)-a-bromocamphor-7P sulphonic acid, l)(-)-quinic acid, D(-)-isoascorbic acid, £(-)- and M+)-mandel ic acid, (+)-1-menthoxy-acetic acid, JD(—) — and M+)-tartaric acid and the di-O-benzoyl and di-0-£-toluoyl derivatives thereof. By reaction with optically active isocyanates, such as with (+)- or (-)-l-phenylethyl isocyanate, it is possible to convert compounds of the formula (I) in which R3 represents protected carboxy and Rj represents / lower alkyl substituted by hydroxy into a mixture of f diastereoisomeric urethanes. Basic racemates, for example compounds of the ' formula I in which the radical R2 is substituted by i amino, can form diastereoisomeric salts with the mentioned optically active acids. The splitting up of the separated diastereoisomers into the optically active compounds of the formula I is also effected according to customary methods. The acids or the bases are freed from the salts, for example, by treatment with acids or bases that are stronger than those originally used. The desired optically active compounds are obtained from the esters r - ! i 2 1 - 38 and urethanes, foe example, after alkaline hydrolysis or after reduction with a complex hydride, such as lithium aluminium hydride. A further method of separating the racemates comprises chromatography on optically active adsorption layers, for example on cane sugar. According to a third method, the racemates can be dissolved in optically active solvents and the more sparingly soluble optical antipode can be crystallised out. A fourth method utilises the different reactivities of the optical antipodes with respect to biological material, such as micro-organisms or isolated enzymes. According to a fifth method, the racemates are dissolved and one of the optical antipodes is crystallised out by inoculation with a small quantity of an optically active product obtained according to the above methods. The separation of the racemates into the optical antipodes can be carried out at any stage of the process, that is to say, for example, even at the stage of the starting compounds of the formula II or III or at any stage of the process for the manufacture of the starting compounds of the formula II or III that is described hereinafter. In all subsequent conversions of resulting compounds of the formula I, those reactions are preferred which take place under alkaline or, especially, neutral conditions. The process also includes those embodiments according to which compounds formed as intermediates are used as starting materials and the remaining process steps are carried out with them, or the process is interrupted at any stage. Furthermore, starting • v - v~' - • 'V „ W - .. * t,„ • '- ~- -m*»- -- -.— ^-—'- - ?10723 - 39 - materials can be used in the form of derivatives or can be manufactured _in situ, optionally under the reaction conditions. The starting compounds of the formulae II and III can be manufactured as indicated in the following reaction scheme I. / ' /•»' • ' * Jr-^ - 40 - Reaction scheme I 2 1072 w \ / / z II S-C-R, Stage 1 ■ NH (IV) Stage 3 Z I S-C-R. -N \ CH~~^X R. (VI) Stage 4 % k. / z I! S-C-R, .NH (V) Stage 2 Ru AS-C-R, II 2 7. -N, •C=0 V (III) ^^SM Stage 5 ^ ^(P -X® (II) 0^ ■ N V o' -P I V (VII) 210723 - - 41 - Stage 1 A thioazetidinone of the formula V is obtained by reacting a compound of the formula IV with a compound that introduces the radical -S-C(*Z)-R2. In a starting material of the formula IV, W is a nucleofugal radical that can be replaced by the group -S-C(=Z)-R2. Such radicals W are, for example, acyloxy radicals, sulphonyl radicals Rq-S02- in which RQ is an organic radical, or azido or halogen. In an acyloxy radical W, acyl is, for example, the radical of an organic carboxylic acid and represents, for example, lower alkanoyl, for example acetyl or propionyl, optionally substituted benzoyl, for example benzoyl or 2,4-dinitrobenzoyl, or phenyl-lower alkanoyl, for example phenylacetyl. In a sulphonyl radical Rq-S02-, Rq is, for example, lower alkyl optionally substituted by hydroxy, such as methyl, ethyl, 2-hydroxyethyl, 1-hydroxyprop-2-yl or 1-hydroxyzine thyl prop-2-yl, benzyl or optionally substituted phenyl, such as phenyl, 4-bromophenyl or 4-methylphenyl. A halogen radical W is, for example, bromine, iodine or, especially, chlorine. W is preferably methyl- or 2-hydroxyethyl-sulphonyl, acetoxy or chlorine. A compound that introduces the radical -S-C(=Z)-R2 is, for example, an acid of the formula R2-C(=Z)-SH or especially a salt, for example an alkali metal salt, such as the sodium or potassium salt, thereof. The substitution can be carried out in an organic solvent, such as in a lower alkanol, for example methanol or ethanol, a lower alkanone, for example acetone, a lower alkanecarboxylic acid amide, for example dimethylformamide, a cyclic ether, for example tetrahydrofuran or dioxan, or in a similar inert solvent. The reaction is customarily carried out * 210723 - 42 - at room temperature but may also be carried out at elevated or reduced temperature, for example at from approximately 0° to approximately 40°C. The reaction can be accelerated by adding a salt of hydriodic acid or of thiocyanic acid, for example an alkali metal salt, such as the sodium salt. The group -S-C(=Z)-R2 being introduced is directed by the radical Rj preferentially into the trans-position. It is therefore possible to use (3S,4R)- and (3S,4RS)-configured starting compounds of the formula IV. Although predominantly the trans-isomers are formed, occasionally small amounts of the cis-isomer may also be produced. The cis-isomers are separated off according to conventional methods, as described above, especially by chromatography and/or by crystallisation. Suitable starting compounds of the formula IV are known, for example from European Specification No. 82113 [cf. Chemical Abstracts 99, 139637a (1983)], British Patent Specification Nr. 2104509 and British Patent Specification Nr. 2048261, or can be manufactured in an analogous manner. They can also be manufactured according to the processes described in the Examples. Stage 2 A starting compound of the formula (III) is obtained by treating an azetidinone of the formula (V) with an acid of the formula R^'-COOH or especially with a reactive derivative, such as an ester or acid halide, for example the acid chloride, thereof at a temperature of from 20° to 80°C, preferably from 40° to 60°C, in an inert solvent, such as one of those mentioned for the reaction of compounds of the formula III to form compounds of the formula I. Whert'v -3SEP1967 \ 1 07 - 43 - using an acid halide, the operation is preferably carried out in the presence of an acid-binding agent, such as a tertiary aliphatic amine, for example tri-ethylamine, an aromatic amine, for example pyridine, or especially an alkali metal or alkaline earth metal carbonate or bicarbonate, for example potassium carbonate or calcium carbonate. Stage 3 Compounds of the formula VI in which XQ represents a reactive esterified hydroxy group, especially halogen, for example chlorine or bromine, or organic sulphonyloxy, for example lower alkanesulphonyloxy, such as methanesulphonyloxy, or arenesulphonyloxy, for example benzene- or 4-methylbenzene-sulphonyloxy, are manufactured by reacting a compound of the formula V with a glyoxylic acid compound of the formula OHC-Rj' or with a suitable derivative thereof, such as a hydrate, hemihydrate or hemiacetal, for example a hemiacetal with a lower alkanol, for example methanol or ethanol, and, in a resulting compound of the formula VI in which XQ represents hydroxy, converting the hydroxy group into a reactive esterified hydroxy group. The compounds of the formula VI are usually obtained in the form of a mixture of the two isomers [with respect to the -CH (R^ ' —XQ grouping]. It is also possible, however, to isolate the pure isomers thereof, for example by chromatography. The addition of the glyoxylic acid ester compound to the nitrogen atom of the lactam ring in the compound of the formula V is effected at room temperature or, if necessary, while heating, for example at approximately 100°C, and in the absence of an actual condensation agent. When using the hydrate of the glyoxylic acid compound, water is formed which, if necessary, is 2 10723 - 44 - removed by distillation, for example azeotropic distillation, or by using a suitable dehydrating agent, such as a molecular sieve. The operation is preferably carried out in the presence of a suitable solvent, such as, for example, dioxan, toluene or dimethylformamide, or a solvent mixture and, if desired or necessary, in the atmosphere of an inert gas, such as nitrogen. The conversion of a hydroxy group X0 into a reactive esterified hydroxy group XQ in a compound of the formula VI is carried out by treatment with a suitable esterification agent, for example with a thionyl halide, for example the chloride, a phosphorus oxyhalide, especially the oxychloride, a halo-phosphonium halide, such as triphenylphosphonium dibromide or dichloride, or a suitable organic suiphonic acid halide, such as the chloride, preferably in the presence of a basic agent, especially an organic basic agent, such as an aliphatic tertiary amine, for example triethylamine or diisopropylamine, or a heterocyclic base of the pyridine type, for example pyridine or collidine. The operation is preferably carried out in the presence of a suitable solvent, for example dioxan or tetrahydrofuran, or a solvent mixture, if necessary while cooling, for example at from approximately -30° to approximately 30°C, and optionally in the atmosphere of an inert gas, such as n itrogen. Stage 4 The starting material of the formula (II) is obtained by treating a compound of the formula (VI) with a suitable phosphine compound, such as a tri-lower alkylphosphine, for example tri-n-butylphosphine, or a triarylphosphine, for example triphenylphosphine, or with a suitable phosphite compound, such as a tri- ? 07 - 45 - lower alkyl phosphite, for example triethyl phosphite, or an alkali metal di-lower alkyl phosphite, for example an alkali metal diethyl phosphite, and in a x. resulting compound of the formula (II) the radical R2 is optionally replaced by a different radical R2. The conversion of the compound of the formula (VI) into the compound of the formula (II) is preferably - * carried out in the presence of a suitable inert * ' solvent, such as a hydrocarbon, for example cyclohexane or benzene, or an ether, for example dioxan, or a solvent mixture. Depending upon the reactivity, the operation is carried out while cooling or at elevated temperature, at approximately from -10° to +100°C, preferably at approximately from 20° to 80°C, and/or in the atmosphere of an inert gas, such as j nitrogen. In order to prevent oxidative processes taking place, catalytic amounts of an antioxidant, for example hydroquinone, can be added. The reaction is customarily carried out in the presence of a basic agent, such as an organic base, for example an amine, such as triethylamine, diisopropyl-ethylamine, pyridine, lutidine or "polystyrene Hiinig base", or an inorganic base, for example an alkali metal carbonate, for example sodium or potassium carbonate, the initially produced phosphonium salt of the formula „ N 0^ ^CH-X' V (Ha) in which X' represents a phosphono group or a phos- phonio group together with an anion, which, depending on the meaning of the radical XQ, may be, for example, chloride, being converted into the ylide starting material of the formula II. It is also possible, however, to carry out the reaction in the absence of a base and to isolate a compound of the formula (Ila) , especially a corresponding phosphono compound, and convert that compound into the starting material of the formula II iji situ during the manufacture of the end products of the formula (I). In a resulting compound of the formula (II) a radical R2 can be replaced by a different radical R2« For this purpose a compound of the formula (II) in which R2 is a readily replaceable azaheterocyclyl radical, for example optionally substituted imidazol-1-yl, 1, 2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,4-triazol-1-yl, tetrazol-1-yl or tetrazol-2-yl, is reacted with an excess, especially a three- to ten-fold excess, of a compound of the formula R2'-H in which R2' is an unsaturated azaheterocyclyl radical according to the present invention other than R2. The reaction is carried out in an inert solvent or solvent mixture, for example in a cyclic ether, for example dioxan, in acetonitrile or in dimethylform-amide, at room temperature or at slightly elevated or reduced temperature, for example at from approximately 10° to approximately 50°C. Stage 5 A compound of the formula (II) can furthermore be obtained by treating a mercaptide of the formula (VII), in which M represents a metal cation, with an acylating agent that introduces the radical R2-C(=Z)-. In the starting material of the formula (VII), the 2 10723 ^ - 47 - metal cation M is, for example, a cation of the formula M+ or M^+/2 in which M+ represents especially a silver cation and M^"1" represents especially the divalent cation of a suitable transition metal, for example copper, lead or mercury. An acylating agent that introduces the radical R2-C( = Z)- is, for example, the acid R2~C(=Z)-OH or especially a reactive functional derivative thereof, such as an acid halide, for example chloride or bromide, or an azide or anhydride thereof, or a compound of the formula S=C(R2)2 in which the azaheterocyclyl radical R2 is bonded via a ring nitrogen atom to the thiocarbonyl group. If a reactive functional derivative of the acid of the formula R2-C(=Z)-OH, for example the acid chloride, is used, the acylation is carried out in an inert solvent, such as a chlorinated hydrocarbon, for example methylene chloride, or an ether, for example diethyl ether or dioxan, at room temperature or while heating or cooling, for example in a temperature range of from approximately -50° to approximately +60°C, especially from approximately -30°C to approximately +20°C. The acylation with the aid of the thiocarbonyl compound of the formula S=C(R2> is effected in an inert solvent, for example a halogenated hydrocarbon, such as methylene chloride, a cyclic ether, such as tetrahydrofuran, or dimethylformamide, at room temperature or at reduced temperature, for example at from approximately -3 0° to approximately 30°C, especially at approximately from 0° to 20°C. The starting compounds of the formula (VII) can be manufactured, for example, by converting an azetidinone of the formula 210723 ^ - 48 - w (IV) NH by reaction with an alkali metal salt, for example the sodium salt, of a thio-lower alkanecarboxylic acid, for example thioacetic acid, or of triphenylmethyl mercaptan, into a compound of the formula W (VIII) "NH in which W represents triphenylmethylthio or lower alkanoylthio, for example acetylthio, converting this compound, analogously to the process described in reaction stages 3 and 4, into a compound of the formula W' • N. ^C0-X0 (IX) and reacting this in the presence of a base, for example pyridine or tri-n-butylamine, in a suitable solvent,, for example diethyl ether or methanol, with a salt of the formula MA in which M has the meaning given above but represents especially a silver cation, and A represents a customary anion that promotes the - ' J x*<- 2 10723 - - 49 - solubility of the salt MA in the chosen solvent, for example the nitrate, acetate or fluoride anion. Thiocarbonyl compounds o: the formula S=C (1*2)2 *s in which the radical R2 is bonded via a nitrogen atom to the thiocarbonyl group are known or can be manufactured by converting a compound of the formula R2~H, in which the hydrogen atom is bonded to a ring / nitrogen atom of the radical R2, with a strong i. • inorganic base, for example sodium hydride, into a salt, for example into the sodium salt of the formula Na+R2~, or with a tri-lower alkylhalosilane, for ! example trimethylchlorosilane, in the presence of a base, into the tri-lower alkylsilyl derivative, and reacting the latter with thiophosgene. The ylides of the formula II can be used directly ' (. in the cyclisation reaction for the manufacture of the end products of the formula I. It is also possible, however, in compounds of the formula II in which Rj is lower alkyl substituted by a protected hydroxy group, for example a protected hydroxy group that can readily be cleaved by hydrolysis, such as tri-substituted silyloxy, first to remove the hydroxy-protecting group and then to use the resulting compound of the formula II in which Rj represents lower alkyl substituted by hydroxy in the cyclisation reaction. When a readily replaceable radical R2 is replaced by an asymmetrically substituted azaheterocyclyl radical R2' having at least two nitrogen atoms or by an unsubstituted azaheterocyclyl radical having at least 3 nitrogen atoms, of which two are adjacent, in a compound of the formula II (cf. the comments relating to Stage 4 of Reaction Scheme I), or when a radical R2 is introduced into a compound of the formula X (cf. Process c) ), two isomeric products may be formed. Thus, for example, in the reaction of a r i - 50 - 2 1 07 compound of the formula II or a compound of the formula X with 4-methylimidazole or a salt thereof, a product having a 4-methyl- or a 5-methyl-imidazol-l-yl radical may be formed. The imidazol-1-ylpenem compounds manufactured according to the invention by reacting a corresponding intermediate with an imidazole substituted in the 4-position are homogeneous according to thin-layer chromatography, and, on the basis of spectroscopic data, probably have an imidazol-1-yl radical substituted in the 4-position (and not in the 5-position) . There are also steric reasons arguing in favour of the preferential formation of imidazol-1-ylpenem compounds substituted in the 4-position. Until definite evidence of the structure is available, for example by means of X-ray structural analysis, the possibility of the mentioned compounds containing an imidazol-1-yl radical substituted in the 5-position cannot, however, be entirely ruled out. In compounds of the formulae (II)-(VII), functional groups may be converted into protected functional groups, or protected functional groups may be converted into the free groups or into differently protected groups. Furthermore, in compounds of the formulae (II), (III), (V) and (VI), a radical R2 may be converted into a different radical R2. In these conversions it is possible, taking into consideration the other substituents present in the molecules, to use the same methods as those indicated in the corresponding conversions into the compounds of the formula (I). It is also possible to carry out the process described in Reaction Scheme I for the manufacture of compounds of the formulae (II), (III) and (V)-(VII) and the processes indicated for the manufacture of the end products of the formula (I) with optically inactive - 51 - 2 10723 compounds and to isolate the optically active compounds according to the present invention from a resulting diastereoisomeric mixture or racemate, as described above, at any desired stage of the process. The invention relates also to the novel starting compounds and to novel intermediates which are obtainable according to the process, such as those of the formulae (II), (III), (V)-(VII) and (IX), and to the processes indicated for the manufacture thereof. The starting compounds used and reaction conditions chosen are preferably those which result in the compounds described hereinbefore as being especially preferred. The compounds of the formula I have valuable pharmacological properties or can be used as intermediates for the manufacture of such compounds having valuable pharmacological properties. Compounds of the formula I in which Rj represents lower alkyl substituted by hydroxy, R2 has the meaning given under formula I and R3 represents carboxy or an esterified carboxy group that can be cleaved under physiological conditions, and pharmacologically acceptable salts of such compounds having salt-forming groups have anti-bacterial activity. For example, they are effective jji vitro against gram-positive and gram-negative cocci, for example Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Streptococcus faecalis, and against gram-negative rod-shaped bacilli, such as Enterobacteriaceae, Haemophilus influenzae and Pseudomonas aeruginosa, and anaerobes, for example Bacteroides sp., in minimum concentrations of from approximately 0.02 to approximately 8 ug/ml. In vivo, in the case of systemic infection of mice, for example by Staphylococcus aureus, on subcutaneous administration of •s 1 'U / - 52 - compounds according to the invention, EDjq values of from approximately 4.5 to approximately 100 mg/kg are obtained. The novel compounds can be used as orally or parenterally administrable antibacterial antibiotics, for example in the form of corresponding pharmaceutical preparations, for the treatment of infections. Compounds of the formula I in which at least one of the functional groups present is in protected form can be used as intermediates for the manufacture of the above-mentioned pharmacologically active compounds of the formula I. The pharmacologically acceptable compounds of the present invention can be used, for example, for the manufacture of pharmaceutical preparations that contain a therapeutically effective amount of the active ingredient together or in admixture with inorganic or organic, solid or liquid, pharmaceutically acceptable carriers that are suitable for oral or for parenteral, that is to say intramuscular, subcutaneous or intraperitoneal, administration. For oral administration there are used tablets or gelatine capsules that contain the active ingredient together with diluents, for example lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine, and lubricants, for example silica, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol. Tablets also contain binders, for example magnesium aluminium silicate, starches, such as corn, wheat, rice or arrowroot starch, gelatine, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone, and, if desired, disintegrators, for example starches, agar, alginic acid or a salt thereof, such as sodium alginate, and/or effervescent mixtures 2 107 - 53 - or adsorbents, colourings, flavourings or sweeteners. For parenteral administration there are suitable especially infusion solutions, preferably isotonic aqueous solutions or suspensions, it being possible to prepare these before use, for example from lyophilised preparations that contain the active ingredient on its own or together with a carrier, for example mannitol. Such preparations may be sterilised and/or contain adjuncts, for example preservatives, stabilisers, wetting agents and/or emulsifiers, solubilisers, salts for regulating the osmotic pressure and/or buffers. The present pharmaceutical preparations, which, if desired, may contain other pharmacologically valuable substances, are manufactured in a manner known per se, for example by means of conventional mixing, dissolving or lyophilising processes, and contain from approximately 0.1% to 100%, especially from approximately 1% to approximately 50% or, in the case of lyophili-sates, up to 100%, active ingredient. Depending upon the type of infection and the condition of the infected organism, the daily dose (oral or parenteral) used for the treatment of a warmblooded animal (human or animal) weighing approximately 70 kg is from approximately 100 mg to approximately 1 g. The following Examples serve to illustrate the invention. Temperatures are given in degrees Centigrade. The following abbreviations are used in the Examples: TLC : thin-layer chromatograph IR : infra-red spectrum UV : ultraviolet spectrum THF : tetrahydrofuran - 54 - > J 0 7 Example 1 : (5R,6S)-2-(imidazol-1-yl)-6-(tert.- butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester 3 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxo-azetidin-J-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are stirred for 5 hours at reflux temperature and under an argon atmosphere in 500 ml of absolute toluene. After cooling, the solvent is distilled off and the residue is chromatographed over silica gel (eluant: toluene/ethyl acetate 4:1); TLC (silica gel/ethyl acetate): Rf * 0.4; IR (CH2CI2): 1790; 1715; 1590 cm"1. The starting material can be manufactured as follows: a) (3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-triphenylmethylthioazetidin-2-one 12.5 g of triphenylmethylmercaptan are suspended in 70 ml of methanol at 0° and, over a period of 10 minutes, a total of 2.2 g of a 55% sodium hydride suspension in oil is added in portions thereto. An emulsion of 11.1 g of (3S,4R)-3-(tert.-butyldimethylsilyloxymethyl ) -4-methylsulphonylazetidin-2-one (European Patent Application No. 82113) in 70 ml of acetone and 70 ml of water is then added dropwise over a period of 30 minutes. After stirring for 30 minutes at 0° and for one hour at room temperature, the reaction mixture is concentrated in a rotary evaporator, methylene chloride is added thereto and the aqueous phase is separated off. The organic solution is washed with brine and dried over sodium sulphate. After concentration, the crude title compound is purified by chromatography over silica gel (eluant: toluene/ethyl acetate 19:1). TLC (toluene/ethyl acetate 19:1): Rj = 0.64; IR (methylene chloride): 2 107 - 55 - 3390; 1761; 1118; 835 cm"1 b) 2- [ (3S,4R)-3- (tert.-butyldimethylsilyloxymethyl)-4-triphenylmethylthio-2-oxoazetidin-1-yl]-2-hydroxyacetic acid allyl ester 27 g of molecular sieve (4&; are added to 8.4 g of (3S,4R) -3- (tert.-butyldimethylsilyloxymethyl) -4-tri-phenylmethylthioazetidin-2-one and 8.23 g of glyoxylic acid allyl ester ethyl hemiacetal in 170 ml of absolute toluene and the whole is stirred at 55° for 10 hours. After filtration and concentration in a rotary evaporator under reduced pressure, the crude product is purified by chromatography over silica gel (eluant; toluene/ethyl acetate 95:5); TLC (silica gel, toluene/-ethyl acetate 10:1): Rj = 0.37 and 0.27; IR (CH2C12): 3520, 1760, 1745 cm-1. c) 2-[ (3S,4R)-3- (tert.-butyldimethylsilyloxymethyl)-4-triphenylmethylthio-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester While stirring at -15°, 80 ul of thionyl chloride and 88 ul of pyridine are added in succession in the course of 5 minutes to a solution of 604 mg of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-triphenylmethylthio-2-oxoazetidin-1 -yl]-2-hydroxyacetic acid allyl ester in 5 ml of tetrahydrofuran. The white suspension is stirred for a further 1 hour at -10° and filtered over Hyflo. After washing the residue with toluene, concentration is carried out in a rotary evaporator. The residue is dissolved in 3 ml of dioxan; 293 mg of triphenylphosphine and 0.13 ml of lutidine are added and the whole is stirred for 2 hours at a bath temperature of 115°. The mixture is filtered over Hyflo and the resulting residue is then 2 1 0723 - 56 - washed with toluene. The combined filtrates are concentrated by evaporation. Chromatography of the residue over silica gel yields the pure product (eluant: toluene/ethyl acetate 95:5); TLC (silica gel, toluene/ethyl acetate 1:1): Rj = 0.18; IR (CH2C12): 1745; 1605 cm"1. d) The silver salt of 2- [ (3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-mercapto-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester 70 ml of a 0.5M aqueous silver nitrate solution are added at room temperature to 7.5 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-triphenylmethyl-thio-2-oxoazetidin-1-yl]-2-triphenylphosphoranylidene-acetic acid allyl ester in 87 ml of ether. A mixture of 3.6 ml of tributylamine, 0.18 ml of trifluoroacetic acid and 25 ml of ether is then added dropwise and the reaction mixture is stirred for a further 20 minutes. The solid material is then filtered off with suction and washed with ether, water and ether. For the purpose of purification, the solid material is made into a slurry in 40 ml of ether and 40 ml of water, filtered with suction and dried. IR (CH2C12): 1760; 1620 cm"1. e) 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester 4.27 g of the silver salt of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-mercapto-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid 2-allyl ester are dissolved in 40 ml of absolute methylene chloride and then added to a solution, cooled to 0°, - 57 - 2 10723 of 2.14 g of 1,1'-thiocarbonyldiimidazole in 40 ml of absolute methylene chloride. The suspension is stirred for 2.5 hours at 0° and is then filtered over Hyflo. The yellow solution is concentrated under a water-jet vacuum and the resulting residue is purified by column chromatography over silica gel (eluant: toluene/ethyl acetate 95:5 to 80:20). TLC (silica gel, toluene/ethyl acetate): Rf= 0.45; IR (CH2C12): 1760; 1620; 1105 cm-1. Example 2: (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester A solution of 105 mg of (5R,6S)-2-(imidazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester in 2.7 ml of absolute THP is cooled to -70° and there are added thereto, in succession, 0.11 ml of acetic acid and, dropwise over the course of 10 minutes, 5.9 ml of a 0.1M tetrabutyl-ammonium fluoride solution in THF. The cooling bath is removed and the reaction mixture is brought slowly to room temperature. After 2.25 hours at room temperature, the reaction mixture is concentrated in a rotary evaporator and taken up in ethyl acetate and aqueous NaHCC^ solution. The organic phase is separated off, washed with brine, dried over Na2SO^ and concentrated. The crude product is purified by chromatography over silica gel (eluant: toluene/ethyl acetate 3:1 to 1:3); TLC (silica gel, ethyl acetate): R, = 0.14; IR (CH-C1-): 3600; 1790; 1715; 1590 cm-1. Example 3: The sodium salt of (5R,6S)-2-(imidazol- 1 -yl)-6-hydroxymethyl-2-penem-3-carboxylic acid 0.38 g of (5R,6S)-2-(imidazol-1-yl)-6-hydroxy- / ■ /-r' • 210723 - - 58 - methyl-2-penem-3-carboxylic acid allyl ester are dissolved in 16 ml of absolute THF and cooled to -10°, and 40 mg of tetrakis-(triphenylphosphine)-palladium and 0.4 ml of tributyltin hydride are added thereto. After stirring for 20 minutes at -10°, 86 ul of acetic acid are added and the reaction mixture is stirred for a further 10 minutes at -10°. After concentration in a rotary evaporator, the residue is taken up in water/ethyl acetate, cooled, and rendered basic with NaHCOj. The aqueous phase is separated off, washed twice with ethyl acetate and, after concentration in a rotary evaporator, purified over an XAD-2 column (eluant: water). The combined fractions are lyophilised. TLC (Reverse Phase Opti UCP]2» I^O/acetonitrile): Rf = 0.57; UV (water): Xmax = 310 *"»• Example 4: (5R,6S)-2-(pyrazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl )-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 84 mg of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(pyrazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester are reacted to form the title compound. IR (methylene chloride): 1785; 1705; 1580 cm-1. The starting material can be manufactured as follows: Analogously to Example le), 0.21 g of the silver salt of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-mercapto-2-oxoazetidin-1-yl]-2-triphenyl-phosphoranylideneacetic acid allyl ester is reacted to form the title compound by reaction with 1,1'-thio-carbonyldipyrazole. IR (methylene chloride): 1750; 1615 cm-1. - 59 - 2 107 Example 5: (5R,6S)-2-(pyrazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 50 mg of (5R,6S)-2-(pyrazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester are converted into the title compound. IR (methylene chloride): 3600; 1785; 1710; 1580 cm-1. Example 6: The sodium salt of (5R,6S)-2-(pyrazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 130 mg of (5R,6S)-2-(pyrazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester are reacted to form the title compound. UV (water): Xmax = 312 nm. Example 7: (5R,6S)-2-(1,2,4-triazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 102 mg of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(1,2,4-triazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-l-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are reacted to form the title compound. IR (methylene chloride): 1795; 1710; 1585 cm"'. The starting material can be manufactured as follows: Analogously to Example 1e), 0.21 g of the silver salt of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-mercapto-2-oxoazetidin-1-yl]-2-triphenyl-phosphoranylideneacetic acid 2-allyl ester is reacted to form the title compound by reaction with 1,1'-thiocarbonyldi-(1,2,4-triazole). IR (methylene chloride): 1755; 1620 cm-1 - 60 - 723 Example 8; (5R,6S)-2- (1,2,4-triazol-1-yl)-6-hydroxy-methyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 850 mg of (5R,6S)-2-(1 f2,4-triazol-1-yl)-6-(tert.-butyld imethylsilyloxy-methyl)-2-penem-3-carboxylic acid allyl ester are converted into the title compound. IR (methylene chloride): 3610; 1790; 1710; 1585 cm-t . Example 9: The sodium salt of (5R,6S)-2-(1,2,4- triazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 510 mg of (5R,6S)-2-(1,2,4-triazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl) -2-penem-3-carboxylic acid allyl ester are reacted to form the title compound. UV (water): Xmax = 310 nm- Example 10: (5R,6S)-2-(imidazol-1-yl)-6-[(1*R)-1- (tert.-butyldimethylsilyloxyethyl)]-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 0.76 g of 2-[(3S,4R)-3-[(1 * R)—1-tert.-butyldimethylsilyloxyethyl]-4-(imidazol-1 -ylthiocarbonylthio)-2-oxazetidin-1 -yl]-2-triphenyl-phosphoranylideneacetic acid allyl ester is reacted to form the title compound. TLC (silica gel; ethyl acetate): Rf = 0.74; IR (CH2C12): 1790; 1715; 1587 cm"1. The starting material can be manufactured as follows: a) N-p-methoxybenzyl-N-tert.-butylthiomethylammonium chloride At room temperature, a solution of 2.88 g (78.8 mmol) of hydrogen chloride in 20 ml of aceto- 210723 - 61 - nitrile arid 6.45 g (71.66 mmol) of tert. -butylmercaptan are added in succession to a solution of 10.69 g (23.9 mmol) of 1,3,5-tris-(£-methoxybenzyl)-hexa-hydro-1,3,5-triazine, which can be manufactured according to the method described in Chemical Abstracts 80, 37128a (1974), in 170 ml of acetonitrile. The mixture is stirred for 22 hours. Undissolved material is filtered off with suction and the filtrate is concentrated under reduced pressure. A crystalline residue is obtained which is stirred with ether and filtered with suction. Melting point 142°. b) (2S,3R)-N-p-methoxybenzyl-N-tert.-butylthiomethyl-2-bromo-3-hydroxybutyramide At room temperature, 2.76 g (10 mmol) of N-£-methoxybenzyl-N-tert.-butylthiomethylammonium chloride, 2.06 g (10 mmol) of dicyclohexyl carbodiimide and, i dropwise, 1.40 ml (10 mmol) of triethylamine are added ; in succession to a solution of 1.83 g (10 mmol) of | (2S,3R)-2-bromo-3-hydroxybutyric acid, manufactured J analogously to the method described by Shimohigashi Y. j et al., Bull. Chem. Soc. Japan 52, 949 (1979). The i resulting reaction mixture is stirred for two hours at , i room temperature. The dicyclohexylurea that has separated out is filtered off with suction and the filtrate is diluted with methylene chloride and washed with water and phosphate buffer solution having a pH of 8. The organic phase is dried over sodium sulphate and concentrated by evaporation and the oily residue is chromatographed over silica gel using toluene/ethyl acetate. The title compound is obtained in the form of a colourless, viscous oil. Rf (toluene/ethyl acetate 1:1): 0.55; IR (in methylene chloride): 3550-3200; 2950-2850; 1632; 1608; 1508; 1457; 1438; 1407; 1360; 1242; 1202; 1175; 1150; 1 028 cm"1. _ \ fc N N -\\ -3SEPW®£ - 62 - 2 10723 ~ c) (2S,3R)-N-p-methoxybenzyl-N-tert.-butylsulphonyl-me thy l-2-bromo-3-hydroxybutyrami.de At -14°, while stirring, 2.06 g (approximately 2.2 equivalents) of 90% m-chloroperbenzoic acid are added to a solution of 1.97 g (4.89 mmol) of (2S,3R)-N-£-methoxybenzyl-N-tert.-butylthiomethyl-2-bromo-3-hydroxybutyramide in 50 ml of methylene chloride. The reaction mixture is stirred at 0° for 80 minutes. The m-chlorobenzoic acid that has separated out is filtered off, the filtrate is diluted with methylene chloride and shaken in succession with 3% aqueous sodium bisulphite solution and 8% aqueous sodium bicarbonate solution. The organic phase is dried over sodium sulphate and concentrated by evaporation under reduced pressure and the residue is chromatographed over silica gel using toluene/ethyl acetate (7:1) and (6:1). The title compound is obtained in the form of a colourless, viscous oil. Rj (toluene/ethyl acetate 1:1): 0.43; [a] = +88 +_ 1° (1.01% in chloroform). The 1H-NMR spectrum (400 MHz in cdci3) points to the existence of two rotamers in a ratio of 1.3:1. d) N-p-methoxybenzyl-N-tert.-butylsulphonylmethyl-(2R,3R)-2,3-epoxybutyramide At -14° and with the exclusion of moisture, 340 ml of 1,5-diazabicyclo[5.4.0]undec-5-ene in 1 ml of tetrahydrofuran are added to a solution of 486 mg (1.1 mmol) of (2S,3R)-N-£-methoxybenzyl-N-tert.-butylsulphonylmethyl-2-bromo-3-hydroxybutyramide in 8 ml of tetrahydrofuran. The solution is stirred at room temperature for 75 minutes. After the addition of methylene chloride, the organic phase is extracted by shaking with 15% aqueous citric acid solution and 8% aqueous sodium bicarbonate solution. The organic phase is dried over sodium sulphate and concentrated by r i i i * '•A 2 107 23 * • evaporation Under reduced pressure. After chromatography of the residue over silica gel using toluene/ethyl acetate (4:1) the title compound is obtained in the form of a colourless, viscous oil. Rj (toluene/ethyl acetate 1:1): 0.29; [n] =45+1° (1.065% in chci3). The 1H-NMR spectrum (400 MHz in cdci3) points to the existence of two rotamers in a ratio of 1:2.8. e) (3S,4R)-1-p-methoxybenzyl-3-[(1'R)-1-hydroxy-ethyl]-4-tert.-butylsulphonyl-2-azetidinone While stirring at 0° and with the exclusion of moisture, 7 ml of a solution of dehydrated tetra-n-butylarnmonium fluoride in THF, manufactured by dehydrating 5 g of tetra-n-butylammonium fluoride trihydrate at 55° and under 0.1 torr and making up to 20 ml with tetrahydrofuran, are added dropwise to a solution of 398 mg (1.12 mmol) of N-£-methoxybenzyl-N-tert.-butylsulphonylmethyl-(2R,3R)-2,3-epoxybutyramide in 2.5 ml of tetrahydrofuran. Activated molecular sieve of 4? is added to the reaction mixture and the whole is stirred for two hours. The molecular sieve is filtered off with suction and washed four times with 20 ml of methylene chloride each time. 5 parts of diethyl ether are added to each individual filtrate and the filtrates are washed in succession with an aqueous phosphate buffer solution having a pH of 8. The combined organic phases are dried over magnesium sulphate and concentrated by evaporation under reduced pressure. The residue is chromatographed over 20 g of silica gel using toluene/ethyl acetate (3:1) and the crystalline title compound is obtained. Melting point 112°-113° (Kofler, from methylene chloride, diethyl ether, pentane); Rf (toluene/ethyl acetate 1:1): 0.27; [a] = +9 + 10 (1.105% in chloroform); 1H-NMR i -/ A - 64 - u 723 spectrum (400 MHz in cdci3): £ * 4.65 for proton (a) at the 4(R)-carbon atom, ■ 3.61 for proton (b) at the 3(S)-carbon atom and of = 4.09 for proton (c) at the 1'(R)-carbon atom of the hydroxyethyl group; J a-b: approx. 2, J b-c: approx. 7. f) (3S,4R)-3-[(1'R)-1-hydroxyethyl)-4-tert.butyl- sulphonyl-2-azetidinone A solution of 71 mg (0.2 mmol) of (3S,4R)-1-£-methoxybenzyl-3-[(11R) — 1-hydroxyethyl]-4-tert.-butyl-sulphonyl-2-azetidinone in 4 ml of acetonitrile is added to a well stirred solution, which has been heated to 65°, of 428 mg (1.8 mmol) of sodium peroxo-disulphate, 174 mg (1 mmol) of dipotassium biphosphate, 1 mg of iron (II) sulphate heptahydrate and 2 mg of copper(II) acetate hydrate in 4 ml of water. The reaction mixture is stirred for two hours at 65°. The organic solvent is distilled off under reduced pressure and the aqueous residue is extractd with ethyl acetate. After concentration of the organic phase in vacuo, the residue is crystallised from methylene chloride/diethyl ether and the title compound is obtained. Melting point 194°; R^ (ethyl acetate): [a] = +13 + 1° (0.75% in methanol); 'h-NMR spectrum (400 MHz in CD3OD): £ = 5.04 for proton (a) at the 4(R)-carbon atom, S = 3.58 for proton (b) at the 3(S)-carbon atom and = 4.19 for proton (c) at the 1'(R)-carbon atom of the hydroxyethyl group; J a-b: approx. 2, J b-c: approx. 4.5. g) (3S,4R) -3-[(1'R)-1 -(tert.-butyldimethylsilyloxy-ethyl)]-4-tert.-butylsulphony1-2-azetidinone 135 mg (0.574 mmol) of (3S,4R)-3-[(1'R)-1"hydroxyethyl ] -4-tert . -butylsulphonyl-2-azetidinone are stirred at room temperature for two hours with 173 mg / ; /V 2 10723 - 65 - (1.15 mmol) of tert.-butyldimethylchlorosilane and 78 mg (1.15 mmol) of imidazole in 3 ml of dimethyl-formamide. The reaction mixture is concentrated by evaporation ijT_ vacuo. The residue is taken up in ethyl acetate and washed with 8% aqueous sodium k bicarbonate solution. After drying of the organic phase over sodium sulphate and concentration by evaporation under reduced pressure, the title compound ./ \ is obtained in the form of a crystalline residue. By j-# ' chromatography over silica gel using toluene/ethyl acetate (4:1) the residue is freed of traces of j imidazole, and white crystals are obtained. Melting f point 196°; Rj (toluene/ethyl acetate 1:1): 0.48; j [a] - +11 + 1°. j > i i , ; h) (3S,4R)-3-[(1'R) -1 - (tert.-butyldimethylsilyloxy- ethyl) ] -4-triphenylmethylthioazetidin-2-one [ ■*"> Analogously to Example la), 6.99 g of (3S,4R)-3- j [ (1 ' R) -1 - (tert. -butyldimethylsilyloxyethyl) ] -4-tert. - j butylsulphonylazetidin-2-one are converted into the title compound. TLC (toluene/ethyl acetate 4:1): Rf = 0.57; IR (CH2C12) 3400; 1765 cm-1. i) 2-[(3S,4R)-3-[(1'R)-1-(tert.-butyldimethylsilyloxyethyl ) ] -4-triphenylmethylthio-2-oxoazetidin-1-yl]-2-hydroxyacetic acid allyl ester Analogously to Example 1b), 9.55 g of (3S,4R)-3- [ (1 'R)-1-(tert. -butyldimethylsilyloxyethyl) ] -4-tri-phenylmethylthioazetidin-2-one are converted into the title compound. TLC (toluene/ethyl acetate 19:1): ' Rf = 0.32 and 0.2; IR (CHjClj): 3520; 1765; 1750 cm"1. - 66 - 2107 j) 2-[(3S,4R)-3-[ (1 ' R) -1 - (tert.-butyldimethylsilvl-oxyethyl)]-4-triphenylmethylthio-2-oxoazetidin-1 —y1]-2-triphenylphosphoranylideneacetic acid allyl ester. Analogously to Example Ic), 12.5 g of 2-[(3S,4R)-3-[(1 * R)— 1 — (tert.-butyIdimethylsilyloxyethyl)] - 4-triphenylmethylthio-2-oxoazetidin-1-yl]-2-hydroxyacetic acid allyl ester are converted into the title compound. TLC (toluene/ethyl acetate 4:1): R^ * 0.38; IR (CH2C12): 1740; 1615 cm-1. k) The silver salt of 2-[(3S,4R)-3-[(1'R)-1 -(tert.-butyldimethylsilyloxyethyl)]-4-mercapto-2-oxoazetidin-1-yl]-2-triphenylphosphoranylidene-acetic acid allyl ester Analogously to Example Id), 8.47 g of 2-[(3S,4R)-3-[(1* R)— 1 —(tert.butyldimethylsilyloxyethyl)]-4-triphenylmethyl thio-2-oxoazet id in-1 -yl] -2-triphenylphos-phoranylideneacetic acid allyl ester are converted into the title compound. IR (CH2C12): 1760; 1615 cm-1. 1) 2-[(3S,4R)-3-[(1'R)-1 -(tert.butyldimethylsilyloxyethyl) ]-4-(imidazol-1-y1thiocarbonylthio)-2-oxoazetidin-1-yl]-2-triphenylphosphoranylidene-acetic acid allyl ester Analogously to Example 1e), 5.09 g of the silver salt of 2-[(3S,4R)-3-[(1"R)-1-(tert.-butyldimethylsilyloxyethyl) ]-4-mercapto-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are reacted with 2.5 g of thiocarbonyldiimidazole. After purification by means of column chromatography (eluant: toluene/ethyl acetate 1:1), the title compound is obtained. TLC (silica gel, ethyl acetate): Rf = 0.42; IR (CH2C12): 1755; 1620; 1110 cm"'. Example 11: (5R,6S)-2-(imidazol-1-yl)-6-[(1'R)-1 - hydroxyethyl]-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 0.33 g of (5R,6S)-2-(imidazol-1-yl)-6-[(I*R)-1-tert.-butyldimethylsilyloxyethyl] -2-penem-3-carboxylic acid allyl ester is converted into the title compound. TLC (silica gel, ethyl acetate): Rf * 0.13? IR (CH2CI2): 3600; 1790; 1715; 1587 cm-1. Example 12: The sodium salt of (5R,6S)-2-(imidazol-1-yl)-6-[(1'R)-1-hydroxyethyl]-2-penem-3-carboxylic acid Analogously to Example 3, 132 mg of (5R,6S)-2-(imidazol-1-yl)-6-[(1'R)-1-hydroxyethyl]-2-penem-3-carboxylic acid allyl ester are converted into the title compound. TLC (Reverse Phase Opti UCPi2, water): Rf = 0.14; UV (phosphate buffer pH 7.4): Xmax = 309'5 nm* Example 13: (5R,6S)-2-(pyrrol-1-yl)-6-(tert.-butyl-dimethyls ilyloxymethyl) -2-penem-3-carboxylic acid allyl ester 5.4 g of (3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4- [(pyrrol-1-yl)-thiocarbonylthio]-azetidin-2-one are dissolved in 60 ml of absolute Cl^C^f and then 6 g of CaC03 and, at +10°, 2.7 g of allyl-oxalyl chloride are added in succession thereto. After the dropwise addition, over a period of 5 minutes, of 3.3 ml of Hunig base in 10 ml of methylene chloride, the mixture is stirred for a further 30 minutes at 1 0°. The reaction mixture is diluted with chloroform (absolute), washed twice with ice-water, dried over Na2SO^, filtered and concentrated to a volume of 2 10 7 2 3 68 25 ml. After dilution with 400 ml of absolute chloroform, the bath temperature is increased to 70° and a total of 6 ml of triethyl phosphite in 100 ml of chloroform are added to the mixture in the course of 2.5 hours. The reaction mixture is kept under a light reflux for 3.25 hours and then cooled and concentrated. The crude product is purified by chromatography over silica gel (eluant: toluene and toluene/ethyl acetate 97.5:2.5). TLC (silica gel, toluene/ethyl acetate 4:1): Rf = 0.67; IR (CH2C12): 1790; 1710;1575 cm-1. The starting material can be manufactured as follows : (3S,4R) -3-(tert.-butyldimethylsilyloxymethyl)-4-[(pyrrol-1-yl)-thiocarbonylthio]-azetidin-2-one 11.72 g of (3S,4R)-3-tert.-butyldimethylsilyloxymethyl )-4-methylsulphonylazetidin-2-one [European Patent Specification No. 82113; cf. Chemical Abstracts 99, 139637a (1983)] are dissolved in 150 ml of absolute ethanol, and a solution of 10.88 g of potassium N-pyrroledithiocarboxylate [for manufacture see R.D. Beremann, D. Nalewajek, Inorganic Chemistry 1 6, 2687 (1977)] in 150 ml of absolute ethanol is added dropwise thereto. After stirring for one hour at room temperature, the reaction mixture is concentrated in a rotary evaporator and the residue is partitioned between ethyl acetate and water. After washing of the organic phase with brine and drying of the same over sodium sulphate, the solvent is removed jji vacuo. The crude product is purified by chromatography over silica gel. TLC (silica gel; toluene/ethyl acetate 4:1): Rf - 0.5; IR (CH2C12): 3410; 1780; 1310; 1110 cm"1. Example 14: (5R,6S)-2-(pyrrol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 1.1 g of (5R,6S)-2- T £ o "3SEP1987 - 69 - 2 1 (pyrrol-1-yl)-6-tert.-butyldimethylsilyloxymethyl-2-penem-3-carboxylic acid allyl ester are converted into the title compound. TLC (ethyl acetate): Rf = 0.5; IR (CH2C12): 3600, 1785; 1705, 1575 cm"1. Example 15: The sodium salt of (5R,6S)-2-(pyrrol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 0.36 g of (5R,6S)-2-(pyrrol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester is converted into the title compound. UV (water): Xmax = 310 nm. Example 16: 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4- [ (pyrazol-1-yl)-thiocarbonyl-thio]-2-oxoazetidin-1-yl]-2-triphenyl-phosphoranylideneacetic acid allyl ester. 108 mg of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are dissolved in 0.6 ml of absolute dimethylformamide, and 51 mg of pyrazole are added thereto. After stirring for 6 hours at 40°, the reaction mixture is poured onto ice-water. The precipitate is filtered off and washed with water. The residue is taken up in ethyl acetate, washed with brine, dried over Na2S04, filtered and concentrated. The crude product is purified by chromatography over silica gel (eluant: toluene to toluene/ethyl acetate 85:15). IR (methylene chloride): 1750; 1615 cm~^; TLC (toluene/ethyl acetate 1:1): Rf = 0.55. The product is identical to that described in Example 4. ? * 4L a - 70 - Example 17: (5R,6S)-2-(4-methylpyrazol-l-yl)-6-(tert butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 1.15 g of 2-[(3S,4R)-3-(tert. -butyldimethylsilyloxymethyl)-4-[(4-methylpyrazol 1 -yl) - thiocarbonylthio]-2-oxoazetidin-l-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are converted into the title compound. IR (CH2C12): 1780; 1700; 1590; 1565 cm*1. The starting material can be manufactured as follows: 2- [ (3S,4R) -3- (tert.-butyldimethylsilyloxymethyl)-4-[ (4-methylpyrazol-l-yl)-thiocarbonylthio]-2-oxoazetidin-l -y 11 -2-triphenylphosphorany1ideneacetic acid allyl ester Analogously to Example 16, 1.43 g of 2-[(3S,4R)-3-(tert. -butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester in 10 ml of absolute DMF is reacted for 18.5 hours at room temperature with 0.49 ml of 4-methylpyrazole to form the title compound. TLC (toluene/ethyl acetate 1:1): Rf = 0.48; IR (CH2C12): 1750; 1615 cm"'. Example 18: (5R,6S)-2-(4-methylpyrazol-l-yl)-6- hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 0.44 g of (5R,6S)-2-(4-methylpyrazol-l -yl) -6- (tert. -butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester is converted into the title compound. IR (CH2C12): 3600; 1785; 1705; 1590; 1570 cm"1. ...i.-.-X.. I " •>- ' .. ■7 4 723 - - 71 - Example 19: The sodium salt of (5R,6S)-2-(4-methylpyrazol-l -yl )-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 0.19 g of (5R,6S)-2-(4-methylpyrazol-1-yl)-6-hydroxymethyl-2-penem-3-car-boxylic acid allyl ester is converted into the title compound. UV (water): Amax = 318 nm. Example 20: (5R,6S)-2- (4-methylimidazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 2.4 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(4-methyl-imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are converted into the title compound. IR (CH2CI2): 1790; 1710; 1585 cm*'. The starting material can be manufactured as follows: 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4- [(4-methylimidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-l -yl] -2-triphenylphosphoranylideneacetic acid / allyl ester Analogously to Example 3, 2.5 g of 2-[(3S,4R)- 3-tert.-butyldimethylsilyloxymethyl-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1 -yl]-2-triphenylphos-phoranylideneacetic acid allyl ester in 18 ml of absolute DMF are reacted for 1.5 hours at room temperature with 1.44 g of 4-methylimidazole to form the title compound. TLC (acetone/hexane 1:1): Rf = 0.5; IR (CH2C12): 1750; 1615 cm"1. r - 72 2 10723 Example 21: (5R,6S)-2-(4-methylimidazol-1-yl)-6- hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 0.75 g of (5R,6S)-2-(4-methy1imidazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl) -2-penem-3-carboxylic acid allyl ester is converted into the title compound. IR (CH2CI2): 3600; 1790; 1710; 1590 cm-1. Example 22: The sodium salt of (5R,6S)-2-(4-methyl-imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 0.36 g of (5R,6S)-2-(4-methylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester is converted into the title compound. UV (water): = 310 nm. Example 23: (5R,6S)-2-(3-ethylimidazolio)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester tetrafluoro-borate a) Process A: 2.0 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-(imidazol-1-ylthiocarbonylthio)-2-oxoaze-tidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are dissolved in 50 ml of absolute ethylene chloride, and, at 0°, 0.533 g of triethyloxonium tetrafluoroborate are added. The cooling bath is then removed and the whole is stirred for 21 hours at room temperature. After the addition of a further 50 mg of triethyloxonium tetrafluoroborate, the reaction mixture is stirred at 40° for 3 hours. The mixture is then washed twice with water and dried over sodium sulphate, filtered and concentrated. The residue is purified by 73 - 2 107 chromatography over silica gel (eluant: ethyl acetate to ethyl acetate/acetone 2:1). TLC (silica gel, ethyl acetate/acetone 4:1): Rf = 0.23; IR (methylene chloride): 1800; 1715; 1600 cm-'. b) Process B 21 mg of (5R,6S)-2-(imidazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl) -2-penem-3-carboxylic acid allyl ester are dissolved in 1 ml of absolute methylene chloride and cooled to -10°; 9.5 mg of triethyloxonium tetrafluoroborate are added and the whole is stirred for a further 1.75 hours at 0°. The reaction mixture is then diluted with methylene chloride, washed with water, dried and concentrated. The crude product is purified as in Process a). IR (methylene chloride): as above. Example 24: (5R,6S)-2-(3-ethylimidazolio)-6-[(1'R)-1-(tert.-butyldimethylsilyloxyethyl)]-2-penem-3-carboxylic acid allyl ester tetrafluoroborate Analogously to Example 23b), 0.6 g of (5R,6S)-2-(imidazol-1-yl)-6-[(1'R)-1-tert.-butyldimethylsilyloxyethyl ] -2-penem-3-carboxylic acid allyl ester is converted into the title compound. IR (methylene chloride): 1800; 1718; 1600 cm-'. Example 25: (5R,6S)-2-(3-ethylimidazolio)-6-hydroxy-methyl-2-penem-3-carboxylic acid allyl ester tetrafluoroborate Analogously to Example 2, 0.1 g of (5R,6S)-2-(3-ethylimidazolio)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester tetrafluoroborate is converted into the title compound. IR (methylene chloride): 3600; 1800; 1715; 1600 cm"1. - 74 - 2 1 0 7 2 ? *" Example 26: (5R,6S)-2-(3-ethvlimidazolio)-6-[(1'R)-1-hydroxyethyl]-2-penem-3-carboxylic acid allyl ester tetrafluoroborate Analogously to Example 2, 0.15 g of (5R,6S)-2-(3-ethylimidazolio)-6-[(1•R)—1 — (tert.butyldimethylsilyloxyethyl) ]-2-penem-3-carboxylic acid allyl ester tetra-fluoroborate is converted into the title compound. IR (methylene chloride): 3600; 1800; 1718; 1600 cm-1. Example 27: (5R,6S)-2- (3-ethylimidazolio)-6-hydroxy-methyl-2-penem-3-carboxylate Analogously to Example 3, 80 mg of (5R,6S)-2-(3-ethylimidazolio)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester tetrafluoroborate are converted into the title compound, which is purified by chromatography over Antec gel (OPTI UPC12). UV (phosphate buffer pH 7.4): Xmax =312 ym. Example 28: (5R,6S)-2-(3-ethylimidazolio)-6-[(1'R)— 1 — hydroxyethyl]-2-penem-3-carboxylate Analogously to Example 3, 237 mg of (5R,6S)-2-(3-ethylimidazolio)-6-[(1'R)-1-hydroxyethyl]-2-penem-3-carboxylic acid allyl ester tetrafluoroborate are converted into the title compound. UV (phosphate buffer pH 7.4): Amax =319 um. Example 29: (5R,6S)-2-(4,5-dimethy1imidazol-1-yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 0.15 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(4,5-dimethyl-imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester is converted into the title compound. IR (CH2CI2): / L—L 2 10723 „ 75 - 1790; 1715; 1590 cm*1. The starting material 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-[(4,5-dimethylimidazol-1-yl)-thiocarbonylthio]-2-oxoazet id in-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester can be manufactured as follows: Analogously to Example 16, 3 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazet id in-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester in 20 ml of DMF are reacted at room temperature for 6 hours with 2.1 g of 4,5-dimethylimidazole to form the title compound. TLC (toluene/ethyl acetate 1:1): Rf = 0.2; IR (CH2C12): 1750; 1615 cm-1. Example 30: (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 90 mg of (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-(tert.-butyldimethylsilyloxy-methyl)-2-penem-3-carboxylic acid allyl ester are converted into the title compound. IR (CH2C12): 3590; 1790; 1710; 1590 cm"1. Example 31: The sodium salt of (5R,6S)-2-(4,5- dimethylimidazol-1 -yl)-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 0.43 g of (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester is converted into the title compound. UV (water): Xmax =312 nm. - 76 - 2 107 Example 32; (5R,6S)-2-[4-allyloxycarbonylaminoethyl-imidazol-1-yl]-6-(tert.-butyldimethyl-silyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 2.85 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[4-allyloxycar-bonylaminoethylimidazol-1-ylthiocarbonylthio]-2-oxoaze-tidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are converted into the title compound. IR (CH2C12)s 3440; 1790; 1710; 1585 cm"1. The starting compound can be manufactured as follows: a) 3-allyloxycarbonyl-2-thiazolidinethione 16.7 g of 2-mercaptothiazoline are dissolved in 140 ml of methylene chloride and, at 0° and in the course of 20 minutes, 20.5 ml of triethylamine and 14.9 ml of chloroformic acid allyl ester in 35 ml of methylene chloride are added in succession thereto. After stirring for a further 75 minutes at room temperature, the reaction mixture is washed first with water and then with brine. After drying over sodium sulphate and concentration, the crude product is purified by chromatography over silica gel (eluant: toluene/ethyl acetate 95:5). TLC (silica gel; toluene/ethyl acetate 1:1): Rf = 0.53; IR (CH2C12): 1750; 1720 cm "1. b) 4-(2-allyloxycarbonylaminoethyl)-imidazole 60 ml of absolute THF are added to 5.55 g of 4-(2-aminoethyl)-imidazole (hydrochloride), and then a solution of 6 g of 3-allyloxycarbonyl-2-thiazolidine-thione in 60 ml of absolute THF is added dropwise thereto. After the addition of 8.4 ml of triethylamine, the mixture is stirred for 65 hours at room temperature. After diluting with 100 ml of methylene 2 10723 . 77 - chloride and filtering off the insoluble portion, concentration is carried out in a rotary evaporator. The residue is again taken up in methylene chloride, is filtered again and, after being concentrated, is purified by column chromatography. (Eluant: ethyl acetate to ethyl acetate/acetone 1:1); TLC (silica gel, ethyl acetate/acetone 2:1): Rf = 0.09. c) 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[4-(2-allyloxycarbonylaminoethyl)-iinidazol-1-ylthiocarbonylthio]-2-oxoazetidin-1-yl]-2-tri-phenylphosphoranylideneacetic acid allyl ester Analogously to Example 16, 3 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester in 25 ml of DMF are reacted with 3.3 g of 4-allyloxycarbonylaminoethyl-imidazole to form the title compound. IR (CH2CI2): 3440; 1750; 1720; 1615 cm"1. Example 33: (5R,6S)-2-[4-(2-allyloxycarbonylamino- ethyl)-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 1.13 g of (5R,6S)-2-[4-(2-allyloxycarbonylaminoethylimidazol-1-yl]-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester are converted into the title compound. IR (CH2C12): 3600; 3440; 1790; 1710; 1585 cm"1. Example 34: (5R,6S)-2-[4-(2-aminoethylimidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid. Analogously to Example 3, 0.51 g of (5R,6S)-2-[4-(2-allyloxycarbonylaminoethy1imidazo1-1-yl]-6-hydroxy-methyl-2-penem-3-carboxylic acid allyl ester is f 2 107 - 78 - converted into the title compound. UV (phosphate buffer pH 7.4): Xmax =310 nm. Example 35: (5R,6S)-2-(4-methoxyimidazol-1 -yl)-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester Analogously to Example 1, 1.85 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(4-methoxyimidazol-1 -yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester are converted into the title compound. IR (CH2CI2): 1790; 1710; 1585 cm-1. The starting material 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl) -4-[(4-methoxyimidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester can be manufactured as follows: Analogously to Example 16, 2.15 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphos-phoranylideneacetic acid allyl ester in 20 ml of DMF are converted using 1.18 g of 4-methoxyimidazole into the title compound. IR (CH2CI2): 1750; 1610 cm"1. Example 36: (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester Analogously to Example 2, 0.62 g of (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-(tert.-butyldimethylsilyloxymethyl) -2-penem-3-carboxylic acid allyl ester is converted into the title compound. IR (CH2Cl2): 3600; 1790; 1710; 1582 cm ~1. 210723- - 79 - Example 37; The sodium salt of (5R,6S)-2-[4-methoxy-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid Analogously to Example 3, 0.31 g of (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-hydroxymethy1-2-penem-3-carboxylic acid allyl ester is converted into the title compound. UV (water); Xmax ■ 310 nm. Example 38; (5R,6S)-2-[4-allyloxycarbonylaminomethyl-imidazol-1-yl]-6-(tert.-butyldimethylsilyloxymethyl) -2-penem-3-carboxylic acid allyl ester. Analogously to Example 2, 0.196 g of 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl)]-4-[4-allyloxycar-bonylaminomethylimidazol-1-yl)-thiocarbonylthio]-2-oxo-azetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester is converted into the title compound. IR (CH2C12): 3440; 1730; 1715; 1585 cm"1. The starting material 2-[(3S,4R)-3-(tert.-butyldimethylsilyloxymethyl )]-4-[4-allyloxycarbonylamino-methyl imidazol-1 -yl)-thiocarbonylthio]-2-oxoazetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester can be manufactured as follows: Analogously to Example 16, 0.286 g of 2-[(3S,4R)-3 -(tert.-butyldimethylsilyloxymethyl)-4-[(imidazol-1-yl)-th iocarbony1thio]-2-oxoazetidin-1-yl]-2-triphenyl-phosphoranylideneacetic acid allyl ester is converted using 0.29 g of 4-allyloxycarbonylaminomethylimidazole in 2 ml of DMF into the title compound. IR (CH2C12); 3450; 1755; 1715; 1615 cm-1. Example 39; (5R,6S)-2-[4-allyloxycarbonylaminomethyl-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid allyl ester. Analogously to Example 2, 9.15 g of (5R,6S)—2—[4— ( - 80 - 2 10723 ** allyloxycarbonylaminomethylimidazol-1-yl]-6-(tert.-butyldimethylsilyloxymethyl)-2-penem-3-carboxylic acid allyl ester are converted into the title compound. IR (CH2C12): 3600; 3440; 1790; 1715; 1590 cm"1. Example 40: (5R,6S)-2-[4-aminomethylimidazol-T-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid. Analogously to Example 3, 2 g of (5R,6S)— 2 — [4 — allyloxycarbonylaminomethylimidazol-1-yl]-6-hydroxy-methyl-2-penem-3-carboxylic acid allyl ester are converted into the title compound. UV (phosphate buffer, pH 7.4): Xmax =312 nm. Example 41: The following compounds can be manufactured in a manner analogous to that described in the preceding Examples: The sodium salt of (5R,6S)-2-(pyrazol-1-yl)-6-[ (1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 310 nm. The sodium salt of (5R,6S)-2-(1,2,4-triazol-1-yl)-6-[ (1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,6S)-2-(pyrrol-1-yl)-6-[(1R)-1 -hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax 3'0 nm. The sodium salt of (5R,6S)-2-(tetrazol-1-yl)-6-hydroxy-methyl-2-penem-3-carboxylic acid, UV (water): Xmax = 310 nm. The sodium salt of (5R,6S)-2-(tetrazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 31^ nm. The sodium salt of (5R,6S)-2-(5-aminotetrazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax ~ 31 * nn1, ; f i i i •V - , - 81 - 2 1 07 23 The sodium salt of (5R,6S)-2-(5-aminotetrazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,6S)-2-(indol-1-yl)-6-hydroxy-methyl-2-penem-3-carboxylic acid, UV (water): Xmax = 311 nm. The sodium salt of (5R,6S)-2- (indol-1-yl)-6-[(1R)-1 -hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 311 nm* The sodium salt of (5R,6S)-2-[IH-pyrrolo (2,3-b)pyrid-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 310 nm. The sodium salt of (5R,6S)-2-[IH-pyrrolo(2,3-b)pyrid-1-yl]-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,6S)-2-(benzimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = nm* The sodium salt of (5R,6S)-2-(benzimidazol-1-yl)-6-[(IR)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Amax = 311 nm. The sodium salt of (5R,6S)-2-(benzotriazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 31^ nm* The sodium salt of (5R,6S)-2-(benzotriazol-1-yl)-6-[(IR)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Amax =313 nm. The sodium salt of (5R,6S)-2-[IH-imidazo(4,5-b)pyrid-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,6S)-2-[IH-imidazo(4,5-b)pyrid-1-yl]-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 312 nm. The sodium salt of (5R,6S)-2-(purin-1-yl)-6-hydroxy-methyl-2-penem-3-carboxylic acid, UV (water): Xmax = • ' 2107 2 3 - 82 - 314 nm. The sodium salt of (5R,6S)-2-(purin-1-yl)-6-[(1R)-1 - ^ hydroxyethyl)-2-penem-3-carboxylic acid, UV (water): X 313 nm. max x Example 42: The following 2-(imidazol-1-yl)-penem compounds can be manufactured in a manner analogous to that described in the preceding Examples: (5R,6S)-2-(2-aminoimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): X^^ = 309 nm. (5R,6S)-2-(2-aminoimidazol-1-yl)-6-[(1R)-1-hydroxyethyl] -2-penem-3-carboxylic acid, UV (water): ^max = 311 nm. (5R,6S)-2-(2-aminomethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 313 nm. (5R,6S)-2-(2-aminomethylimidazol-1-yl)-6-[(1R) — 1 — hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax ~ 31 ^ nnu The sodium salt of (5R,6S)-2-(2-nitroimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax "310 nm. The sodium salt of (5R,6S)-2- (2-nitroimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 311 nm. (5R,6S)-2-[4-(2-aminoethyl)-imidazol-1-yl]—6—[(IR)—1— hydroxyethyl]-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax =312 nm. (5Rf 6S)-2-(4-aminomethylimidazol-1-yl)-6-f(IR) — 1 — hydroxyethyl]-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Amax =312 nm. The sodium salt of (5R,6S)-2-(4-ethylimidazol-1-yl)-6- - 83 - 210 hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 31® nm• The sodium salt of (5R,6S)-2-(4-ethylimidazol-1-yl)-6-[(1R)-1-hydroxymethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4-propylimidazol-I-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = nm' The sodium salt of (5R,6S)-2-(4-propylimidazol-l-yl)-6-[(IR)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax ■ 311 nm. The sodium salt of (5R,6S)-2-(4-methoxyimidazol-1-yl)-6-[(1R)—1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax ■ 310 nm. The sodium salt of (5R,6S)-2-[4-(2-acetylaminoethyl)-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 309 nm. The sodium salt of (5R,6S)-2-[4-(2-acetylaminoethyl)-imidazol-1-yl]-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 310 nm. (5R,6S)-2-[4-(2-amino-2-methoxycarbonylethyl)-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 308 nm. (5R,6S)— 2—[4—(2-amino-2-methoxycarbonylethyl)-imidazol-1-yl]-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 310 nm. The sodium salt of (5R,6S)-2-(4-methylimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,6S)-2-(4-hydroxymethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xj,,^ =312 nm. The sodium salt of (5R,6S) -2-(4-hydroxymethylimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic / / ' * 2107 - 84 - acid, UV (water): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4-acetoxymethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Amax = 310 nm. The sodium salt of (5R,6S)-2-(4-acetoxymethylimidazol-1-yl)-6-[(IR)-1-hydroxyethyl)-2-penem-3-carboxylie acid, UV (water): Amax = 309 nm. The sodium salt of (5R,6S)-2-(4-methoxycarbonylmethyl-imidazol-l -yl) -6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4-methoxycarbonylmethyl-imidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-car-boxylic acid, UV (water): \max =310 nm. The sodium salt of (5R,6S)-2-(4-carbamoylmethylimid-azol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4-carbamoylmethy1imidazol-1 -yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylie acid, UV (phosphate buffer pH 7.4): Xmax = 311 nm. The sodium salt of (5R,6S)-2-(4-chloromethylimidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (phosphate buffer pH 7.4): Xmax =312 nm. The sodium salt of (5R,6S)-2-(4-chloromethylimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 310 nm. The disodium salt of (5R,6S)-2-(4-carboxymethylimid-azol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax = 309 nm. The disodium salt of (5R,6S)-2-(4-carboxymethylimid-azol-1-yl)-6-[(IR)-1-hydroxyethyl]-2-penem-3-carboxy-lic acid, UV (water): Amax = 309 nm. The sodium salt of (5R,6S)-2-(4-carbamoyloxymethylimid-azol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, UV (water): Xmax =313 nm. The sodium salt of (5R,6S)-2-(4-carbamoyloxymethylimid- - 85 - 2 10723 azol-l-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax =312 nm. The sodium salt of (5R,5S)-2-(4-methylthiomethylimidazol-1 -yl )-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid , UV (water): Xmax = 310 nm. The sodium salt of (5R,6S)-2-(4-ethylthiomethylimid-azol-1-yl)-6-[(1R)-f-hydroxyethyl]-2-penem-3-carboxylic acid, UV (water): Xmax = 309 nm. Example 43: (5R,6S)-2-(imidazol-1-yl)-6-[(1R) — 1 — hydroxyethyl]-2-penem-3-carboxylic acid acetoxymethyl ester 60.7 g of the sodium salt of (5R,6S)-2-(imidazol-1-yl)-6- [ (1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid are dissolved in 2 ml of absolute DMF and 0.2 ml of absolute DMSO and at 0°, while stirring, a solution of 39.8 mg of acetoxybromomethane in 0.3 ml of absolute DMF is added dropwise thereto. After stirring for 30 minutes at 0° and then for 30 minutes at room temperature, the reaction mixture is diluted with ethyl acetate and washed twice with brine. The organic phase is dried over magnesium sulphate and concentrated by evaporation. Purification by column chromatography (eluant: ethyl acetate) yields the title compound. TLC (silica gel, acetone): Rf = 0.7; IR (methylene chloride): 3590; 1790; 1765; 1725; 1580 cm-1; UV (ethanol): Xmax = 328.5 nm. Example 44: (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid 1-ethoxycarbonyl-oxyethyl ester 1.2 g of sodium iodide are dissolved in 3.7 ml of acetone, and 0.275 ml of ethyl-1-chloroethyl carbonate is added thereto. The mixture is stirred for 3 hours at room temperature. The solution is then added - 86 - 2 107 23 dropwise to 15 ml of methylene chloride and the inorganic salts which precipitate are filtered off. The methylene chloride solution is concentrated to 2 ml and, at 0°, added to a solution of 0.267 g (1 mmol) of (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid in 4 ml of dimethylacetamide. The whole is stirred for 3 hours at 0° and then diluted with ethyl acetate and washed three times with water. The organic phases are dried over sodium sulphate and concentrated in a rotary evaporator. The crude product is purified over 10 g of silica gel using the eluant ethyl acetate. The title compound is obtained in the form of a white foam. IR spectrum (methylene chloride): 3600; 1790; 1750; 1720; 1670 cm"1. Example 45: (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid pivaloyl-oxymethyl ester 0.6 g of sodium iodide is dissolved in 2 ml of acetone, and 0.15 ml of pivalic acid chloromethyl ester is added thereto. The mixture is stirred for 3 hours at room temperature and then added dropwise to 7.5 ml of methylene chloride. The inorganic salts which precipitate are filtered off. The methylene chloride solution is concentrated to 1 ml and, at 0°, added to a solution of 0.11 g (0.4 mmol) of (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid and 0.17 ml of diisopropylethylamine in 4 ml of N,N-dimethylacetamide. The whole is then stirred for 3 hours at 0° and then diluted with ethyl acetate and washed three times with water. The organic phase is dried over sodium sulphate and concentrated in a rotary evaporator. The crude product is purified over 10 g of silica gel using the eluant ethyl acetate. The title 2 107 2 % - 87 - compound is obtained in the form of a white foam. IR spectrum (methylene chloride): 3600; 1795; 1745; 1725; 1670 cm"1. Example 46: The following esters can be manufactured in a manner analogous to that described in Examples 43 to 45: (5R,6S)-2- (imidazol-1-yl)-6-hydroxymethyl-2-penem-3- carboxylic acid acetoxymethyl ester, IR (methylene chloride): 3620; 1795; 1765; 1725; 1670cm"1. (5R,6S)-2-(pyrazol-1-yl)-6-hydroxymethyl-2-penem-3- carboxylic acid acetoxymethyl ester, IR (methylene chloride): 3605; 1795; 1760; 1720 cm"1. (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-hydroxymethyl-2- penem-3-carboxylic acid acetoxymethyl ester, IR (methylene chloride): 3625; 1790; 1755; 1 730; 1680 cm"1. (5R,6S)-2-[4-aminomethylimidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid acetoxymethyl ester, IR (methylene chloride): 1785; 1760; 1725; 1685 cm"1. (5R,6S)-2-[4-aminomethylimidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid 1-ethoxycarbonyloxyethyl ester, IR (methylene chloride): 1790; 1755; 1720; 1675 cm"1. (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6 - [ (J R) —1 — hydroxyethyl]-2-penem-3-carboxylic acid acetoxymethyl ester, IR (methylene chloride): 3615; 1795; 1760; 1720; 1675 cm'1. (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6 - [ (1R)—I — hydroxyethyl]-2-penem-3-carboxylic acid 1-ethoxy-carbonyloxyethyl ester, IR (methylene chloride): 3610; 1785; 1755; 1715; 1665cm"1. (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-hydroxymethyl- - 88 - 2 107 2-penem-3-carboxylic acid acetoxymethyl ester, IR (methylene chloride): 3605; 1790; 1755; 1725; 1685 cm-1. (5R,6S)-2-(4-aminomethylimidazol-1-yl)-6 - [ (IR)-1 -hydroxyethyl]-2-pemem-3-carboxylic acid acetoxymethyl ester, IR (methylene chloride): 1785; 1760; 1720; 1 630 cm-'. (5R,6S)-2-(4-aminomethylimiazol-1-yl)-6-[ <1R)—1 — hydroxyethyl)-2-penem-3-carboxylic acid 1-ethoxy-carbonylethyl ester, IR (methylene chloride): 1785; 1755; 1720; 1670 cm-1. (5R,6S)-2-(imidazol-1-yl)-6-[(1R)-1-hydroxyethyl] -2-penem-3-carboxylic acid 1-ethoxycarbonyloxyethyl ester, IR (methylene chloride): 3600; 1790; 1760; 1720; 1675 cm*'. Example 47: Dry-filled ampoules or phials containing 0.5 g of the sodium salt of (5R,6S)-2-(imidazol-1-yl)-6-[(1'R)-1-hydroxyethyl]-2-penem-3-carboxylic acid as active substance are manufactured as follows: Composition (for 1 ampoule or phial): active substance 0.5 g mannitol 0.05 g A sterile aqueous solution of the active substance and the mannitol is subjected to freeze-drying under aseptic conditions in 5 ml ampoules or 5 ml phials and the ampoules or phials are sealed and tested. Instead of the above-mentioned active ingredient, it is also possible to use the same amount of a different active ingredient from the preceding Examples, such as, for example, the sodium salt of (5R,6S)-2-(pyrazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid, the sodium salt of (5R,6S)-2-(1,2,4- </div>

Claims

<div class="application article clearfix printTableText" id="claims"> - 89 - 2 1 07 triazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylie acid, (5R,6S)-2-(4-aminomethylimidazol-1-yl)-6-[(1R) — 1 — hydroxyethyl]-2-penem-3-carboxylic acid, the sodium salt of (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-[(1R)-1-hydroxyethyl]-2-penem-3-carboxylic acid or the sodium salt of (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid. 210723 90 WHAT WE CLAIM IS: 1. 2-heterocyclyl-6-hydroxy-lower alkyl-2-penem compounds of the formula R S —R 2 en O R 3 in which Rj represents lower alkyl substituted by hydroxy or by protected hydroxy, R2 represents an unsaturated azaheterocyclyl radical bonded via a ring nitrogen atom to the penem radical, and R3 represents carboxy or functionally modified carboxy, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of such compounds of the formula I having a salt-forming group. 2. Compounds of the formula I according to claim 1 in which R^ represents lower alkyl substituted by hydroxy or by protected hydroxy, R2 represents an optionally partially saturated monocyclic 5-membered heteroaryl radical that has from 1 to 4 ring nitrogen atoms and is bonded via a ring nitrogen atom to the penem radical, a corresponding partially saturated monocyclic 6-membered heteroaryl radical having from 1 to 3 ring nitrogen atoms, or a corresponding optionally partially saturated benzo, dibenzo, pyrido or pyrimido derivative of such a 5- or 6-membered radical, these radicals being unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lcwer V si r 3 SEP 1987 210? - 91 - alkylthio, phenylthio, lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, halo-lower alkyl, lower alkylthio-lower alkyl, optionally N-lower alkylated amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, sulpho-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, lower alkanoylamino, carboxy, lower alkoxycarbonyl, carbamoyl, N-mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho, sulphamoyl, phenyl optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, or cycloalkyl, nitro, imino, oxo and/or by oxido, R3 represents carboxy, esterified carboxy that can be cleaved under physiological conditions or protected carboxy R3', optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of compounds of the formula I having a salt-forming group. 3. Compounds of the formula I according to claim 1 in which Rj and R3 have the meanings given in claim 2 and R2 is one of the radicals indicated in claim 2, which radical is unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lower alkylthio, phenylthio, lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, optionally N-lower alkylated amino-lower alkyl, sulpho-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, lower alkanoylamino, carboxy, lower alkoxycarbonyl, carbamoyl, N- 210723 - 92 - mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho, sulphamoyl, phenyl optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, or cycloalkyl, nitro, imino, oxo and/or by oxido, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of compounds of the formula I having a salt-forming group. 4. Compounds of the formula I according to claim 2 in which Rj represents lower alkyl substituted by hydroxy or by tri-lower alkylsilyloxy, R2 represents 1-pyrrolyl or dihydro-1-pyrrolyl optionally substituted by lower alkyl or by halogen, imidazol-1-yl optionally substituted by lower alkyl, lower alkoxy, amino-lower alkyl, N-lower alkylated amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, halo-lower alkyl, sulpho-lower alkyl, lower alkylthio-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkanoylamino or by nitro, pyrazol-1-yl optionally substituted by lower alkyl, amino-lower alkyl, amino-carboxy-lower alkyl, amino or by nitro, 1,2,3-, 1,2,4- or 1,3,4-triazol-1-yl optionally substituted by lower alkyl, carboxy-lower alkyl or by phenyl, 1- or 2-tetrazolyl optionally substituted by lower alkyl, carboxy-lower alkyl, sulpho-lower alkyl, di-lower alkylamino-lower alkyl, amino or by optionally halo-substituted phenyl, dihydro-1-pyridyl that is unsubstituted or substituted by oxo and optionally additionally substituted by halogen, dihydro- or tetrahydro-1-pyrimidyl that is unsubstituted or substituted by oxo and optionally additionally 210 - 93 - substituted by lower alkyl, amino, di-lower alkylamino and/or by carboxy, dihydro- or tetrahydro-1,2,4- or -1,3,6-triazin-1-yl, each of which is optionally substituted by lower alkyl, lower alkoxy, amino and/or by up to 2 oxo groups, indol-1-yl, benzimidazol-1-yl, benzotriazol-I-yl, pyridopyrrol-1-yl, pyridoimidazol-1 -yl, or pyrimido-, dihydropyrimido- or tetrahydro-pyrimido-imidazol-1-yl each optionally substituted by amino, imino and/or by oxo, or pyrimido-, dihydro-pyrimido- or tetrahydropyrimido-1,2,3-triazol-1-yl each optionally substituted by amino, imino and/or by oxo, and R3 represents carboxy, 4-nitrobenzyloxycarbonyl, lower alkenyloxycarbonyl, or ethoxycarbonyl substituted in the 2-position by lower alkylsulphonyl, cyano or by tri-lower alkylsilyl, or an esterified carboxy group that can be cleaved under physiological conditions, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of such compounds of the formula I having a salt-forming group. 5. Compounds of the formula I according to claim 3 in which Rj and R^ have the meanings given in claim 4 and R2 represents 1-pyrrolyl or dihydro-1-pyrrolyl optionally substituted by lower alkyl or by halogen, imidazol-I-yl or pyrazol-1-yl optionally substituted by lower alkyl, amino-lower alkyl, amino or by nitro, 1,2,3-, 1,2,4- or 1,3,4-triazol-1-yl optionally substituted by lower alkyl, carboxy-lower alkyl or by phenyl, 1- or 2-tetrazolyl optionally substituted by lower alkyl, carboxy-lower alkyl, sulpho-lower alkyl, di-lower alkylamino-lower alkyl, amino or by optionally halo-substituted phenyl, dihydro-1-pyridyl that is unsubstituted or substituted by oxo and optionally additionally substituted by halogen, dihydro- or tetrahydro-1 -pyrimidyl that is unsubstituted or substituted ff^

1 2107 23 94 by oxo and optionally additionally substituted by lower alkyl, amino, di-lower alkylamino and/or by carboxy, dihydro- or tetrahydro-1,2,4- or -1,3,6-triazin-1-yl, each of which is optionally substituted by lower alkyl, lower alkoxy, amino and/or by up to 2 oxo groups, indol-1-yl, benzimidazol-1-yl, benzotriazol-1-yl, pyridopyrrol-1-yl, pyridoimidazol-1-yl, or pyrimido-, dihydropyrimido- or tetrahydropyrimido-imidazol-1-yl each optionally substituted by amino, imino and/or by oxo, or pyrimido-, dihydropyrimido- or tetrahydropyrimido-1,2,3-triazol-1-yl each optionally substituted by amino, imino and/or by oxo, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of such compounds of the formula I having a salt-forming group. 6. Compounds of the formula I according to claim 2 in which Rj represents lower alkyl substituted in the a-position by hydroxy, R2 represents pyrrol-1-yl that is unsubstituted or substituted by lower alkyl or by halogen, pyrazol-1-yl that is unsubstituted or substituted by lower alkyl or by amino-lower alkyl, imidazol-1-yl that is unsubstituted or substituted by lower alkyl, lower alkoxy, amino-lower alkyl, lower alkanoylamino-lower alkyl, amino-carboxy-lower alkyl, amino-lower alkoxycarbonyl-lower alkyl, carboxy-lower alkyl, lower alkoxycarbonyl-lower alkyl, carbamoyl-lower alkyl, carbamoyloxy-lower alkyl, hydroxy-lower alkyl, lower alkanoyloxy-lower alkyl, halo-lower alkyl, lower alkylthio-lower alkyl, amino or by nitro, 1,2,4-or 1,3,4-triazol-l-yl that is unsubstituted or substituted by lower alkyl, indol-l-yl, benzimidazol-1-yl, benzotriazol-l-yl, IH-pyrrolo(2,3-b)pyrid-l-yl, IH-imidazo(4,5-b)-pyrid-l-yl or purin-l-yl; or 1- or 2-tetrazolyl, each of which is unsubstituted or 210 95 substituted by lower alkyl, amino or by phenyl, and R3 represents carboxy or esterified carboxy that can be cleaved under physiological conditions, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of such compounds of the formula I containing a salt-forming group. 7. Compounds of the formula I according to claim 3 in which Rj represents lower alkyl substituted in the ct-position by hydroxy or by tri-lower alkylsilyloxy, R2 represents pyrrol-1-yl that is unsubstituted or substituted by lower alkyl or by halogen, imidazol-1-yl that is unsubstituted or substituted by lower alkyl, amino-lower alkyl, amino or by nitro, pyrazol-1-yl, or 1,2,4- or 1, 3, 4-triazol-1-yl that is unsubstituted or substituted by lower alkyl, 1- or 2-tetrazolyl each of which is unsubstituted or substituted by lower alkyl, amino or by phenyl, indol-l-yl, benzimidazol-l-yl, benzotriazol-l-yl, 1H— pyrrolo(2,3-b)pyrid-l-yl, IH-imidazo(4,5-b)pyrid-l-yl or purin-l-yl, R3 represents carboxy, lower alkenyloxycarbonyl or esterified carboxy that can be cleaved under physiological conditions, optical isomers of compounds of the formula I, mixtures of these optical isomers, and salts of such compounds of the formula I containing a salt-forming group. 8. Compounds of the formula I according to claim 2 in which R] represents hydroxymethyl or 1-hydroxy-ethyl, R2 represents pyrrol-1-yl, imidazol-1-yl that is unsubstituted or substituted by lower alkyl, lower alkoxy, amino or by amino-lower alkyl- nvraini-i-«i that is unsubstituted or substituted 210728 - 96 - by amino-lower alkyl, 1,2,4-triazol-1-yl, or tetrazol-1 -yl that is unsubstituted or substituted by amino, and R3 represents carboxy or esterified carboxy that can be cleaved under physiological conditions, optical isomers of compounds of the formula I in which represents 1-hydroxyethyl, mixtures of these optical isomers, and salts of compounds of the formula I. 9. Compounds of the formula I according to claim 3 in which Rj represents hydroxymethyl or 1-hydroxyethyl, R2 represents pyrrol-J-yl, imidazol-1-yl that is unsubstituted or substituted by amino or by amino-lower alkyl, pyrazol-1-yl, 1,2,4-triazol-1-yl, tetrazol-1-yl, which is unsubstituted or substituted by amino, benzimidazol-l-yl or IH-pyrrolo(2,3-b)-pyrid-l-yl, and R^ represents carboxy, and optical isomers of compounds of the formula I in which R^ represents 1-hydroxyethyl, mixtures of these optical isomers, and salts of such compounds of the formula I. 10. Compounds of the formula I according to claim 2 in which Rj represents hydroxymethyl or {1R) — 1 — hydroxyethyl, R2 represents imidazol-1-yl that is unsubstituted or substituted by lower alkyl or by amino-lower alkyl, and R3 represents carboxy or esterified carboxy that can be cleaved under physiological conditions, and salts of compounds of the formula I. 11. Compounds of the formula I according to claim 3 ^ in which Rj represents hydroxymethyl or (1R) — I — ^ hydroxyethyl, R2 represents imidazol-1 -yl, pyrazol-1*^' » ^ -r Tm ^-3SEP»87<>i 21U7 - 97 - yl or 1,2,4-triazol-1-yl, and R3 represents carboxy, and salts of such compounds of the formula I. 12. Pharmaceutically acceptable salts of compounds of the formula (I) according to claim 2. 13. Pharmaceutically acceptable salts of compounds of the formula (I) according to claim 3. 14. Esters of compounds of the formula I according to claim 3 that can be cleaved under physiological conditions. 15. Esters of compounds of the formula I according to claim 2 that can be cleaved under physiological conditions. 16. (5R,6S)-2-(imidazol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 3. 17. (5R, 6S) -2- (imidazol-1 -yl) -6- [ (1 *R)-hydroxyethyl] -2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 3. 18. (5R,6S)-2-(4-methylimidazol-1-yl)-6-hydroxymethyl-2-panem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 3. 19. (5R,6S)-2-(4,5-dimethylimidazol-1-yl)-6-hydroxy-methyl-2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 2. 20. (5R,6S)-2-[4-(2-aminoethyl)-imidazol-1-yl]-6-hydroxymethyl-2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 2. - 98 - 21Q72S 21. (5R,6S)-2-[4-methoxyimidazol-1-yl]-6-hydroxy-methyl-2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 2. 22. (5R,6S)-2-[4-aminomethyliraidazol-1-yl]-6-hydroxy-methyl-2-penem-3-carboxylic acid and pharmaceutically acceptable salts thereof according to claim 2. 23. (5R, 6S) -2- (imidazol-1 -yl) - 6- [ (1 R)-1 -hydroxyethyl] -

2-penem-3-carboxylic acid acetoxymethyl ester according to claim 2. 24. A compound of the formula I according to claim 2 selected from the group comprising (5R,6S)-2-(1,2,4-triazol-1 -yl)-6-hydroxymethyl-2-penem-

3-carboxylic acid, (5R, 6S)-2-(pyrazol-1 -yl) -6-hydroxymethyl-2-penem-3-carboxylic acid, (5R,6S)-2-(pyrrol-1-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid and (5R,6S)-2-(

4-methylpyrazol-l-yl)-6-hydroxymethyl-2-penem-3-carboxylic acid. 25. A compound according to claim 3 and its pharmaceutically acceptable salts for use in a method for the therapeutic treatment of the human or animal body. 26. A compound according to claim 2 and its pharmaceutically acceptable salts for use in a method for the therapeutic treatment of the human or animal body. 27. Pharmaceutical preparation containing a compound of the formula I according to claim 3 or a pharmaceutically acceptable salt of such a compound having salt forming groups - 99 - 28. Pharmaceutical preparation containing a compound of the formula I according to claim 2 or a pharmaceuti cally acceptable salt of such a compound having salt-forming groups. 29. Use of compounds of the formula I according to claim 2 and of pharmaceutically acceptable salts of such compounds having salt-forming groups for the manufacture of pharmaceutical preparations. 30. Use of compounds of the formula I according to claim 3 and of pharmaceutically acceptable salts of such compounds having salt-forming groups for the manufacture of pharmaceutical preparations. 31. Process for the manufacture of compounds of the formula I according to claim 1, characterised in that a) an ylide compound of the formula Z I'- 0 (II) -N \c_a. V in which Rj and R2 have the meanings given under formula I and R3' represents a protected carboxy group, Z represents oxygen or sulphur and X® represents either a tri-substituted phosphonio group o a di-esterified phosphono group together with a cation, is cyclised, or 210 100 b) a compound of the formula R 1 /S—C—R II 2 z \ N (III), O C=0 in which Rj and R2 have the meanings given under formula I, Z has the meaning given under formula II and R3' represents a protected carboxy group, is treated with an organic compound of trivalent phosphorus, or c) a compound of the formula in which Rj has the meaning given under formula I, R-j' represents a protected carboxy group and Y represents a group that can be replaced by nucleophilic reaction, is reacted with a compound that introduces the radical R2, and, if desired or necessary, in a resulting compound of the formula I a protected hydroxy group in the radical Rj is converted into a free hydroxy group, and/or, if desired, in a resulting compound of the formula I a protected carboxy group R31 is converted into a free carboxy group, into an esterified carboxy group that can be cleaved under physiological 210723 - 101 - conditions or into a different protected carboxy group 1*3*, or a free carboxy group R3 is converted into an esterified carboxy group that can be cleaved under physiological conditions or into a protected carboxy group r31, and/or, if desired, other protected functional groups contained in the radical R2 are converted into free functional groups, and/or, if desired, in a resulting compound of the formula I a radical R2 is converted into a different radical R2, and/or, if desired, a resulting compound having a salt-forming group is converted into a salt, or a resulting salt is converted into a free compound or into a different salt, and/or, if desired, a resulting mixture of isomeric compounds is separated into the individual isomers. 32. Process for the manufacture of compounds of the formula I according to claim 1, characterised in that a) an ylide compound of the formula Z R lo S—C—R (II) , : n I R3 in which Rj and R2 have the meanings given in claim 1, R->' represents a protected carboxy group, Z represents oxygen or sulphur and Xw represents either a tri-substituted phosphonio group or a di-esterified phosphono group together with a cation, is cyclised, or l t I'l j- X o /" c ~r3SEP1987 210728 102 b) a compound of the formula (III)/ N 0 / \ c=o I in which Rj and R2 have the meanings given in claim 1, Z represents sulphur and * represents a protected carboxy group, is treated with an organic compound of trivalent phosphorus, and, if desired or necessary, in a resulting compound of the formula I a protected hydroxy group in the radical Rj is converted into a free hydroxy group, and/or, if desired, in a resulting compound of the formula 1 a protected carboxy group Rj' is converted into a free carboxy group, into an esterified carboxy group that can be cleaved under physiological conditions, or into a different protected carboxy group ', and/or, if desired, other protected functional groups contained in the radical R2 are converted into free functional groups, and/or, if desired, in a resulting compound of the formula I a radical R2 is converted into a different radical R2, and/or, if desired, a resulting compound having a salt-forming group is converted into a salt, or a resulting salt is converted into a free compound or into a different salt, and/or, if desired, a resulting mixture of isomeric compounds is separated into the individual isomers. 33. A compound of the formula I as defined in claim 1 if manufactured according to the method of claim 31. 210723 103 34. A compound of the formula I as defined in claim 1 if manufactured according to the method of claim 32. 35. A compound of the formula I as defined in claim 1 substantially as herein described. 36. A method for the manufacture of a compound of the formula I as defined in claim 1 substantially as herein described. 37. The pure optical isomers of compounds of the formula I set out in claim 1 substantially as herein described. 38. A pharmaceutical preparation containing a compound of formula I as defined in claim 1 substantially as herein described. 39. Pharmaceutically acceptable salts of a compound of formula I as defined in claim 1 substantially as herein described. 40. An ester of a compound of formula I as defined in claim 1 substantially as herein described. CIBA-GEIGY AG. F0 7.4 UL/hc* ai r3SEPIW: </div>