MXPA98000067A - Derivatives of propiophenone and procedure for the preparation of the mis - Google Patents

Abstract

A propiophenone derivative of the formula (I): wherein OX is a hydroxy group that can be optionally protected, Y is a lower alkyl group, and Z is a D-glucopyranosyl group in which one or more hydroxy groups can be optionally protected, or a pharmaceutically acceptable salt thereof, said compounds have excellent hypoglycemic activity so they are useful in the prophylaxis or treatment of diabetes.

Description

DERIVATIVES OF PROPIOFENONfl AND PROCEDURE PñRfl Lfl PREPARATION OF THE SAME TECHNICAL FIELD The present invention relates to a novel propiophenone derivative having a hypoglyceric activity, and to a process for preparing the same.

BACKGROUND OF THE INVENTION Although diet therapy is essential in the treatment of diabetes, when diet therapy does not sufficiently control the conditions of patients, insulin or an oral antidiabetic drug is usually used. Anti-diabetics composed of biguad na and sul fomlurea compounds have been used. However, these antidiabetics have several side effects. For example, the biguanide compounds cause lactic acidosis and the sulfonylurea compounds cause significant hypoglycemia. Under these circumstances, it has been desired to develop novel drugs for the treatment of diabetes that do not have such side effects. Recently, it has been reported that hyperglyceria participates in the onset and progressive deterioration of diabetes, that is, the theory of glucose toxicity. That is, chronic hyperglyceria leads to decreased insulin secretion and contributes to increased resistance to insulin and, as a result, the blood glucose concentration increases in such a way that diabetes is self-exacerbated. Cver, 5 Diabetologia, Vol. 28, p . 119 (1985); Diabetes Care, vol. 13, p. 610 (1990), etc.3. Therefore, the aforementioned self-exacerbation cycle is interrupted by treatment of hyperglyceria, so that prophylaxis or treatment of diabetes is possible. 10 As one of the methods to treat hyperglyceria, excretion of an excess amount of glucose directly into the urine was considered, in order to normalize the blood glucose concentration. Florizine is a glycoside that exists in barks and stems of Rosaceae (for example apple, pear, etc.). Recently, it has been found that florizine is an inhibitor of the Na + -glucose cotransporter that exists only in the chorionic membrane of the intestine and the kidney, and inhibiting the Na + -glucose cotransporter, florizine? 20 inhibits the renal tubular reabsorption of glucose and promotes the excretion of glucose in such a way that the level of glucose in the plasma is controlled. Based on this action of florozin, when the plasma glucose level of diabetic animals is controlled at a normal level for a long period by the After daily subcutaneous administration of florizine, conditions in diabetic animals are improved to normal [see Journal of Clinical Investigation, Vol 79, p 1510 (1987), ib. Vol .. 80, p.1037 (1987 ), ib. Vol. 87, p. (1991), etc.], However, when flopzine is administered orally, it is mostly hydrolysed to produce - 5 glucose and floretin, which is the agiicon of florizma, and therefore, the amount of flopzin to be absorbed is so small that the effect of the florizm on the excretion of glucose in the urine is very weak. In addition, it is known that the floretma, which is the agi i with flopz na, strongly inhibits a transporter from glucose of diffusion type facilitated. For example, when floretine is administered intravenously to rats, the concentration of glucose in the brains of rats decreases Cver Stroke, Vol.14, p. 388 (1983)]. Therefore, when the flopzma is administered over a long period, there may be adverse effects on various tissues and therefore, the florizma has not been used as an antidiabetic.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide a derivative of 4'-alk? Lpro ?? ofenone inferior that shows an activity of increase of glucose in the urine because it inhibits the renal tubular reabsorption of glucose and shows an excellent hipoglicernica activity and at the same time, your agl with has a very weak inhibitory activity of the facilitated diffusion-type glucose transporter. Another object of the present invention is to provide a process for preparing a propiophenone derivative of the present invention. A further object of the present invention is to provide a hypoglycemic agent comprising as an active ingredient a propiophenone-5 derivative of the present invention, or a pharmaceutically acceptable salt of the same.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a propiophenone derivative of the formula I: wherein OX is a hydroxyl group which may be optionally * 20 protected, Y is a lower alkyl group, and Z is a group (3-D-glucopyranosyl in which one or more hydroxyl groups may be optionally protected, or a pharmaceutically salt acceptable of the same Among the compounds (I) of the present invention, in In the case where OX of the formula I is a protected hydroxyl group, the protecting group may be any protecting group which may be a protecting group for a phenolic hydroxyl group, for example, a lower alkoxy-lower alkyl group such as a group rnetox unet i lo; a gruÃ'o ali Jo; and an acyl group such as a lower alkanoyl group, a lower alkoxy lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxy lower alkoxycarbonyl group, an aplcarbonyl group (for example benzoyl group). Among these protecting groups, preferred are an acyl group such as an alkanoyl group, a lower alkoxy-lower alkane group, a lower alkoxycarbonyl group, a lower alkoxy-lower alkoxycarbonyl group, and a lower alkanoyl group is especially preferred. , and a lower alkoxycarbonyl group. Among the compounds (I) of the present invention, in the case where Z of the formula I is a β-D-glucopyranosyl group in which one or more hydroxyl groups are protected, the protecting group may be any conventional protecting group for hydroxyl groups that can be easily removed by a conventional method such as acid treatment, hydrolysis, reduction, etc. The β-D-glucopyranosyl group in which one or more hydroxyl groups are protected by the aforementioned protecting groups can be selected from (i) a β-D-glucopyranosyl group in which one or more hydroxyl groups are acylated, di) a ß-D-glucopyranosyl group in which the hydroxyl groups combine to form a 1-alkoxyl group? lower-lower alkylidenedioxy, a benzylidenedioxy group, a phosphinic dioxy group, or a carbonyldioxy group together with protecting groups thereof, and (iii) a β-D-glucopyranosyl group in which one or two hydroxyl groups are acylated, and the other two hydroxyl groups combine to form a lower 1-lower alkoxy-lower alkylenedioxy group, a benzylidenedioxy group, a phosphinic-dioxy group, or a carbonyldioxy group together with the protecting groups thereof. However, it should not be considered that the protecting groups for the hydroxyl groups of the β-D-glucopyranosyl group are limited to the above protecting groups, and can be any that can be removed after administering the present compound in the living body and give the hydroxyl groups of the β-D-glucopyranosyl group, or which may promote the absorption of the desired compound in the living body, or make it easier to administer the present compound in the living body, or which may increase the solubility in oil and / or water of the present compound. When the hydroxyl group of the β-D-glucopyranosyl group is acylated, the acyl group is preferably a lower alkanoyl group, a lower alkoxy-lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxy-lower alkoxycarbonyl group, or an arylcarbonyl group ( for example benzoyl group), or an amino acid residue that is obtained by removing a hydroxyl group of the carboxyl group of a corresponding amino acid (in which the arnino groups and / or the carboxyl groups and / or the hydroxyl groups in said residue can be protected by means of a conventional protective group). The amino acid residue includes a group that is obtained by removing a hydroxyl group from the carboxyl group of a natural amino acid such as aspartic acid, glutamic acid, glutamine, serine, sarcosine, proline, phenylalanine, leucine, isoleucine, glycine, tryptophan, cysteine, histidine, tyrosine or valine, or an antipode thereof, or a racemic compound thereof. When Z is a β-D-glucopyranosyl group in which two hydroxyl groups of the β-D-glucopyranosyl group combine to form a lower 1-lower alkoxy-lower alkylidenedioxy group, a benzylidenedioxy group, a phosphinic dioxy group, or a carbonyldioxy group together with the protecting groups thereof, said β-D-glucopyranosyl group can be a β-D-glucopyranosyl group in which the 4- and 6-hydroxyl groups of the β-D-glucopyranosyl group combine to form a 1- group lower alkoxy-lower alkylidenedioxy, a benzylidenedioxy group, a phosphinic-dioxy group, or a carbonyldioxy group together with the protecting groups thereof. Said β-D-glucopyranosyl group has the formula: where one of R? and R8 is a hydrogen atom or a lower alkyl group, and the other is a lower alkoxy group, or one of R7 and R1 is a hydrogen atom, and the other is a phenyl group, or R? and R8 combine to form an oxo group. When two hydroxyl groups of the β-D-glucopyranosyl group combine to form a lower 1-alkoxy lower alkyldidenedioxy group together with the protecting groups thereof, the lower 1-lower alkyloxy loweridenedioxy group is preferably a 1-alkoxyethylidenedioxy group. lower, and most preferably a 1-methoxyethylidenedioxy group or a 1-ethoxyethidenedioxy group. And of the formula (I) is preferably an alkyl group having from 1 to 4 carbon atoms, preferably preferably a methyl group or an ethyl group. Representative compounds of the present invention are the compounds of the formula (I) wherein Z is a β-D-glucopyranosyl group in which one or more hydroxyl groups may be optionally acylated by a group selected from a lower alkanoyl group, an alkoxycarbonyl group lower, a lower alkoxy-lower alkanoyl group and a lower alkoxy-lower alkoxycarbonyl group, or a β-D-glucopyranosyl group in which two hydroxyl groups combine to form a lower 1-lower alkoxy-alkyldidenedioxy group or a phosphinic-dioxy group together with the protective groups of the same. More specifically, the representative compounds of the present invention are the compounds of formula (I) wherein Z is a β-D-glucopyranosyl group wherein the 2-hydroxyl group, or the 2- and 3-hydroxyl groups or the group 4 -hydroxyl, or the 6-hydroxyl group may be optionally acylated by means of a group selected from a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxy-lower alkanoyl group, and a lower alkoxy-lower alkoxycarbonyl group, or a group β-D-glucopyranosyl, wherein the 4- and 6-hydroxyl groups combine to form a lower 1-lower alkoxy-lower alkylidenedioxy group or a phosphinic dioxy group together with the protecting groups thereof. Among the compounds (I) of the present invention, the preferred compounds are the compounds of formula (I) wherein OX is a hydroxyl group, a lower alkanoyloxy group, or a lower alkoxycarbonyloxy group, Z is a β-D-glucopyranosyl group , a 2-0- (lower alkanoyl) -β-D-glucopyranosyl group, a 2, 3-di-0- (lower alkanoyl) -β-D-glucopyranosyl group, a 4-0- (lower alkoxycarbonyl) group - β-D-glucopyranosyl, a 6-0- (lower alkanoyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxy group -alkyl lower) -β-D-glucopyranosyl, a 6-0- (lower alkoxy-lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 4,6-0- (1-lower alkoxy-lower alkylidene) -β group -D-glucopyranosyl or a 4,6-O-phosphinic-β-D-glucopyranosyl group. The preferred compounds rnuy are the compounds of formula (I) wherein OX is a hydroxyl group or a lower alkanoyloxy group, Z is a β-D-glucopyranosyl group, a 2, 3-di-0- (lower alkanoyl) group - β-D-glucopyranosyl, a 4-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a group 4, 6-0- (1 lower alkoxy-lower alkylidene) -β-D-glucopyranosyl or a 4,6-0-phosphinic-β-D-glucopyranosyl group. Among the present compounds (I), the preferred compounds are the compounds of formula (I) wherein OX is a hydroxyl group, Y is a methyl group or an ethyl group, Z is a β-D-glucopyranosyl group, a 4-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 4,6-0 ~ (l-lower alkoxy-lower alkylidene) group -β-D-glucopyranosyl or a 4,6-0-phosphinic-β-D-glucopyranosyl group. Especially preferred compounds are the compounds of formula (I) wherein Z is a β-D-glucopyranosyl group or a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group. The propiophenone derivatives (I) of the present invention can be used for the purposes of the present invention either in the free form or in the form of a pharmaceutically acceptable salt thereof. The pharmaceutically acceptable salt can be an alkali metal salt (e.g., the sodium salt), a salt with an inorganic acid (for example, hydrochloride), or a salt with an organic acid (for example, tosylate). The propiophenone derivatives (I) of the present invention or a pharmaceutically acceptable salt thereof also include an intramolecular salt thereof, or a solvate or hydrate thereof. The compounds (I) of the present invention or a pharmaceutically acceptable salt thereof can be administered either orally or parenterally, and can be formulated in a pharmaceutical preparation in admixture with a pharmaceutically acceptable carrier or diluent suitable for oral administration or parenteral administration. The pharmaceutically acceptable carrier or diluent can be, for example, binder (for example syrup, gum arabic, gelatin, sorbitol, tragacanth, polyvinyl pyrrolidone, etc.) excipient (for example lactose, sucrose, corn starch, potassium phosphate, sorbitol, glycerin, etc.) lubricant (eg, magnesium stearate, talc, polyethylene glycol, silica, etc.) disintegrant (eg, potato starch, etc.), wetting agent (eg, sodium lauryl sulfate, etc.), and the like . These pharmaceutical preparations may be in the form of a solid preparation such as tablets, granules, capsules, powders, etc., or in the form of a liquid preparation such as a solution, suspension, emulsion, etc. when administered orally. When administered parenterally, the pharmaceutical preparations may be in the suppository form, an injection preparation or an intravenous drip preparation using distilled water for injection, a physiological saline solution, an aqueous glucose solution, etc. The dose of the propiophenone derivative (I) or a pharmaceutically acceptable salt of the same varies depending on the routes of administration, age, weight and condition of the patient, or the severity of the diseases to be cured, but may be on the scale of 0.05 to 30 rng / kg / day, preferably in the range of 0.5 to 15 rng / kg / day, in the case of oral administration. In the case of parenteral administration, the dose of the present compound (I) can be in the range of 0.005 to 30 rng / kg / day, preferably in the range of 0.05 to 3 rng / kg / day. The desired compound (I) of the present invention can be prepared by reducing a compound of the formula (II): wherein the symbols are the same defined above, and if necessary, continue with the conversion of the product into a pharmaceutically acceptable salt thereof. The reduction reaction can be carried out by a conventional method such as reduction with a metal hydride, catalytic reduction, etc. For example, reduction with a metal hydride can be carried out using a metal hydride in a solvent, and the catalytic reduction can be carried out using a ba catalyst or atmospheric pressure of hydrogen gas in a solvent. In the catalytic reduction, the catalyst may be any conventional, for example, palladium-carbon, platinum-carbon, platinum oxide, Raney nickel. To prevent over-reduction of the double bond of the benzofuran ring, a substance can be added which can reduce the catalytic capacity of the catalyst, for example amines such as 4- (N, N-di-diallylamino)? Iridine, N, Nd? Methylaniline, aniline, dipropylamine, diisopropylarnine, morpholine, piperazine, dicyclohexylanine, piperidine, pyrrolidine, or amides such as N, N-dimethylacetamide. In reduction with a metal hydride, the metal hydride can be any that can reduce a carbon-carbon double bond. However, it may be preferable to use metal hydrides that do not reduce an acetone, for example, sodium hydride and tellurium (NaTeH), which is prepared according to the method described in? Ynthesis, p. 545 (1978). Sodium hydride and tellurium is usually used in an amount of 1 to 3 equivalent rnmoles, preferably in an amount of 1 to 1.5 equivalent equivalents, to 1 mole equivalent of compound (II). In the reduction reaction, the solvent may be any which does not disturb the reaction, for example, an organic solvent such as alcohols (for example methanol, ethanol), ethers (for example, tetrahydrofuran), esters (for example ethyl acetate). , organic acids (eg, acetic acid), or a mixture of these organic solvents and water. The reduction reaction can be carried out from a temperature under cooling to a temperature with heating, preferably at a temperature of 10 ° C to 30 ° C. The compounds (I) of the present invention thus obtained can be converted to one another by the following methods, or a combined process thereof. (1) Among the present compounds (I), the compound of the formula (I-b): wherein R1 is an acyl group, and the other symbols are the same as defined above, can be prepared by acylating the compound of the formula (I-) a of the present invention: where the symbols are the same as defined above. (2) Among the present compounds (I), the compound of the formula (I-c): wherein R3 is an acyl group, and the other symbols are the same as defined above, it can be prepared by acylating a compound of the formula (Id), which is a compound of the formula (Ia) wherein the 4- and 6-hydroxyl groups of the ß-D-glucopyranosyl group are protected: wherein R ^ O and R2 or are protected hydroxyl groups, and the other symbols are the same as defined above, followed by removal of the protecting groups of the product, i.e., Rii and R2i. * D (3) Among the present compounds (I), the compound of the formula (I-e): where R ^ is an acyl group, and the other symbols are the same defined above, can be prepared Acylating a compound of the formula (I-f), which is a compound of the formula (I-d) wherein the 3-hydroxyl group of the β-D-glucopyranosyl group is also protected: where R3 G is a protected hydroxyl group, and the Other symbols are the same as defined above, followed by removal of the protective groups of the product, ie, Rll, R21 and R31"In the compounds (Id) and (If), the protective groups Rll, 2 and R31 for the groups hydroxyl of the group ß-D-glucopi anosyl can be any conventional, and the protecting groups for the 4- and 6-hydroxyl groups are preferably those which can be combined with each other to form a benzylidene group, etc. The protecting group for the 3-hydroxyl group is preferably a lower triacylsilyl group (for example, t-butyldimethylsilyl group, trirnethylsilyl group). The removal of these protecting groups is carried out by means of a conventional method such as acid treatment, hydrolysis, reduction, etc. The acylation reaction of the above processes (1), (2) and (3) is carried out by reacting the starting compound with an organic acid (for example a lower alkanecaboxylic acid such as acetic acid, a lower alkoxy acid lower alkylcarboxylic acid such as rnetoxyacetic acid, benzoic acid, etc.) corresponding to the desired acyl group, or a salt of the ism, or a reactive derivative of the ism. The reaction between the corresponding organic acid with the desired acyl group, or a salt of the same, and the starting compound, is carried out in a suitable solvent in presence or absence of a condensing agent. The reaction between the reactive derivative of the organic acid and the starting compound is carried out in a suitable solvent or without a solvent, in the presence or absence of an acid receptor. The salt of the organic acid includes, for example, an alkaline metal salt or an alkaline earth metal salt such as «5 sodium salt, potassium salt, calcium salt, etc. When these organic acid salts are used for the reaction of < Condensation, these salts may preferably be used after being prepared to be in the form of a free acid. The reactive derivative of organic acid includes Examples include an acid halide, acid anhydride, active ester, or an active amide of a lower alkanecarboxylic acid, lower alkoxy mfepor-lower alkane carboxylic acid, lower alkoxy carboxylic acid, benzoic acid, etc. The condensing agent can be any Conventional, for example, dicyclohexylcarbodurnide, diethyl cyanophathate, carbonyldurnidazole, bis (2-oxo-3-oxazole? D? N? 1) phosphinic chloride, etc. The acid acceptor can be any conventional, for example an inorganic base such as a alkaline metal hydroxide (for example sodium hydroxide, potassium hydroxide, etc); an alkaline metal carbonate (for example potassium carbonate, sodium carbonate, etc); an alkaline metal acid carbonate (for example, sodium acid carbonate, potassium acid carbonate, etc.); a metal hydride Alkaline (for example sodium hydride, potassium hydride, etc.), or an organic base such as a lower tpalkylanine (for example, triethylamine, diisopropylethylamine, etc.); pyridine; 2,4,6-collidine; 4- (N, W-direthylarnino) pyridine; quinuclidine, aniline; N, N ~ dirnetilaniline, etc. The solvent may be any conventional one that does not disturb the reaction, eg, water; esters (for example ethyl acetate); halogenated hydrocarbons (for example, dichloromethane); amides (for example dimethyl formamide); ethers (for example tetrahydrofuran); nitriles (for example acetonitrile); etc, or a mixture thereof. In addition, an organic base such as pyridine, 2,4,6-collidine, etc., which were previously exemplified as acid receptors, can also be used as the solvent. The reaction can be carried out from a temperature under cooling to a temperature with heating, preferably at a temperature of -10 ° C to 100 ° C, especially at a temperature of 0 ° C to 50 ° C. In the above process (1), the compound of the formula (I-b), wherein R 1 is a lower alkoxycarbonyl group can be prepared by a modified method described in "20 3. Chern. Soc. Perkin Trans. 1 p. 589 (1993), that is, by reacting the compound (I-a) with the lower dialkyl carbonate in the presence or absence of molecular sieves in a suitable solvent using a lipase. The lipase can preferably be a lipase derived from Candida Antarctica, for example, Novozyrn 435 (manufactured by Novo Nordisk fl / S).

The solvent may be any conventional which does not disturb the reaction and preferably are ethers such as dioxane, ethylene glycol diethyl ether, etc. The compound (I-a) is prepared by reducing the * 5 compound of formula (II) wherein Z is a β-D-glucopyranosyl group, and compound (Ia) is useful as one of the compounds of the present invention, as well as a synthetic intermediate for the preparation of other compounds of the present invention. 10 The compound (I-d) is prepared by protecting the groups 4- and 6-hydroxyl of the ß-D-glucopyranosyl group of the compound (I-a). The compound (I-f) is prepared by protecting the 3-hydroxyl group of the β-D-glucopyranosyl group of the compound (I-d). The protection of the hydroxyl groups of the β-D-15-glucopyranosyl group is carried out by a method which is described later in the process (5), or by means of the methods described in the examples, or a conventional method. In the acylation reaction of the procedures * 20 above (1), (2) and (3), when OX of the starting compounds is a hydroxyl group, the OX may also be optionally acylated, and the product so obtained, ie the product in which OX it is acylated, it is also included in the present invention. When OX of the starting compounds must not be acylated, the product in which OX is acylated in a suitable solvent (for example tetrahydrofuran, rnetanol, water, etc.) is treated with such a base or an alkali metal acid carbonate (for example sodium hydrogen carbonate, acid carbonate of potassium, etc), amines (for example, t-butylannine, etc.) to remove the acyl group from the product. (4) Among the compounds (I) of the present invention, the compound of the formula (I-g): wherein R2 is a lower alkyl group, and the other symbols are the same as defined above, can be prepared by reacting a compound of the formula (I-h): wherein the symbols are the same as defined above, with a compound of formula III: R20H (III) wherein R2 is the same as defined above.

The reaction is carried out in a suitable solvent in the presence or absence of an acid catalyst. The compound (III) can be a straight chain or branched chain alkanol having 1 to 6 carbon atoms such as methanol, ethanol, propanol, isopropanol, n-butanol, t-butanol, etc., and is preferably used in a equimolar amount or in a slightly excess amount, to the amount of the compound (Ih). The solvent can be any that does not disturb the reaction, for example, hydrogenated hydrocarbons (for example dichloromethane, dichloroethane, chloroform, etc.). The compound (III) per se can be used as a solvent. The acid catalyst includes, for example, organic acids such as arylalic acid (eg p-toluenesulfonic acid), a lower alkanesulfonic acid (eg, methanesulfonic acid, ethanesulfonic acid), a lower alkanecarboxylic acid (eg, acetic acid), or an inorganic acid such as hydrochloric acid, sulfuric acid. The reaction is carried out from a temperature under cooling to a temperature with heating, preferably at a temperature of 25 ° C to 50 ° C, especially at a temperature of 25 ° C to 35 ° C. In addition, the compound (I-h) can be prepared by (a) reacting the compound (I-a) with an aryl halogenoformate (e.g., p-nitrophenyl halogenoformate), or N, N-carbonyldiimidazole, etc., in a solvent or without solvent in the presence or absence of an acid acceptor, if necessary, under heating; or (b) by the method (5) described below. In the above (a), the solvent can be any that does not disturb the reaction, for example, tetrahydrofuran, dichloromethane, chloroform, etc. The acid acceptor includes, for example, an organic base (eg, 2,4,6-collidine, pyridine, 2,6-lutidine), or an inorganic base (eg, sodium acid carbonate). When an organic base is used as an acid acceptor, the organic base per se can be used as a solvent. The reaction is carried out from a temperature under cooling to a temperature with heating, especially at a temperature of -50 ° C to 60 ° C. When aryl halogenofornate is used in the reaction, it is preferable to heat the reaction system after add to it the aryl halogenofornate, especially it is preferred to heat it from 40 ° C to 70 ° C. (5) Among the present compounds (I), the compound of the formula (I-i): wherein RS is a hydrogen atom or a lower alkyl group and R6 is a lower alkoxy group, or R5 is a hydrogen atom and R6 is a phenyl group, or R5 and R6 can be combined to form an oxo group, and the others symbols are the same defined above, can be prepared by reacting a compound of the formula (Ia) with a compound of the formula (IV): RS Al \ / C (IV) / \ R6 A2 where fli and fl2 are leaving groups, and the other symbols are the same defined above. In the compounds (IV), the leaving group can be any conventional one which does not disturb the reaction, for example, a halogen atom (for example, chlorine atom, bromine atom), and a lower alkoxy group (for example rnetoxy, ethoxy). The reaction is carried out in a suitable solvent or without a solvent in the presence or absence of an acid or a base. The solvent can be any that does not disturb the reaction, for example, halogenated hydrocarbons (e.g., dichloromethane, chloroform, dichloroethane, etc.), ethers (e.g., tetrahydrofuran, diethyl ether, etc.), or it can also be used as solvent an excess amount of the compound (IV) "The acid includes for example an organic acid such as arylsulfonic acid (for example, p-toluenesulfonic acid), a lower alkanesulfonic acid (for example, methanesulfonic acid, ethanesulfonic acid, etc.). ), trifluoroacetic acid, etc., or an inorganic acid such as hydrochloric acid, sulfuric acid, etc., or a salt of a strong acid and a weak base such as pyridinium p-toluensulfonate. The base includes, for example, a lower tri-alkylamino (e.g., triethylanine, diisopropylethylamine), pyridine, 4- (N, N-dirnethylamino) pyridine, aniline, N, N-dirnethylalanine, etc. The reaction is carried out from a temperature under cooling to a temperature with heating, preferably at a temperature of 0 ° C to 50 ° C, especially at a temperature of 20 ° C to 30 ° C. (6) Among the present compounds (I), the compound of the formula (I-j): wherein 0X1 is a protected hydroxyl group, and the other symbols are the same defined above, and the compound of the formula (I-k): where the symbols are the same as those defined above, they can be converted to each other. That is, the compound (I-j) is prepared by protecting the compound (I-k), and the compound (I-k) is prepared by separating the protective group X1 from the compound (I-j). The protection of the compound (Ik) is carried out by a conventional method, for example, when the compound (Ik) is protected with an acyl group, the protection is carried out in the same way as in the previous processes (1) , (2) and (3). When the compound is protected (I-k) with an allyl group, protection is carried out by reacting the compound (I-k) in a suitable solvent (e.g., acetone) in the presence or absence of an acidic receptor (e.g., potassium carbonate) with an allyl halogenide (e.g., allyl bromide). The separation of the protective group Xl from the compound (I-j) is carried out by a conventional method that must be selected according to the types of the protective group to be separated. For example, when 0X is a lower alkanoyloxy or a lower alkanoxycarbonyloxy group, separation of the protecting group is carried out by treating with an acid or a base in a suitable solvent. When OX is an alkoxy lower-alkoxy lower group, separation of the protecting group in a suitable solvent is carried out using an acid. When OXi is an allyloxy group, the separation of the pr-otector group is carried out by treating with a palladium catalyst (e.g., dichlorobis (triphenylphosphine) -palladium (ID) in a suitable solvent (e.g., acetonitrile ) in the presence of an ammonium format. (7) Among the present compounds (I), the compound of the formula (1-1): wherein the symbols are the same as defined above, can be prepared by subjecting a compound of the formula (I-rn) to hydrolysis: wherein R9 and Rio are the same or different and each protecting groups for the hydroxy group, and the other symbols are the same as defined above. The protecting groups R and Rio can be any conventional protecting groups and preferably a phenyl group, a lower alkylene group (e.g., methyl, ethyl), etc. Hydrolysis is carried out by a conventional method, but is preferably carried out in solvent 10 or without solvent in the presence of a base. The solvent can be any that does not alter the reaction, for example, ethers, (e.g., tetrahydrofuran, dioxane, etc.), water or a mixture of these solvents. The base includes, for example, a metal hydroxide. alkaline (e.g., lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), and an alkaline metal carbonate. (e.g., lithium carbonate, sodium carbonate, potassium carbonate, etc.) The reaction is carried out from a temperature in a cold temperature to a temperature with heating, preferably at a temperature of -20 ° C to 50 ° C, most preferably at a temperature of 0 ° C to 0 ° C. When the hydrolysis is carried out using a base, the obtained compound (1-1) is isolated as a salt with the base to be used in the hydrolysis. The compound (I-rn) can be prepared by reacting the compound (I-a) with a compound of the formula (VIII): where A3 is an output group and other symbols are the same as defined above. In the compound (VIII), the leaving group fß can be any conventional one which does not alter the reaction and preferably a halogen atom (e.g., chlorine, bromine). The reaction is carried out in an appropriate solvent or without solvent in the presence or absence of a base. The solvent may be any conventional which does not alter the reaction, for example, halogenated hydrocarbons (e.g., dichloromethane, chloroform, dichloroethane, etc.), ethers, (e.g., tetrahydrofuran, diethyl ether, etc.). base includes, for example, a lower dialkylaniline (e.g., triethylamine, diisopropylethylamine), pyridine, 4- (N, N-direthylarnine) pyridine, aniline, N, N-direthylaniline, 2,4,6-collidine, etc. The reaction is carried out from a cooling temperature or to a temperature with heating, preferably at a temperature of -20 ° C to 50 ° C, preferably preferably at a temperature of 0 ° C to 30 ° C. The starting compound (II) of the present invention can be prepared by condensing a compound of the formula (V). - 5 wherein Z is a β-D-glucopyranosyl group in which the hydroxy groups may be optionally protected and the other symbols are the same as defined above, with 5-forrnylbenzoCb] furan and, if necessary, followed by the protection of the hydroxy groups of the product. When Zl of the starting compound (V) is a β-D-gl-copyranosyl group in which the hydroxy groups are protected, the protecting groups of the hydroxy groups of the β-D-glucopyranosyl group can be any conventional protective group for the hydroxy group, for example, a group Lower alkanoyl (e.g., acetyl group). The condensation reaction of the starting group (V) with 5-forrnilbenzoCb] furan can be carried out with the conventional method, for example, in a suitable solvent (e.g., an organic solvent such as methanol, ethanol, etc.). or a mixture -20 of these organic solvents and water), in the presence of a base (eg, alkali metal oxides such as potassium hydroxide), give a cooling temperature to a temperature with heating (especially at a temperature from 10 ° C to 30 ° C). When the hydroxy groups of the product thus obtained are protected, the protection is carried out by a conventional method or a method described in the processes (1) to (5) above, or a combined process of these processes. The compound (II) obtained in the above process can be used in the reduction reaction of the present invention by purifying to a greater degree, but can be used without purification. The compound (V) for preparing the compound (II) is prepared by condensing a compound of the formula (VI): wherein the symbol is the same as defined above, adding a base in the presence or absence of a quaternary ammonium salt in a suitable solvent to the 2,3,4,6-tetra-0-acetyl-cyclo-D-glucopyranosyl bromide. and, if necessary, followed by the protection of the 6'-phenyl hydroxyl group of the product. The solvent may be one which does not alter the reaction, for example, halogenated hydrocarbons (e.g., chloroform) aromatic hydrocarbons (e.g., toluene), ketones (e.g., acetone), and water. The quaternary ammonium salt may preferably be a tetralkyl-lower-arnonium halide., a lower tetralkylarylonium acid sulfate, a lower benzyltrialkylarylonium halide, etc. Among them, it is especially preferable in benzyltrialkyl ilarylonium chloride. The base includes, for example, an alkaline metal hydroxide (e.g., sodium hydroxide, potassium hydroxide), an alkaline metal carbonate (e.g., potassium carbonate, sodium carbonate), cadmium carbonate. , etc. The reaction is carried out from a cooling temperature to a temperature with heating. The reaction is carried out, for example, (i) by reacting the compound (VI) with 2,3,4,6-tetra-O-acetyl-aD-glucopyranosyl bromide in a suitable solvent (e.g. , aqueous acetone) in the presence of potassium hydroxide and, if necessary, followed by protection of the hydroxy groups of the product, according to the method described in 3. Med. Pharrn. Chem. 5, p. 1045 (1962); or (ii) by refluxing compound (VI) with 2,3,4,6-tetra-O-acetyl-aD-glucopyranosyl bromide in a suitable solvent (e.g., aromatic hydrocarbons such as toluene) in presence of cadmium carbonate and if necessary, followed by protection of the hydroxy groups of the product, according to the method described in Carbohydrate Research, 70, p. 313 (1979)); or (iii) by reacting the compound (VI) with 2,3,4,6-tetra-O-acetyl-aD-gl? copyranosyl bromide in a suitable solvent (e.g., halogenated hydrocarbons such as chloroform or by adding to the same a small amount of water), in the presence of a quaternary ammonium salt (e.g., benzyltimethyl chloride) and an alkali metal carbonate (e.g., potassium carbonate) and, if necessary , followed by protection of the hydroxy groups of the product. The protection of the 6'-phenyl hydroxy group is carried out by a conventional method. The compound of formula (VI) wherein Y is a methyl group is prepared by the method described in 3. Org. Chern. 29 p. 2800 (1964), or acetylating orcinol, or followed by subjecting the resulting orcmol diacetate to the rearrangement of Freís in a suitable solvent (e.g., chlorobenzene) or without solvent in the presence of a Lewis acid (v. ., aluminum chloride). The compound of the formula (VI) wherein Y is a lower alkyl group having two or more carbon atoms is prepared by the following scheme: wherein Y1 is a lower alkenyl group and the other symbols are the same as defined above. That is, the compound (VI) is prepared by the following steps: - 5 (i) converting the 3,5-dirnetoxaniline to a diazonium salt of the same using the sodium nitrite in acetic acid in the presence of a hydrochloric acid and reacting the product with potassium iodide to give dirneto iyodobenzene; 10 (ii) treating the dirnetoxyiodobenzene in acetic acid with hydrobromic acid until de-ingested; (iii) acetylating the hydroxyphenolic groups of the product using acetic anhydride, etc. to give diacetoxyiodobenzene; (Iv) reacting the diacetoxyiodobenzene with tributyl-alkenyl-lower-tin in the presence of a palladium catalyst (e.g., dichlorobis (triphenylphosphine) -palladium (ID) to give the diacetoxy-alkenyl-lower-benzene of the formula (VID; -20 (v) subjecting the compound (VID to catalytic reduction to give the diacetoxy-alkyl-lower-benzene of the formula (VIII); (vi) subjecting the compound (VIII) to the rearrangement of Freis in the presence of a Lewis acid such The aluminum diacetoxy-lower alkylbenzene (VIII) is also prepared as follows.

OCOCH3 OCOCH, (vpi) where the symbols are the same as those defined above. That is, the compound (VIII) is prepared by the following steps: (i) subjecting 3, 5-dirnetoxybenzaldehyde to the Wittig reaction, etc. to give the lower dirnetoxy-alkenylbenzene; (ii) subjecting the lower dirnetoxy-alkenylbenzene resulting in catalytic reduction to give the dirnetoxy-lower alkylbenzene; (iii) treating the dirnetoxy-lower alkylbenzene with hydrobromic acid in acetic acid until de-atylation to give dihydroxy-lower alkylbenzene; (iv) acetylating the lower dihydroxy alkylbenzene with acetic anhydride, etc., to give the compound (VIII). In the present description and claims, the lower alkyl group means a straight chain or branched chain alkyl group having from 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, butyl, etc., preferably those which they have from 1 to 4 carbon atoms. The lower alkoxy group means a straight-chain or branched-chain alkoxy group having from 1 to 6 carbon atoms, for example, rnetoxy, ethoxy, propoxy, butoxy, etc., preferably those having from 1 to 4. carbon atoms. The lower alkanoyl group means a straight-chain or branched-chain alkanoyl group having from 2 to 6 carbon atoms, for example, acetyl, propionyl, butyryl, etc., Preferably those having 2 to 4 carbon atoms. The lower alkylidene group means a straight-chain or branched-chain alkylidene group having from 1 to 6 carbon atoms, for example, rnethylidene, ethylidene, isopropylidene, etc., preferably those having from 1 to 4 carbon atoms. carbon. Throughout the description and the present claims, the β-D-glucopyranosyl group has the following structure: EXAMPLES The present invention is illustrated by the following Examples and Reference Examples, but it should not be interpreted to be limited thereto.

EXAMPLE 1 - 5 2 '- (2, 3, 4, 6-Tetra-O-acetyl-β-D-gl-copyranosyloxy) -6'-hydroxy-4'-rnetylacetophenone (120 g) is dissolved in a cooled mixture of ethanol (1.2 liters) and a 50% aqueous solution of potassium hydroxide (240 g) and the same is added to the 5-forrnilbenzoCb] furan (42.4 g), and the mixture is stirred at At room temperature overnight under an argon atmosphere, the reaction solution was added with 4-direthylarninopyridine (29.5 g) and charcoal with 10% platinum (23.58 g) and the mixture was stirred at room temperature for 4.5 hours under atmospheric pressure. of hydrogen gas. The catalyst is separated- Filtration is carried out and the filtrate is washed with toluene and acidified with 18% hydrochloric acid under ice cooling. The mixture is extracted with ethyl acetate and the organic layer is washed successively with water, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. The washed aqueous layer is extracted with ethyl acetate and the organic layers are combined, dried and concentrated under reduced pressure. The residue is crystallized from water-ethanol to give 3- (5-benzoCb) furanyl) -2 '- (β-D-glucopyranosyloxy) -6'-hydroxy-1-rnethylpropiophenone (82.4 g). p.f. 152.5-154 ° C ESI-MS (rn / z): 476 (M + NH4) +] IR (nujol, crn-l): 3560, 3510, 3350, 3270, 1630 NMR (DiSO-ds) or: 2.24 ( 3H, s), 3.00 (2H, t, 3 = 7.4, the unit of 3, the coupling constant, is Hz, thereafter, the same), 3.1-3.5 (7H, rn), 3.7K1H, ddd, 3 = 2.0, 5.5, 12), 4.59 (1H, t, 3 = 5.8), 4.98 (1H, d, 3 = 7.3), 5.05Í1H, d, 3 = 5.1), 5.12.1H, d, 3 = 4.6), 5.29 (1H, d, 3 = 5.1), 6.40 (1H, d, 3 = 0.4), 6.54Í1H, s), 6.88 (1H, dd, 3 = 0.9, 2.2), 7.22 (1H, dd , 3 = 1.8, 8.4), 7.46 (1H, d, 3 = 8.6), 7.53 (1H, d, 3 = 1.5), 7.93 (1H, d, 3 = 2.2), 11.90 (1H, s).

EXAMPLE 2 (1) Dissolve 3- (5-BenzoCb3furanyl) -2 '~ (β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone (2.50 g) in acetone (20 ml) and add to them Potassium carbonate (2.13 g) and allyl bromide (933 mg), and the mixture is refluxed for 6 hours. After cooling, the reaction mixture is poured into ice water and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (chloroform solvent / methanol) to give 3- (5-benzo bH furanyl) -2 '- (β-D-glucopyranosyloxy) -6'-allyloxy-4'-rhenylpropiophenone. (1.63 g). ESI-MS (rn / z): 521 C (M + Na) +], 516 C (M + NHA) +3 IR (net, cm-1): 3019, 1691, 1609 NMR (DMSO-de) or: 2.28 (3H, s), 2.92-3.02 (2H, rn), 3.04-3.32 (6H, n), 3.40-3.50 (1H, rn), 3.66-3.74 (1.H, rn), 4.50 (2H, dt , 3 = 1.5, 5.0), 4.57 (2H, t (br)), 4.87 (1H, d, 3 = 7.7), 5.03.1H, d, 3 = 4.8), 5.09 (1H, d (br)), 5.16 (1H, ddt, 3 = 10.4, - 5 1.7, 1.5), 5.23UH, br), 5.26 (1H, ddt, 3 = 17.4, 1.7, 1.5), 5.90 (1H, ddt, 3 = 1.7.4, 10.4, 5.0), 6.56.1H, s), 6.66 (1H, s), 6.88 (1H, dd, 3 = 0.9, 2.2), 7.18 (1H, dd, 3 = 1.7, 8.4), 7.45 (1H, d , 3 = 6.4), 7.49 (1H, d, 3 = 1.3), 7.93 (1H, d, 3 = 2.2). (2) Dissolve 3- (5-BenzoCb3 uranii) -2 '- (ß-D-10 glucopyranosyloxy) -6'-allyloxy-4'-rnetylpropiophenone (500 ng) in 2,4,6-collidine (5 l ) and the mixture is cooled to -40 ° C with dry ice-acetone, and to this is added dropwise a solution of methyl chloroformate (114 rng) in dichloromethane (0.5 rnl) with stirring. The mixture is stirred at -40 ° C for 1 hour and stirred at room temperature for 1.5 hours. The reaction mixture is poured into a cold 10% aqueous solution of citric acid and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The resulting residue is purified by silica gel -20 column chromatography (solvent: chloroform / methanol) to give 3- (5-benzoC-furanyl) -2 '- (6-0-r-methoxy-carbonyl-β-D-glycopyranosyl) - xi) -6 '-alyloxy-4' -rnethylpropiophenone (487 rng). ESI-MS (rn / z): 579 C (M + Na) +3 IR (net, crn-l): 3401, 1751, 1609 25 NMR (DMSO-de) or: 2.27 (3H, s), 2.92- 2.99 (2H, rn), 3. 02-3.32 (5H, m), 3.57-3.62 (1H, rn), 3.64 (3H, s), 4.13 (1H, dd, 3 = 6.3, .1.1.4), 4.38 (1H, dd, 3 = 1.7 , 11.4), 4.50 (2H, dt, 3 = 5.0, 1.5), 4.91 (1H, d, 3 = 7.7), 5.16 (1H, ddt, 3 = 1.0.6, 1.8, 1.5), 5.21 (1H, d , 3 = 5.0), 5.26 (1H, ddt, 3 = 17.4, 1.7, 1.6), 5.35 (2H, d, 3 = 5.7), 5.89 (1H, ddt, 3 = 17.2, 10.6, 4.9), - 5 6.57QH, s), 6.61 (1H, s), 6.87 (1H, dd, 3 = 0.9, 2.2), 7.16 (1H, dd, 3 = 1.8, 8.4), 7.45 (1H, d, 3 = 8.4 ), 7.47 (1H, s), 7.93 (1H, d, 3 = 2.0). (3) 3- (5-BenzoCb3furanyl) ~ 2 '- (6--0-r-methoxycarbonyl-β-D-gluco-isosiloxy) -6'-allyloxy-4'-methylpropiophenone is dissolved. (470 rnG) in acetonitrile (7 rnl) and therein dichlorobis (triphenylphosphine) -palladium (II) (17.7 rng) and ammonium formate (319 rng) are added, and the mixture is heated under reflux overnight. After cooling, the insoluble materials are separated by filtration and the filtrate is concentrated, fil Ethyl acetate and water are added to the residue, and the mixture is stirred. The organic layer is separated, washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography. (solvent: chloroform / methanol) to give 3- (5-benzoCb3 furanyl) -2 '- (6-0- - 20-methoxycarbonyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetylpropiophenone (370 mg) . ESI-MS (rn / z): 539 C (M + Na) +3, 534 C (M + NH4) +3 IR (nujol, cm-1): 3200-3500, 1714 NMR (DMSO-de)?: 2.23 (3H, s), 2.99 (2H, t, 3 = 7.4), 25 3.14-3.42 (5H, rn), 3.65 (3H, s), 3.63-3.69 (1H, rn), 4.16 (1H, dd, 3 = 6.6, 11.5), 4.39 (1H, dd, 3 = 2.0, 11.5 ), 5.02 (1H, d, 3 = 7.5), 5.25 (1H, d, 3 = 5.0), 5.37 (1H, d, 3 = 5.3), 5.39 (1H, d, 3 = 5.3), 6.42UH, s ), 6.50 (1H, s), 6.88 (1.H, dd, 3 = 0.9, 2.2), 7.20 (1H, dd, 3 = 1.7, 8.4), 7.47 (1H, d, 3 = 8.4), 7.51, (1H, d, 3 = 1.3), 7.93 (iH, d, 3 = 2.2), 11.80 (lH, s) EXAMPLES 3-9 (1) The corresponding starting compounds are treated in the same manner as in Example 2- (2) to give the compounds listed in Tables 1-4.

TABLE 1 TABLE 2 Ex. No Rl Physico-chemical properties ESI- - M (m / z): 602 [(M + NH4) +] IR (nefca, cm-i): 3400, 1743, 1698, 1609 KMN (DMSO-d6) d: 1.15 , 1.17 (3H coffee ates d, J = 6.5), 2.29 (3H, s), 2.93-2.99 (2H, m), 3.03-3.30 (5H, m), 3.60 (1H, ddd, 1 = 2.0, 7.0, 9.0), 4.10 (1H, dd, J = 7.0, 11.5), 4.35 (1H, dd, J = 2.0, 11.5), 4.50 - (l) (2H, dt, J = 5.0, 1.5), 4.70 (1H, heptet, J = 6.5), 4.91 OCO- (1H, d, J = 7.5), 5.16 (1H, ddt, J = 10.5 , 3.5, 1.5), 5.18 (1H, d, J = 5.5), 5.26 (1H, ddt, J = 17.5, 3.5, 1.5), 5.34 (2H, d, J = 5.5), 5.89 (1H, ddt, J = 17.0, 10.5, 5.0), 6.57 (1H, s), 6.63 (1H, s), 6.87 (1H, dd, J = 1.0, 2.0), 7.16 (1H, dd, J --- 1.5, 8.5), 7.45 (1H, d, J = 8.5), 7.47 (1H, d, J = 1.5), 7.93 (1H, d, J = 2.0) ESI-MS (m / z): 616 [(M + NH4) +] IR (nujol, cm-i): 3470, 3280, 1750, 1700 HMN (DMSO-d6) d: 0.84 (3H, t, J = 7.3), 1.27 (2H, m), 1.51 (2H, m), 2.28 (3H, s), 2.96 (2H, m), 3.0- 3.4 (5H, m), 3.60 (1H, m), 4.00 (2H, dt, J --- 1.0, 6.6), 4.11 (1H, dd, J = 6.7, 11.6), 4.37 (1H, dd, J = 1.7, 11.5), 4.50 (2H, dt, J = 4.9, 1.5), 4.91 (1H, d, 6- (D CH3 (CH2) 3OCO- J = 7.7), 5.16 (1H, ddt, J = 10.5, 1.7, 1.5), 5.20 (1H, d, J = 5.1), 5.25 (1H, ddt, J = 17.3 , 1.7, 1.7), 5.34 (1H, d, J = 5.3), 5.35 (1H, d, J = 5.7), 5.89 (1H, ddt, J = 17.4, 10.5, 5.5), 6.58 (1H, s), 6.63 (1H, s), 6.87 (1H, dd, J = 0.9, 2.2), 7.16 (1H, dd, J = 1.7, 8.4), 7.45 (1H, d, J = 8.5), 7.46 (1H, d, J = 2.0), 7.93 (1H, d, J = 2.2) CURD 3 TABLE 4 Ex. No. Rl Chemical and physical properties ESI-MS (m / z): 588 [(M + NH4) +] IR (tit, cm-i): 3409, 1755, 1699, 1609 EMM (DMSO-d6) d: 2.29 (3H, s), 2.94-3.00 (2H, m), 3.03-3.34 (5H, m), 3.23 (3H, s), 3.58-3.64 (1H, m), 3.93 (1H, d, J = 16.5 ), 4.01 (1H, d, J = 16.7), 4.12 (1H, dd, J = 6.9, 11.7), 4.40 (1H, dd, J = 1.8, 9- (D CH3OCH2CO- 11.7), 4.50 (2H, dt, J = 4.9, 1.5), 4.93 (1H, d, J = 7.5), 5.16 (1H, ddt, J = 10.6, 1.8, Í.5), 5.21 (1H, d, J = 5.5), 5.26 (1H, ddt, J = 17.4, 1.8, 1.7), 5.33 (2H, m), 5.89 (1H, ddt, J = 17.4, 10.6, 5.0), 6.58 ( 1H, s), 6.62 (1H, s), 6.87 (1H, dd, J = 0.9, 2.2), 7.17 (1H, dd, J --- 1.7, 8.4), 7.45 (1H, d, J --- 8.4), 7.48 (1H, d, J = 1.5), 7.93 (1H, d, J = 2.0) (2) The compounds listed in Tables 5-8 are obtained in the same manner as in Example 2- (3) TABLE 5 kl TABLE 6 40 TABLE 7 TABLE 8 EXAMPLE 10 3- (5-BenzoHb) furanyl) -2 '- (ß-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetylpropiofen.na (400 rng) is dissolved in trimethyl ortho-acetate (5 rnl) and pyridine p-toluenesulfonate (22 rng) is added thereto. and the mixture is stirred at room temperature for 1 hour. The reaction mixture is diluted with ethyl acetate and poured into a saturated solution of sodium hydrogen carbonate. The mixture is stirred and the organic layer is separated, washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: chloroform / methanol) to give 3- (5-benzo- [furanyl] -2 '- (4,6-0- (1-methoxy-1-idene) -β. -D-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone (320 mg). ESI-MS (rn / z): 357 C (M + Na) +], 515 C (M + H) +] IR (nujol, crn-l): 3423, 1631 NMR (DMSO-dβ) 6: 1.40 ( 3H, s), 2.25 (3H, s), 2.99 (2H, t, 3 = 7.5), 3.23 (3H, s), 3.26-3.82 (8H, rn), 5.18 (1H, d, -. = 7- 7), 5.38 (1H, d, 3 = 5.3), 5.16 (1H, d, 3 = 5.7), 6.41 (1H, s), 6.55 (1H, s), 6.84 (1H, dd, 3 = 0.9, 2.2 ), 7.19 (1H, dd, 3 = 1.7, 8.4), 7.47Í1H. d, 3 = 8.4), 7.51 (1H, d, 3 = 1.3), 7.94 (1H, d, 3 = 2.2), 11.7 (1H, s).

EXAMPLE 11 3- (5-BenzoCb) furanyl) -2 '- (ß-D-glucopypi-nosyloxy) -6'-hydroxy-4'-rnetylpropiophenone (1.87 mg) in dichloromethane (36 ml) is suspended and added thereto p-toluenesulfonic acid (78 rng) and benzaldehyde dimethylacetate at room temperature. The mixture is stirred at room temperature for 1.5 hour. The mixture is concentrated under reduced pressure and to the residue are added ethyl acetate and a saturated aqueous solution of sodium acid carbonate. The mixture is stirred and the organic layer is separated, it is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: chloroform / acetone) to give 3- (5-benzoCb) furanyl) ~ 2 '~ (4,6-0-benzylidene-β-D-gl-copyranosyloxy) ) -6 '-hydroxy-4'-rneti 1 own phenone na (2.03 g). ESI-MS (rn / z): 569 CM + Na) +3, 547 Ci + H) +] IR (net, cpr i): 3450, 1631 NMR (DMS0-U6-6: 2.09 (3H, s), 3.01 (2H, t, 3 = 7.4), 3.34-3.48 (4H, n), 3.58-3.70 (3H, rn), 4.23 (1H, rn), 5.22 (1H, d, 3 = 7.7), 5.51 (1H , d, 3 = 4"9), 5.59 (1H, s), 5.64 (1H, d, 3 = 5.5), 6.42 (1H, s), 6.59 (1H, s), 6.90 (1H, dd, 3 = 0.9, 2.2), 7. 22 (lH, dd, 3 = 1.8.8.4), 7.36-7.53 (7H, rn), 7.95 (1H, d, 3 = 2.2), 11.80 (lH, s). (2) In 10 rnl of N, N-dirnethylformamide was dissolved 1. 00 g of 3- (5-benzoCb) furanyl) -2 '- (4,6-O-benzylidene-β-D-gl-copyranosyl-oxy) -6'-hydroxy-4'-rnetylpropiophenone and to this 747 are added mg of imidazole and 827 rng of t-butyl-dirnethyl chlorosilane. The mixture is stirred at room temperature for 13 hours, and poured into ice water. The mixture is extracted with ethyl acetate, and the organic layer is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent, hexane / ethyl acetate) to give 1.06 g of 3- (5-benzoC] furanyl) -2 '- (3-0- t-but i dirnet). lysilyl-4, 5-0-benzyl i den-ß-D-glucopypi loxy) -6'-butyl-dirnetylsilyloxy-4'-rnethyl-propiophenone. FOB-MS (rn / z): 797 C (M + Na) +3 Rl (nujol, crn-l): 3459, 1691, 1610 RMM (DMSO-dβ) 6: 0.01 (3H, s), 0.08 (3H , s), 0.18 (6H, s) 0.86 (9H, s), 0.89 (9H, s), 2.28 (3H, s), 2.93-3.02 (2H, rn), 3.04-3.15 (2H, rn), 3.28 (1H, rn), 3.44 (1H, rn), 3.62 (2H, rn), - 5 3.74 (1H, t, 3 = 8.8), 4.18 (1H, rn), 4.18 (1H, rn), 5.18 (1H , t, 3 = 7.9), 5.56 (1H, d, 3 = 7.0), 5.58 (1H, s), 6.40 (1H, s), 6.71 (1H, s), 6.88 (1H, dd, 3 = 0.9, 2.2), 7.17 (1H, dd, 3 = 1.8, 8.6), 7.36-7.49 (7H, rn), 7.93 (1H, d, 3 = 2.2) (3) In 5.4 i of pyridine were dissolved 1.Q4 g of 3-10 (5-benzo L bl-franil) -2 '- (3-0-t-butyldirnethylsilyl-4,6-0-benzylidene-β-D-glucopyranosyloxy) - 6'-butyldirnethylsilyloxy-1-rnethylpropiophenone and this added 2.7 nmol of acetic anhydride. The mixture is stirred at room temperature overnight and poured into an iced aqueous solution of acid citrus to 10%. The mixture is extracted with ethyl acetate and the organic layer is washed with water and a saturated aqueous solution of sodium hydrogen carbonate, dried and concentrated under reduced pressure to give 1.09 g of 3- (5-benzoCb3furanyl) -2 '- (2-0-acetyl-3--0-t-butyldimethylsilyl-4, 6-0-benzylidene-β-D-gluco - 20 p-ranosyl i) -6'-t-butyldimethylsilyloxy-4'-methylpropiophenone. ESI-MS (rn / z): 840 H (M + Na) +] Rl (net, crn-l): 1753, 1705, 1609 NMR (DMS0-d6) 6: -0.04 (3H, s), 0.00 ( 3H, s), 0.17 (3H, s), 0.17 (3H, s), 0.78 (9H, s), 086 (9H, s). 2.02 (3H, s), 2.28 (3H, 8), 2.80-3.02 (4H, n), 3.62 (1H, t, 3 = 9.0), 3.70-3.85 (2H, n), 4.04, (1H, t, 3 = 9.2), 4.29 (1H, dd, 3 = 3.7, 8.8), 4.93 (1H, t, 3 = 9.0), 5.38 (1H, d, J = 8.1), 5.65 (1H, s), 6.42 (1H, s), 6.65 (1H, s), 6.90 (1H, dd, 3 = 0.9, 2.2), 7.15 (1H, dd, 3 = 1.8, 8.6), 7.37-7.47 (6H, m), 7.50 (1H, d, 3 = 8.6), 7.94 (1H, d, 3 = 2.2) (4) In a mixture of 23 rnl of tetrahydrofuran and - 5 2.3 rnl of acid acetic, 1.07 g of 3-Í5-benzoCb] furanyl) -2 '- (2-O-acetyl-3-0-t-butydirnethylsilyl-4,6-benzylidene-β-D-glucopyranosyloxy) -6' were dissolved. -butyldirnethylsilyloxy-1-rnethylpropiophenone and then 685 ng of tetra-n-butylaronium fluoride were added and the mixture was stirred at room temperature for 25 minutes. The reaction mixture is concentrated and the residue is dissolved in ethyl acetate and poured into ice water. The organic layer is washed with water, dried and concentrated under reduced pressure to give 968 rng of 3- (5- benzoCb-1 furanyl) -2 '- (2-0-acetyl-3-Ot-butydirnethylsilyl-4, 6-0- 15 benzylidene-β-D-glucopyranosyl-oxy) -6'-hydroxy-4'-inethylpropylthiane. FRB-MS (rn / z): 725 C (M + Na) +] Rl (net, crn-l): 1753, 1634 NMR (DMSO-de) 6: -0.05 (3H, s), 0.00 (3H, s), 0.78 - 20 (9H, s) 2.03 (3H, s), 2.24 (3H, s), 2.92-2.99 (2H, rn), 3.05-3.11 (2H, rn), 3.60 (1H, t, 3 = 9.1) 3.72 (1H, t, 3 = 9.3) 3.77-3.85 (1H, rn), 4.04 (1H, rn), 4.27 (1H, dd, 3 = .2, 9.2), 4.95 (1H, t, 3 = 8.5) 5.46 (1H, d, = 8.1), 5.64 (1H, s), 6.42 (1H, s), 6.52 (1H, s), 6.89 (1H , dd, 3 = 0.9, 2.2), 7.20 (1H, dd, = 1.7, 8.3), 7.36-7.46 25 (5H, rn), 7.50 (1H, d, 3 = 8.3), 7.51 (1H, rn), 7.94 (1H, d, 3 = 2.2), . 7 (1H, s) (5) In 35 rnl of acid acot co 958 rng of 3 - (5-benzo C b 3 f? Ram 1) - 2 '- (2 -0-acet 1-3 - - t-buti dune t 1 li 1- 4, 6-0-benzyl den-ß-D-gluco-rans? Lox) -6 '-hydrox? -4' -rneti-propiophenone and to the mixture were added ki of water and 75 rng-5 of acid p-toluensul phonic and the mixture was stirred at room temperature for 4 days. The reaction mixture was poured into 700 nmol of ice water and the mixture was extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The residue is purified median, and column chromatography of silica gel (solvent; chloroform / methanol) to give 420 rng of 3- (5-benzoCb) furaml) -2 '- (2-0-acet-l-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetyl propiophenone . Mp 160 ° C GI (gradual melting) ESI-MS (rn / z): 518 C (M + NH4) + 1 15 Rl (nujol, crn-l): 3100-3510, 1752 NMR (DMSO-dd) 6: 1.99 (3H, s), 2.22 (3H, s), 2.90- 2.97 (2H, rn), 3.03-3.11 (2H, rn), 3.21-3.31 (1H, rn), 3.42-3.53 (3H, rn), 3.72 (1H, m), 4.67 (1H, t, 3 = 5.6), 4.78 (1H, dd, 3 = 8.2, 9.5), 5.20 (1H, d, 3 = 8.1), 5.28 (1H, d, 3 = 5.3), 5.36 (1H, - 20 d, 3 = 5.5), 6.39 (1H, s), 6.52 (1H, s), 6.88 (1H, dd, 3 = -0.9, 2.2), 7. 18 (1H, dd, 3 = 1.7, 8.4), 7.47 (1H, d, = 8.4), 7.50 (1H, d, 3 = 1.3), 7.93 (1H, d, 3 = 2.2), 10.86 (1H, s ).

EXAMPLE 12 (1) In 20 rnl of pyridine, 2.02 g of 3- (5-benzoCb] furanyl) -2 '- (4,6-0-benzylidene-β-D-glucopyranosyloxy) -6'-hydroxy were dissolved. -4 '-rnethylpropiophenone and 2.27 g of acetic anhydride are added to the mixture. The mixture is stirred at room temperature for 4.5 hours and poured into ice-cold aqueous acetic acid solution 10% and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure to give 2.37 g of 3 ~ (5-benzoCbpfuranyl) -2 '- (2,3-di-0-acetyl-4.6-0. -benzylidene-ß-D-glucopyranosyloxy) -6'-acetoxy-4'-rnetylpropiophenone. Mp 200-203 ° C ESI-MS (rn / z): 690 IKM + NH *) *] IR (nujol, crn-l): 1764,1747, 1699, 1619 NMR (DMSO-dβ) 6: 1.94 (3H , s), 2.01 (3H, s), 2.02 (3H, s), 2.34 (3H, s), 2.87-3.03 (4H, rn), 3.76 (1H, t, 3 = 9.9), 3.90 (1H, t , 3 = 9.4), 3.97 (1H, dd, 3 = 4.5, 9.9), 4.44 (1H, dd, 3 = 4.6, .10.0), 5.07 (1H, dd, 3 = 7.9, 8.1), 5.40 (1H, t, 3 = 9.4), 5.63 (1H, s), 5.68 (1H, d, 3 = 7.9), 6.74 (1H, s), 6.91 (1H, dd, = 0.9, 2.2), 7.00 (1H, s) , 7.17 (1H, dd, = 1.8, 8.6), 7.39 (5H, s), 7.49 (1H, d, 3 = 1.3), 7.51 (1H, d, 3 = 8.4), 7.95 (1H, d, 3 = 2.2). (2) In 60 rnl of acetic acid 2, 04 g of 3- (5-benzoCb) furanyl) -2 '- (2,3-di-0-acetyl-4,6-0-benzylidene-β) were suspended. -D-glucopyranosyloxy.) -6'-acetoxy-4 '-rnethylpropiophenone and to the mixture were added 6 nl of water and 58 rng of p-toluenesulfonic acid. The mixture is stirred at room temperature for 20 hours and poured into 800 ml of ice water. The mixture is allowed to stand for 1 hour and the precipitated insoluble resin material is separated by filtration and dissolved in ethyl acetate. The organic layer is washed with a saturated aqueous solution of sodium hydrogen carbonate, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solve it rof or rrno / rne ta or 1) to give 1.72 g of 3- (5-benzoCbll f? Ranil) -2 '- (2,3-di-O-). acetyl-β-D-glucopyranosyloxy) -6'-acetoxy-4'-rn eti 1 p ro pi ofenone. ESI-MS (rn / z): 602 C (M + Nt-U) +3 IR (nujol, crn-l): 3404,1751 NMR (DMSO-de) 6: 1.87 (3H, s), 2.00 (3H , s), 2.00 (2H, s), 2.31 (3H, s), 2.84-3.11 (4H, r), 3.48-3.57 (2H, rn), 3.64-3.77 (2H, rn), 4.77 (1H, t , 3 = 5.8), 4.89 (1H, dd, = 8.1, 9.7), 5.10 (1H, t, 3 = 9.7), 5.50 (1H, d, 3 = 8.1), 5.59 (1H, d, 3 = 5.7) , 6.70 (1H, s), 5.89 (1H, dd, 3 = 0.9, 2.2), 7.00 (1H, s), 7.16 (1H, dd, 3 = 1.5, 8.5), 7.47-7.50 (2H, rn), 7.94 (1H, d, 3 = 2.2) EXAMPLE 13 (1) In a mixture of 5 rnl of tetrahydrofuran, 5 rnl of rnetanol and 0.1 rnl of water, 671 rng of 3- (5-benzoCb3furanyl) -2 '- (2,3-di-O-acetyl-4,6 were dissolved. -O-benzylidene-β-D-glucopyranosyloxy) -6'-acetoxy-4 '-rnethylpropiophenone and 419 grams of sodium hydrogencarbonate were added thereto. The mixture is stirred at room temperature for 30 hours and poured into water. The mixture is extracted with ethyl acetate and the organic layer is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent, hexane / ethyl acetate) -5 to give 410 rng of 3 ~ (5-benzoCb3 furanyl) ~ 2 '- (2,3-di-O-acetyl) 4, 5-0-benzylidene-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone. Mp 187 ~ 189 ° C ESI-MS (m / z): 648 C (M + NH 4) + 3 10 IR (net, crn-1): 1754.1633 NMR (DMSO-de) d: 1.97 (3H, s ), 2.01 (3H, s), 2.25 (3H, s), 2.90-2.98 (2H, rn), 3.01-3.09 (2H, rn), 3.76 (1H, t, 3 = 9.9), 3.88 (1H, t , 3 = 9.4), 3.95 (1H, dd, 3 = 4.6, 9.5), 4.32 (1H, dd, 3 = 4.6, 10.1), 5.05 (1H, dd, 3 = 7.9, 9.3), 5.40 (1H, 15 t, 3 = 9.3), 5.63 (1H, s), 5.63 (1H, d, 3 = 7.9), 6.43 (1H, s), 6.53 (1H, s), 6.90 ((1H, dd, 3 = 0.9- 7.95 (1H, d, 3 = 2.2), 10.70 (1H, s) (2) In 14 rnl of acetic acid, 395 rng of 3- (5-benzoCb3 furanyl) -2 '- (2.3 di-O) are dissolved. -acetyl-4,6-O-benzylidene-β-D-20-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone and to this were added 1.4 ml of water and 1.2 g of p-toluenesulfonic acid. It is stirred at room temperature for 2 days, poured into ice-water and left to stand for 1 hour.The colorless precipitate is collected by filtration and dissolved in ethyl acetate.The mixture is washed with water, dried and concentrated by evaporation. reduced pressure for Remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform / methanol) to give 297 rng of 3- (5 ~ benzoCb3 furanyl) -2 '- (2,3-di-0-acetyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone. Mp 151 ~ 153 ° C ESI-MS (rn / z): 550 [(+ h + l IR (nolol, crn-l): 3543.3288,1751,1729 NMR (DMSO-de) d: 1.91 ( 3H, s), 1.99 (3H, s), 2.23 (3H, s), 2.89-2.96 (2H, rn), 3.02-3.09 (2H, rn), 3.46-3.80 (4H, rn), 4.75 (1H, t, 3 = 5.7), 4.88 (1H, dd, 3 = 8.0, 9.8), 5.09 (1H, t, 3 = 9.4), 5.43 (1H, d, 3 = 8.0), 5.58 (1H, d, 3 = 5.7), 6.41 (1H, s), 6.54 (1H, s), 6.88 (1H, dd, 3 = 0.9, 2.2), 7.17 (1H, dd, 3 = 1.8, 8.4), 7.47 (1H, d, 3 = 8.9), 7.49 (1H, s), 7.94 (1H, d, 3 = 2.2), 10.48 (1H, s).

EXAMPLE 14 (1) In 4 rnl of N, N-direthylacetarnide 600 rng of 3- (5-benzoCb3 furanyl) -2 '- (4,6-O-benzylidene-β-D-glucopyranosyloxy) -6'-hydroxy- is dissolved. 4 '-rnetoxipropiophenone and to this 123 rng of triethylanine was added. To the mixture is added dropwise a solution of 115 rng methyl chlorofornate in 2 rnl of N, N-dirnetylacetamide under freezing over a period of 40 minutes. The mixture is stirred at the same temperature for 10 minutes and poured into ice-cold aqueous solution of 10% citric acid and extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent, chloroform / methanol) to give 637 mg of 3- (5-benzoCb3 furan.il) -2 '- (4,6-0-benzylidene-β-D) -glucopi ranosiloxy) -6'-nitroxycarbonyloxy-4 '-rnethylpropiophenone. ESI-MS (rn / z): 622 C (M + NH «) + 3 IR (nujol, cm-l): 3383,1762,1689,1618 NMR (DMSO-de) or: 2.34 (3H, s), 2.92-2.98 (2H, m), 3.05-3.25 (2H, rn), 3.33-3.47 (2H, rn), 3.54-3.70 (3H, n), 3.75 (3H, s), 4.22 (1H, rn), 5.28 (1H, d, 3 = 7.9), 5.51 (1H, d, 3 = 5.3), 5.57 (1H, s), 5.58 (1H, d, 3 = 5.9), 6.81 (1H, s), 6.91 (1H , dd, 3 = 0.9, 2.2), 7.09 (1H, s), 7.19 (1H, dd, 3 = 1.7, 8.6), 7.37-7.48 (5H, m), 7.50 (1H, d, 3 = 8.6), 7.50 (1H, d, 3 = 1.7), 7.95 (1H, d, 3 = 2.2) (2) In 60 ml of acetic acid, 618 mg of 3- (5-benzoC t> 3 furanyl) -2 '- (4,6-O-benzylidene-β-D-gl? Cop i. Ranosyl-oxy) -6'-nitroxy-rhyloxyloxy-4-methyl ? ropio fenona and to this 1 are added. 4 rnl of water and 19 rng of p-toluene phonic acid and the mixture is stirred at room temperature overnight. The reaction mixture is poured into ice water and extracted with ethyl acetate. The organic layer is washed with a saturated aqueous solution of sodium hydrogen carbonate, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent, chloroform / methanol) to give 428 rng of 3- (5 ~ benzoE b3 furanyl) -2 '- (.beta.-D-glucopyranosyloxy) -6' - rnetoxicarboniloxi-4 '-rnetilpropio- RQ phenone ESI-MS (rn / z): 534 C (M + NH «) + 1 IR (net, crn-l): 3387.1765 NMR (DMSO-de) 6. 2.32 (3H, s), 2.90-2.98 ( 2H, rn), 3.09-3.50 (7H, rn), 3.67-3.74 (1H, rn), 3.74 (3H, s), 4.60 (1H, t, 3 = 5.7), 5.04 (1H, d, 3 = 7.5 ), 5.08 (1H, d, 3 = 5.3), 5.15 (1H, d, 3 = 4.9), 5.37 (1H, d, J 5.5), 6.78 (1H, rn), 6.88 (1H, dd, 3 = 0.9 , 2.2), 7.03 (1H, s), 7.19 (1H, dd, = 1.8, 8.4), 7.45 (1H, d, 3 = 8.4), 7.51 (1H, d, 3 = 1.3), 7.93 (1H, d , 3 = 2.2) EXAMPLE 15 (1) The corresponding starting compounds are treated in the same way as in Example 14- (1) to give 3- (5-benzoC b3 furanyl) -2 '- (4,6-0-benzylidene-β-D) - l? copí anosilox i) -6'-acetox? ~ < . '- ethylpropiophenone. ESI-MS (rn / z): 606 C (M + NH 4) + 3 IR (nolol, crn-i): 3367, 767, 1690, 1617 NMR (DMSO-de) d: 2.03 (3H, s) , 2.33 (3H, s), 2.92-3.00 (2H, in), 3.05-3.73 (7H, m), 4.17-4.27 (1H, rn), 5.26 (1H, d, 3 = 7.7), 5.50 (1H, d, 3 = 5.3), 5.58 (1H, s), 5.58 (1H, d, 3 = 5.9), 6.68 (lH, rn), 6.91 (1H, dd, 3 = 0.9. 2.2), 7.05 (1H, s), 7. 19 (1H, dd, 3 = 1.5, 8.6), 7.37-7.52 (7H, rn), 7.95 (ll-l, d, 3 = 2.2) (2) It is treated 3- (5-Benzo-Cbl furanyl) -2 '. (4, 6-0-benzyl den-ß-D-glucopyronosilox?) -6'-acetoxy-4'-rnetylpropio-phenone in the same manner as in Example 14-? 2) to give 3- ei (5-benzoCb3 furanyl) -2 '- (.beta.-D-glucopyranosyloxy) -6'-acetoxy-4'-rnet i. ESI-I1S (rn / z): 518 C (M + NH *) +] Rl (net, crn-l): 3393,1769,1691,1618,1198 - 5 NMR (DMSO-de) 6: 2.02 (3H , s), 2.30 (3H, s), 2.89- 3.02 (2H, n), 3.06-3.51 (7H, rn), 3.67-3.75 (1H, rn), 4.58 (1H, t, 3 = 5.7), 5.02 (1H, d, 3 = 7.3), 5.05 (1H, d, = 5.1), 5.12 (1H, d, 3 = 4.8), 5.34 (1H, d, 3 = 5.5), 6.64 (1H, s), 6.88 (1H, dd, 3 = 0.9, 2. 2), 6.99 (1H, s), 7.19 (1H, dd, J = 1.7, 8.4), 7.47 (1H, 10 d, 3 = 8.4), 7.51 (1H, d, 3 = 1.3), 7.93, (1H , d, 3 = 2.0) EXAMPLE 16 In 3.5 rnl of N, N-dirnetilacetarnida 500 rng are dissolved15 of 3- (5-benzoCb3 furanyl) -2 '- (β-D-glucopyranosyl i) -6' -hydroxy-4'-rnethylpropiophenone and to this 315 mg of triethylanine are added. The mixture is dripped 282 mg of acetyl chloride under freezing and the mixture is stirred under freezing for 30 minutes and stirred at room temperature. '20 atmosphere during the night. The reaction mixture is poured into an ice-cold aqueous solution of 10% citric acid and extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform / methanol) to give 304 rng of 3- (5-benzoCb] furanyl) -2 '- (6-0-acetyl-β-D-glucopyranosyloxy) -5'-acetoxy-4'-rnethylpropionic phenone. ESI-MS (rn / z): 560 C (M + NH?) + 3 IR (net, crn-l): 3417.1769.1770, 1695.1618 NMR (DMSO-de) d: 1.97 (3H, s ), 2.02 (3H, s), 2.31 - 5 (3H, s), 2.88-2.98 (2H, rn), 3.04-3.32 (51-1, rn), 3.62-3.70 (1H, rn), 4.03 (1H , dd, 3 = 7.2, 1.4.1), 4.35 (1H, dd, 3 = 1.8, 11.7), 5.04 (1H, d, 3 = 7.5), 5.25 (1H, d, = 4.9), 5.34 (1H, d, 3 = 5.3), 5.44 (1H, d, 3 = 5.5), 6.67 (1H, s), 5.88 (1H, dd, 3 = 0.9, 2.2), 6.95 (1H, s), 7.18 (1H, dd , 3 = 1.8, 8.4), 7.47 (1H, d, 3 = 8.4), 7.50 10 (1H, d, 3 = 1.5), 7.94 (1H, d, 3 = 2.2) EXAMPLE 17 (1) In 33 rnl of 2, 4, 6-collidine 3.0 g of 3- (5-benzoCb furanyl) -2 '- (β-D-glucopyranosyloxy) -6'-hydroxy-4'-methylpropiophenone. The mixture is cooled to -40 ° C with dry ice-cold acetone and a solution of 1.71 g of 4-nitrophenyl chloroformate in 8.6 ml of dichloromethane is added dropwise with stirring. The mixture is stirred at -40 ° C for 1.5 hours and stirred at room temperature for 1 hour, and further it is stirred at 53 ° C for 3 hours. After cooling, the reaction mixture is poured into ice-cold 10% hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated at reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform / acetone) to give 2.16 g of 3- (5-benzoCb3 furanyl) -2 '- (4,6-0-carbonyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetyl propiophenone. FflB-MS (rn / z): 507 [(M + Na) +3, 485 C (M + H) +3-5 IR (nujol, crn-l): 3386.1753.1630 NMR (DMSO-de) 6: 2.25 (3H, s), 2.99 (1H, t, 3 = 7.4), 3.30-3.40 (3H, rn), 3.64 (1H, rn), 4.09-4.21 (2H, rn), 4.25 (1H, dd , J = 9.3, 9.7), 4.49 (1H, dd, 3 = 5.3, 3 = 9.2), 5.26 (1.H, d, 3 = 7.9), 5.80 (1H, d, 3 = 5.9), 5.86 (1H , d, 3 = 5.7), 6.43 (1H, s), 6.55 (1H, 10 s), 6.89 (1H, dd, 3 = 0.9, 2.2), 7.19 (1H, dd, 3 = 1.8, 8.6), 7.49 (1H, d, 3 = 8.6), 7.50 (1H, d, 3 = 1.9), 7.94 (1H, d, 3 = 2.2), 11.6 (1H, s). (2) In 40 rnl of methanol, 2.13 g of 3- (5-benzoCb] furanyl) -2 '- (4,6-O-carbonyl-β-D-glucopyranosyloxy) -6'-15 hydroxy-4' are dissolved. - methylpropiophenone and to this 84 rng of p-toluene phonic acid are added and the mixture is stirred at room temperature for 1 hour. The reaction mixture is diluted with ethyl acetate and poured into a saturated solution of sodium hydrogen carbonate. The mixture is stirred and the organic layer is separated, washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: chloroform / acetone) to give 986 rng of 3- (5-benzoCb3 furanyl) -2'- (4-0-rnetoxycarbonyl-β-D-glucopyranosyloxy) - 6'-hydroxy-4 / -rnethylpropiophenone. 25 ESI-MS (rn / z): 534 C (M + NH «) +3 IR (net, crn-l): 3459,1752,1631 NMR (DMSO-de) 6: 2.24 (3H, s), 3.00 (1H, t, 3 = 7.4), 3.32-3.45 (4H, rn), 3.49-3.60 (2H, m), 3.66-3.73 (1H, rn), 3.73 (3H, s), 4.54 (1H, t, 3 = 9.6), 4.82 (1H, t, 3 = 5.6), 5.12 (1H, d, 3 = 7.7), 5.52 (1H, d, 3 = 5.7), 5.60 (1H, d, 3 = 5.7), 6.44 (1H, - 5 d, 3 = 0.6), 6.56 (1H, d, 3 = 0.9), 6.90 (1H, dd, 3 = 0.9, 2.2), 7.22 (1H, dd, 3 = 1.7, 8.4), 7.47 (1H, d, 3 = 8.4), 7.54 (1H, d, 3 = 1.3), 7.93 (1H, d, 3 = 2.2), 11.8 (1H, s ).

EXAMPLE 18 10 a solution of 10 g of 3- (5-benzoCb) furanyl) -2'- (β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetylpropiophenone in 100 nrl of 2,4,5- collidine 10.31 g of methyl chloroformate are added dropwise at 0 ° C and the mixture is stirred at 0 ° C for 23 hours. The reaction mixture is stirred in ice cold 10% hydrochloric acid (300 rnl-300 rnl), and the mixture is extracted with 350 rnl of ethyl acetate. The organic layer is washed with water, a saturated aqueous solution of sodium carbonate and a saturated solution of sodium chloride, dried and concentrated under reduced pressure, The residue (11.96 g) is dissolved in 200 rnl of tetrahydrofuran. and to this is added 20 rnl of tert-butylarnine and the mixture is stirred at room temperature for 4 hours.The reaction mixture is poured into 10% ice cold hydrochloric acid (150 ml ~ 150 rnl) and extracted with 250 rnl acetate. ethyl.

The organic layer is washed with water, a saturated aqueous solution of sodium hydrogencarbonate and a saturated sodium chloride solution, dried and concentrated under reduced pressure. The residue is recrystallized 2 times from water-diethyl ether-diisopropyl ether to give 9. 14 g of 3- (5-benzot furanyl) -2 '- (6-0-r-methoxycarbonyloxy-β-D-glucopyol) 1 • 5 oxy) -6' -hydroxy-4 '-rnethylpropiophenone. P. f 78-82 ° C ESI-MS (m / z): 534 C (M + NH) +3 IR (nujol, crn-l): 3509.3401,3172,1733,1669,1632,1611 The NMR data (DMSO-de) are the same as those of the compound obtained in Example 2- (3).

EXAMPLE 19 In 30 rnl of ethylene glycol dirnethyl ether is dissolve 10 g of 3- (5-benzoCb furanyl) -2'- (β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropiophenone and to this is added 100 nrn of dirnethyl carbonate, 2 g of Novozirne 435 (manufactured by Novo Nordisk fi / S, Denmark) and 8 g of molecular sieve powder 4fi and the mixture is stirred at 40 ° C for 24 hours. hours, and the mixture is stirred at room temperature for 14 hours.The reaction mixture is diluted with chloroform and the insoluble materials are removed by filtration.The filtrate is concentrated to dryness and the residue is dissolved in ethyl acetate. wash successively with hydrochloric acid % aqueous, water, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of chloride. of sodium, dried and concentrated under reduced pressure. The residue is recrystallized 3 times from ether-isopropyl ether-water to give 7.9 g of 3- (5-benzoCb3 furanyl) -2 / - (6-0-rnetoxycarbonyl-β-D-glucopyranosyloxy) -6'-hydroxy -4 '-rnethylpropiophenone. The - 5 physicochemical properties of. compound are the same as those of the compound obtained in Example 18.

EXAMPLE 20 The corresponding starting compounds are treated in the same manner as in Example 1 to give 3- (5-benzo [b3 furanyl) -2 '- (β-D-glucopyranosyloxy) -6'-hydroxy-4'-ethyl - Propiophenone. P.f. 146-148.5 ° C 15 ESI-MS (rn / z): 490 H (M + Nh-4) + 3 IR (nujol, crn-l): 3600-3200,1633,1605 NMR (DMSO-de) d: 1.15 (3H, t, = 7.5), 2.55 (2H, q, 3 = 7.5), 3.00 (2H, t, J = 7.5), 3.10-3.50 (7H, rn), 3.58-3.74 (1H, m), 4.61 (1H, t, 3 = 5.5), 4.98 (1H, d, 3 = 7.5), 5.06 (1H, d, 3 = 5.5), -20 5.14 (1H, d, 3 = 5.0), 5.31 (1H, d, 3 = 5.5), 6.42 (1H, d, 3 = 1.5), 6.57 (1H, d, 3 = 1.5), 6.88 (1H, dd, 3 = 1.0, 2.0), 7.22 (1H, dd, 3 = 2.0, 8.5), 7.46 (1H, d, 3 = 8.5), 7.53 (1H, d, 3 = 2.0), 7.93 (1H, d, 3 = 2.0), 11.90 (1H, s).

EXAMPLE 21 In a mixture of 800 rnl of ice-cold ethanol and 200 g of a 50% aqueous solution of potassium hydroxide, 100 g of 2 '- (2, 3, k, fo-tetra, 0, acetl, β-) are dissolved. D-glucop anosi loxy) -6'-hydroxyl-4'-rnetiiacetophenone and to this 30.91 g of 5-forrnilbenzoC 3 furan are added. The mixture is stirred at room temperature overnight under an argon atmosphere. 400 nl of N, Nd? Rnet? Lacerated, 17.35 g of anhydrous p.phoram and 9.4 g of 10% palladium carbon (aqueous 51.4%) are added to the reaction mixture and the mixture is stirred at room temperature for 2 hours. hours under atmospheric pressure of hydrogen gas. The catalyst is removed by filtration, and the filtrate is washed with dusopropyl ether and acidified with 18% hydrochloric acid under freezing. The mixture is extracted with ethyl acetate and the organic layer is washed successively with water, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure. The residue is crystallized 2 times from water-acetone to give 66.86 g of colorless crystals, which are combined with 137.6 g of the compound prepared by the same procedure. The combined product (204.46 g) is recrystallized from water-ethanol to give 195.70 g of 3- (5 ~ benzoCb3furan?) ~ 2 '- (β-D-glucopyranosyl i) -5' ~ h? Drox? -4 '-met? l? rop? ofenona. The physicochemical properties of the compound are the same as those of the compound obtained in Example 1.

EXAMPLE 22 (1) The (300 rng) of 3- (5-benzoCb3 furanyl) -2 '- (β-D-glucopyranosyloxy) -6'-allyloxy-4'-rnetylpropiophenone obtained in Example 2 is dissolved in 3 ml of tetrahydrofuran, and to this are added under freezing 315 rng of 2, 4, 6-collidine, 486 mg of diphenyl chlorophosphate. The mixture is stirred at room temperature for 22 hours under an argon atmosphere. The reaction mixture is poured into ice-cold aqueous solution of 10% citric acid and extracted with ethyl acetate. The organic layer is successively washed with water, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent, chloroform / methanol) to give 327 mg of 3- (5-benzoCb3 furanyl) -2 '- (6-0-di-phenyl phosphono-β-D-glucopyranosyloxy). ) -5 '-alloyloxy-4'-methylpropiophenone. ESI-MS (rn / z): 748 C (M + NH 4) + 3 IR (nujol, crn-l): 3396, 1698, 1609 NMR (DMSO-de) d: 2.17 (3H, e), 2.95 ( 2H, t, 3 = 7.5), 3.0-3.3 (5H, rn), 3.72 (1H, d, 3 = 9.5, 2.5), 4.30 (1H, ddd, 3 = 5.5, 7.5, 11.5), 4.52 (2H, dt, 3 = 1.5, 5.0), 4.57 (1H, ddd, 3 = 3.5, 5.5, 11.5), 5.00 (1H, d, 3 = 7.5), 5.16 (1H, ddt, 3 = 11.0.3.5.1.5 ), 5.26 (1H, ddt, 3 = 17.5, 3.5.1.5), 5.3-5.4 (3H, br), 5.89 (1H, ddt, 3 = 17.5, 11.0, 5.0), 6.55 (lH, s), 6.68 ( 1H, s), 6.86 (1H, dd, 3 = 1.0, 2.0), 7.1-7.2 (7H, m), 7.30 (4H, dt, 3 = 8.0, 1.5), 7.44 (1H, d, 3 = 9.5) , 7.45 (1H, d, 3 = 2.0), 7.92 (1H, d, 3 = 2.0) "5 (2) The 308 rng of 3- (5-benzoyl! B 3 furanyl) -2'- (6-0 - di f eni 1 f or ph-ß-D-glucopyranosyloxy) -6'-allyloxy-4'-rnetyl? ropio phenone obtained in the previous one (1) are dissolved in 3 rnl of acetonitrile and to this 80 rng format is added of ammonium and 3 rng of dichlorobis (triphenylphosphine) palladium (II), and the mixture was reflux for 1.5 hours under argon atmosphere. The reaction mixture is cooled to room temperature, poured into ice water, and extracted with ethyl acetate. The organic layer is washed successively with water and a saturated aqueous solution of sodium chloride, dried and concentrated under pressure reduced. The residue is purified by silica gel column chromatography (solvent, chloroform / methanol) to give 246 rng of 3- (5-benzoCb3 furanyl) -2 '- (6-0-diphenylphosphono-β-D-glucopyranosyloxy) - 6'-Hydroxy-4'-methylpropiophenone. ESI-MS (m / z): 708 ü (M + NH4) + 3 * 20 IR (nujol, crn-l): 3405, 1630, 1600 NMR (DMSO-de) d: 2.13 (3H, s), 2.98 (2H, t, 3 = 7.0), 3.2-3.5 (5H, rn), 3.75-3.85 (lH, rn), 4.3-4.4 (1H, rn), 4.55 (1H, ddd, 3 = 3.5.5.5,11.5 ), 5.10 (1H, d, 3 = 1.0), 6.57 (1H, d, 3 = 5.0), 5.41 (1H, d, 3 = 4.5), 5.43 (1H, d, 3 = 5.5), 6.39 (1H, d, 3 = 1.0), 25 6.57 (lH, d, 3 = 1.0), 6.85 (1H, dd, 3 = 1.0, 2.0), 7.1-7.2 (7H, rn), 7. 29 (4H, dt, 3 = 8.0, 2.5), 7.44 (1H, d, 3 = 9.5), 7.49 (1H, d, 3 = 2"0), 7.92 (1H, d, 3 = 2.0), 11.84 ( lH, s) (3) In 33 rnl of 1,4-dioxane 764 rng of 3- (5-benzoCb3furan.il) -2 '~ (S-0-diphenylphosphono-β-D-glucopyranosyl siloxy) is dissolved. 6'-hydroxy-4'-methylpropiophenone and to this 33 j are added. 5 rnl of an aqueous 0.1N sodium hydroxide solution. The mixture is stirred at room temperature for 2.5 hours under an argon atmosphere. 50 mg of ammonium chloride is added to the reaction mixture and the mixture is concentrated under reduced pressure.

Ethanol is added to the residue and the insoluble materials are The residue is removed by filtration, filtered filtrate is added and the precipitates are collected by filtration and dried to give 327 g of 3- (5-benzo-buranyl) -2 '- (4, 6-0-) sodium. phosphinic - ß - D -glucopyranosyloxy) -6'-hydroxy-4'-rnethylpropionate. 15 ESI-MS (rn / z): 5.19 C (M + NHa) +3 IR (nujol, cin-l) p 3300, 1625, 1612 NMR (DMSO-de) d: 2.25 (3H, s), 2.97 ( 2H, t, 3 = 7"5), 3.3- 3.9 (8H, rn), 5.15 (1H, d, 3 = 7.5), 5.40 (1H, br), 5.55 (lH, br), 6. 41 (lH, s), 6.55 (lH, s), 6.98 (1H, dd, 3 = 1.0, 2.0), 7.19 »20 (lH, dd, 3 = 1.5, 8.5), 7.49 (1H, d, 3 = 8.5), 7.51 (1H, d, 3 = 1.5), 7. 92 (lH, d, 3 = 2.0) REFERENCE EXAMPLE 1 (1) In 50 rnl of pyridine, 50 g of orcinol rnonhydrate are dissolved and to this 133 rnl of acetic anhydride are added and the mixture is stirred at room temperature for 17 hours. The reaction mixture is concentrated under reduced pressure and the resulting residue is dissolved in 500 mL of ethyl acetate. The mixture is washed successively with 10% strength hydrochloric acid, water, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give * 74 g of orcinol. EI-MS (m / z): 208 (M +) 10 NMR (CDCl 3) d: 2.27 (6H, s), 2.35 (3H, s), 6.71 (1H, t, 3 = 1.8), (2H, rn) (2) Aluminum chloride (19.2 g) was heated at 90 ° C in chlorobenzene (50 ml), and a solution of orcinol diacetate (10 g) in chlorobenzene (8 ml) was added dropwise. for a period of 35 minutes. After the addition, the mixture is stirred at the same temperature for one hour and cooled. The reaction mixture is poured into ice-hydrochloric acid at 10% (100 rnl- 100 rnl) and the mixture is stirred for 30 minutes and extracted with ethyl acetate (100 rnl). The organic layer is washed with water, dried and concentrated under reduced pressure. Hexane (100 nl) is added to the residue, and the mixture is stirred at room temperature for 30 minutes. The precipitates are collected by filtration and dried to give 2 ', 6'-d? H? Drox? -4'-rnet? Lacetophenone (5.9 g), m.p. 146-148 ° C.

REFERENCE EXAMPLE 2 A mixture of 2 ', 6' -dihydroxy-4'-rnetylacetophenone (0.5 g), cadmium carbonate (2.08 g) and toluene (40 ml) are refluxed while the solvent is removed by means of a Dean-Stark trap. After 10 nl of the solvent are removed, the mixture is cooled to approximately SO ^ C and to this is added 2, 3, 4, 6-tetra-O-acetyl-0'-D-glucopyranosyl bromide (2"48). g) and the mixture is brought to reflux overnight. After cooling, the mixture is diluted with chloroform and the insoluble materials are removed by filtration. The filtrate is concentrated and the residue is crystallized from rnetanol to give 2 '- (2, 3,4, S-tetra-0 ~ acetyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetylacetophenone. (735 rng). P.f. 140-141.5 ° C ESI-MS (rn / z): 514 C (M + NH) +3 IR (nujol, crn-l): 175, 1725, 1650 NMR (DMSO-de) d: 1.96 (3H, s), 2.01 (9H, s), 2.26 (3H, f20 s), 2.39 (3H, s), 4.05-4.22 (2H, m), 4.28 (1.H, ddd, 3 = 2.5, 5.7, 9. 9), 5.00 (1H, dd, 3 = 9.5, 9.9), 5.10 (1H, dd, 3 = 8.0, 9.6), . 39 (1H, t, 3 = 9.5), 5.64 (1H, d, 3 = 8.1), 6.46 (1H, s), 6.48 (1H, s), 11.60 (1H, s) REFERENCE EXAMPLE 3 Potassium carbonate (414 g) is suspended in chloroform (1.3 1), and water (29 nl) is added thereto by gradually dripping. The mixture is added with tributylbenzilarnonium chloride (37 g), 2 ', 6' -dihydroxy-4'-rnetylacetophenone bromide (1.00 g), and 2, 3, 4, 6-tetra-0-acetyl-2 bromide. -D-gl? Copyranosyl (419 g), and the mixture is stirred at room temperature for 27 hours, water is added to the mixture (21 ml) and The mixture is stirred for an additional 2.5 hours. The mixture is neutralized with 18% hydrochloric acid (approximately 500 mmol) under cooling with ice, the mixture is added with 18% hydrochloric acid (approximately 200 ml) and water (500 ml), and the chloroform layer is separated, it is washed with water and a The aqueous solution is saturated with sodium chloride, dried and concentrated, the residue is added with rnetanol (400 ml), and the mixture is concentrated under reduced pressure to about half the volume of the same. The resulting filtrate is added with rnetanol (12 1), and the mixture is heated a little and stirred under cooling with ice ice for 30 minutes. The precipitates are collected by filtration and dried under reduced pressure to give 2'- (2,3,4,6-tetra-0-acetyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetylacetophenone (239.75 g). The physicochemical properties of the compound are the same as those of the compound obtained in the reference example 2.

REFERENCE EXAMPLE 4 (1) Suspend 3, 5-dirnetoxianilina (1.0 g) in a mixture of hydrochloric acid (3 rnl), acetic acid (2 rnl) and water * 5 (5 ml), to this a solution of sodium nitrite (473 mg) in water (5 ml) is added dropwise under cooling with ice over a period of 15 minutes. Ten minutes later, a solution of potassium iodide (1.62 g) in water (5 ml) is added to the mixture, and the mixture is heated to 80 ° C and stirred for one hour. The reaction mixture is extracted with diethyl ether and the extract is washed with water, dried and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: hexane / ethyl acetate), and recrystallized from acetate ethyl / hexane to give 3,5-dirnetoxyiobenzene (1.05 g), m.p. 73-74 ° C. (2) 3,5-Dirnetoxyiodobenzene (1.19 g) is dissolved in acetic acid (10 rnl), and to this 47% brornhydric acid (10 nl) is added at room temperature and the mixture is brought to reflux for 15 hours. The reaction mixture is cooled to room temperature and concentrated to dryness under reduced pressure. The residue is dissolved in ethyl acetate and the organic layer is washed with water, dried and concentrated under reduced pressure to give 3,5-dihydroxyiodobenzene (1.06 g). 25 EI-MS (m / z): 236 (M +) IR (pure, crn-1): 3325, 1605 NMR (CDCl 3) d: 5.22 (2H, s), 6.31 (1H, t, 3 = 2.5), 6.79 (2H, d, J = 2.5) (3) 3,5-Dihydroxyiodobenzene (1.02 g) is dissolved in pyridine (2.8 rnl), and acetic anhydride (1.53 g) is added to room temperature. The mixture is stirred for one hour and the reaction mixture is poured into an aqueous solution of 10% citric acid and extracted with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure to give 3,5-diacetoxyiodobenzene (1.37 g). 10 EI-MS (rn / Z): 320 (M +) 2.78,236 IR (pure, crn-l): 1771, 1586 NMR (CDCl 3) 6: 2.28 (6H. S), 6.92 (1H, t, 3 = 2.0), 7.36 (2H, d, 3 = 2.0) (4) 3, 5-Diacetoxyiodobenzene (860 rng) is dissolved in 15 1,4-dioxane (4 rnl), and tributyl tin vinyl is added (1.41 g) and dichlorobis (triphenylphosphino) αlyladl) (20 rng) at room temperature. The mixture is refluxed for 3 hours and cooled to room temperature. The mixture - * dilute with ethyl acetate and add an aqueous solution of 10% potassium fluoride. The mixture is stirred at room temperature for 30 minutes and the insoluble materials are removed by filtration. The filtrate is extracted with ethyl acetate and the organic layer is washed with water, dried and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography to give 3,5-diacetoxystyrene (585 rng).

EI-MS (rn / z): 220 (M +), 178.136 IR (pure, crn-l): 1771, 1610 NMR (CDCI3) d: 2.29 (5H, s), 5.32 UH, d, 3 = 11.0), 5.74 (1H, d, 3 = 17.0), 6.65 (1H, dd, 3 = 11.0, 17.0), 6.82 (1H, t, 3 = 2.0), 7.03 (2H, d, 3 = 2.0) (5) 3, 5-Diacetoxystyrene (580 rng) is dissolved in a mixture of ethyl acetate (6 rnl) and ethanol (2 rnl), and the mixture is subjected to catalytic reduction using 10% palladium-carbon (51.4% aqueous, 50 rng) under atmospheric pressure. Two hours later, the catalyst is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: hexane / ethyl acetate) to give 1,3-diacetoxy-5-ethylbenzene (450 mg) EI-MS (m / z): 222 (M +) IR (pure, crn-l): 1771, 1616 NMR (CDCI3) d: 1.23 (3H, t, 3 = 7.5), 2.28 (6H, s), 2.66 (2H, q, 3 = 7.5), 6.74 (1H, t, 3 = 2.0), 6.82 (2H, d, 3 = 2.0) (6) 1, 3-Diacetoxy-5-ethylbenzene is treated in the same way as in reference example l- (2) to give 2 ' , 6 '~ dihydroxy-4'-ethylacetophenone, mp 121-123 ° C. (7) 2 ', 6'-Dihydroxy-4'-ethylacetophenone is treated in the same way as in Reference Example 3 to give 2' - (2,3,4,6-tetra-0-acetyl-β- D-glucopyranosyloxy) -6'-hydroxy-4'-ethylacetophenone, mp 125-127 ° C.

REFERENCE EXAMPLE 5 (1) Zinc powder (purity: 85%, 14.75 g) is suspended in N, N-dimethylformamide (50 nmol) under an argon atmosphere and acetyl chloride (1.06 g) is added dropwise with stirring at 50 ° C. a period of 10 minutes and then the mixture is stirred for 15 minutes, the mixture is added dropwise a solution of 3,5-dimethoxybenzaldehyde (10 g) in dibromo methane (15.69 g) over a period of 20 minutes and mixing Stir for 30 minutes. The reaction solution is cooled with ice and a saturated aqueous solution of ammonium chloride (40 nmol) is added dropwise and then diethyl ether is added. The insoluble materials are removed by filtration and the filtrate is extracted with diethyl ether. The extract is washed successively with 10% hydrochloric acid, water, 10% aqueous sodium hydroxide solution and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give 3,5-dirnetoxystyrene (8.29). g) EI-MS (rn / z): 164 (M +), 149, 135, 121 IR (pure, crn-l): 1620, 1595 NMR (CDC13) d: 3.80 (6H, s), 5.25 (1H, dd, 3 = 1.0, 11.0), . 72 (lH, dd, 3 = 1.0, 17.5), 6.39 (1H, t, 3 = 2.5), 6.57 (2H, d, 3 = 2.5), 6.64 (1H, dd, 3 = 1.1.0, 17.5) (2) Dissolve 3,5-dirnetoxysti reindeer (8.29 g) in a mixture of rnetanol (70 rnl) and acetate of ethyl (10 ml), and the mixture is subjected to catalytic hydrogenation using 10% palladium-carbon (51.4% aqueous, 1.2 g) under atmospheric pressure. One hour later, the catalyst is removed by filtration and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent: hexane / ethyl acetate) to give l, 3-dimethoxy-5-ethylbenzene (7.07 g) EI-MS (rn / z): 1.66 (M +), 151, 137 IR (pure, cm-i): 1607, 1596 NMR (CDCl 3) 6: 1.22 (3H, t, 3 = 7.5), 2.60 (2H, q, 3 = 7.5), 3. 78 (6H, s), 6.30 (1H, t, 3 = 2.5), 6.37 (2H, d, 3 = 2.5) (3) L, 3-dirnetoxy-5-ethylbenzene (7.69 g) is dissolved in acetic acid ( 80 nl) and 47% brornhydric acid is added with stirring to room temperature. The mixture is refluxed for three hours and the reaction mixture is cooled to room temperature. The mixture is concentrated to dryness under reduced pressure and the residue is dissolved in ethyl acetate. The organic layer is washed successively with water and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure. The residue is recrystallized from diisopropyl ether-hexane to give l, 3-trihydroxy-5-ethyl-benzene (5.94 g), m.p. 97-98 ° C. (4) 1,3-Dihydroxy-5-ethylbenzene (5.92 g) is dissolved in pyridine (32 rnl) and acetic anhydride (17.5 g) is added at room temperature with stirring. One hour later, the reaction mixture is poured into ice-cold 10% hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is successively washed with water, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried and concentrated under reduced pressure to give 1-, 3- diacetox-5-et? -benzene (9.60 g), The physicochemical properties are the same as those of the compound obtained in reference example 4- (5).

EFFECTS OF THE INVENTION The compounds (3) of the present invention and a pharmaceutically acceptable salt thereof show an excellent hi-polyglic activity due to the increased effect of glucose excretion in the urine, based on the inhibition activity of glucose reabsorption renal tubular For example, when administered orally to rats, the present compounds increase the amount of glucose in the urine 50 times more than the fl ow. fidernás, the compounds (I) of the present invention, show low toxicity. In addition, the aglycone of the compounds (I), the hydrolyzate thereof, shows an extremely weak inhibitory activity against the glucose transporter of the facilitated diffusion type. Thus, the compounds (I) of the present invention can treat hyperglycemia, by which the cycle of autoexacerbation of glucose toxicity is interrupted, whereby the compounds (I) are useful in the prophylaxis or treatment of diabetes Cv.gr., diabetes rnelitus such as insulin-dependent diabetes (type I diabetes), insulin-independent diabetes (type 11 diabetes) 3, or in the rectification of hyperglyceria after food.

Claims (21)

NOVELTY OF THE INVENTION CLAIMS

1. - A propiophenone derivative of the formula (I) wherein OX is a hydroxy group which may be optionally protected, Y is a lower alkyl group and Z is a β-D-glucopyranosyl group in which one or more hydroxy groups may be optionally protected or a pharmaceutically acceptable salt of the same.

2. The compound according to claim 1, wherein Z is (i) a β-D-glucopyranosyl group in which one or more hydroxy groups may be acylated optionally, (ii) a β-D-glucopyranosyl group wherein two hydroxy groups combine to form a lower 1-lower alkyldidenedioxy group, a benzylidenedioxy group, a phosphinic dioxy group or a carbonyldioxy group together with the protecting groups thereof, or (iii) a β-D group -glucopyranosyl in which one or two hydroxy groups are acylated and two hydroxy groups combine to form a lower alkoxy-lower alkoxydenedioxy group, a benzylidenedioxy group, a phosph mcod ox group or a carbonyldioxy group together with the protecting groups of the misinos.

3. - The compound in accordance with the claim 2, wherein Z is a β-D-glucopyranosyl group in which one or more hydroxy groups may be optionally acylated by a group selected from a lower alkanoyl group, a lower alkoxy group, or carbonyl, a lower alkoxy-lower alkanoyl group and a lower alkoxy-lower alkoxycarbonyl group, or a β-D-glucopyranosyl group in which two hydroxy groups combine to form a lower 1-lower alkoxy-loweridendioxy group or a group phosphinic dioxy together with the protective groups of the same.

4. - The compound in accordance with the claim 3, wherein Z is a ß-D-glucopyranosyl group in which the 2-hydro group or the 2- and 3-hydroxy groups or the 4-hydroxy group, or the 6-hydroxy group can be acylated optionally by a group selected from a lower alkanoyl group, a lower alkoxycarbonyl group, a lower alkoxy- lower alkanoyl group and a n-alkoxy group; nferioi - lower alkoxycarbonyl, or a β-D-glucopyranosyl group in which the 4- and 6-hydroxy groups combine to form a lower alkoxy-lower alkylidendioxy group or a phosphinic-dioxy group together with the protecting groups thereof .

5. The compound according to claim 4, wherein OX is a hydroxy group, a lower alkanoyloxy group, or a cox i carboni lox i lower group, and Z is a β-D-glucopyranosyl group, a group 2-0- (lower alkanoyl) -β-D-glucopyranosyl, a 2, 3-di-0- (lower lcanoyl) -β-D-glucopyranosyl group, a 4-0- (lower alkoxycarbonyl) -β- group D-glucopyranosyl, a 6-0- (lower alkanoyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxycarbonyl) ~ .beta.-D-glucopyranosyl group,? N group 6-0- (lower alkoxy- lower alkanoyl) -β-D-glucopyranosyl, a 6-0 ~ (lower alkoxy-lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 4-6-0- (lower alkoxy-lower alkylidene) -β- group D-glucopyranosyl, or a 4,6-0-phosphinic-β-D-glucopyranosyl group.

6.- The compound in accordance with the claim 5, wherein 0X is a hydroxy group or a lower alkanoyloxy group, and Z is a β-D-glucopyranosyl group, a 2,3-di-0- (lower alkanoyl) -β-D-glucopyranosyl group, a group 4-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl, a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 4,6-0- (lower alkoxy-lower alkylidene) group ) -β-D-glucopyranosyl or a 4, 6-0-phosphino-β-D-glucopyranosyl group.

7. The compound in accordance with the claim 6, wherein 0X is a hydroxy group, Y is a methyl group or? N ethyl group, and Z is a β-D-glucopyranosyl group, a 4-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group, a 4,5-0- (lower alkoxy-lower alkylidene) -β-D-glucopyranosyl group or a group 4, 6-O-phosphinic-β-D-glucopyranosyl.

8. The compound according to claim 7, wherein Z is a ß-D-glucopyranosyl group or 6-0- (lower alkoxycarbonyl) -β-D-glucopyranosyl group.

9. 3- (5-BenzoCb3 furan.il) -2 '- (.beta.-D-glucopyranosyloxy) -6'-hydroxy-4'-rhenylpropiophenone or a pharmaceutically acceptable salt of the same.

10. 3- (5-Benzo-3-furanyl) -2 '- (6-0-rnetoxy-rbonyl-β-D-glucopyranosyloxy) -6'-hydroxy-4'-rnetyl-propiophenone or a pharmaceutically acceptable salt of the same.

11. A process for preparing a propiophenone derivative of the formula (I): wherein OX is a hydroxy group that can be optionally protected, Y is a lower alkyl group, and Z is a β-D-glucopyranosyl group in which one or more hydroxy groups may be optionally protected, or a pharmaceutically acceptable salt thereof, which comprises reducing a compound of the formula (II): wherein the symbols are the same as defined above, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt of the same.

12. A process for preparing a propiophenone derivative of the formul. (I-b): wherein R1 is an acyl group, OX is a hydroxy group which may be optionally protected, and Y is a lower alkyl group- or a pharmaceutically acceptable salt of the ism, which comprises acylating a compound of the formula (Ia): wherein the symbols are the same as defined above, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt of the same.

13. A process for preparing a propiophenone derivative of the formula (Ic): wherein R3 is an acyl group, OX is a hydroxy group that can be protected optionally, and Y is a lower alkyl group, or a pharmaceutically salt acceptable thereof, which comprises acylating a compound of the formula (Id) s wherein RUO and R2i0 are protected hydroxy groups, and the other symbols are the same as defined above, removing the protecting groups from the product, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt of the same.

14. A process for preparing a propiophenone derivative of the formula (Ie): wherein R * is an acyl group, OX is a hydroxy group that can be protected optionally, and Y is a lower alkyl group, or a pharmaceutically acceptable salt thereof, which 10 comprises acylating a compound of the formula (I-f): wherein UO, R210 and R310 are protected hydroxy groups, and the other symbols are the same as defined above, removing the protecting groups of the product, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt of the same. .

15. A process for preparing a propiophenone derivative of the formula (Ig): in which R2 is a lower alkyl group, OX is a hydroxy group that can be optionally protected, and Y is a lower alkyl group, or a salt pharmaceutically acceptable thereof, which comprises reacting a compound of the formula (Ih): wherein the symbols are the same as those defined above, with a compound of the formula (III): R20H (III) wherein R2 is the same as defined above, and if necessary, followed by the conversion of the product in a pharmaceutically acceptable salt thereof.

16. A process for preparing a propiophenone derivative of the formula (Ii): - wherein Rs is a hydrogen atom or a lower alkyl group and R6 is a lower alkoxy group, or R5 is a hydrogen atom and R6 is a lower alkyl group; is a phenyl group, or R5 and R6 can be combined 10 to form an oxo group, OX is a hydroxy group which may be optionally protected, and Y is a lower alkyl group, or a pharmaceutically acceptable salt of the same, which comprises reacting a compound of the formula (Ia): that defined above, with a compound of the formula (IV): RS Al \ / 25 C (IV) / \ RS A2 where fil and fl2 are starting groups, and the other symbols are the same as defined above, and if necessary, followed by the conversion of the product into a salt pharmaceutically acceptable thereof.

17. - A process for preparing a propiophenone derivative of the formula (I-j): wherein OXi is a protected hydroxy group, Y is a lower alkyl group, and Z is a β-D-glucopyranosyl group in which one or more hydroxy groups may be optionally protected, or a pharmaceutically acceptable salt of the same, which it comprises protecting the 6'-phenyl hydroxy group of a compound of the formula (Ik): wherein the symbols are the same as defined above, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt thereof.

18. A process for preparing a derivative of own enone of the formula (I-k) wherein Y is a lower alkyl group and Z is a β-D-glucopyranosyl group in which one or more hydroxy groups may be optionally protected, or a pharmaceutically acceptable salt 10 thereof, which comprises removing the protecting group of the compound of the formula (I-j): wherein OXi is a protected hydroxy group, and the other symbols are the same as defined above, and if necessary, followed by conversion of the product to a pharmaceutically acceptable salt of the same.

19. A process for preparing a compound of the formula (1-1): wherein OX is a hydroxy group that can be optionally protected, and Y is a lower alkyl group, or a pharmaceutically acceptable salt thereof, comprising subject to hydrolysis? n composed of the formula (I-rn): wherein R9 and Rio are the same or different and each protecting group for the hydroxy group, and the other symbols are the same as defined above, and if necessary, followed by the conversion of the product into a pharmaceutically acceptable salt of the same .

20. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1, mixed with a pharmaceutically acceptable carrier or diluent.

21. The use of a compound according to claim 1, in the production of a medicament for the prophylaxis or treatment of diabetes. •? I