CN1146534C - (4S,5S)-and (4R,5R)-gamma-methyl-delta-hydroxyl-alkanoic acid and its alkyl ester, preparation method and application - Google Patents
(4S,5S)-and (4R,5R)-gamma-methyl-delta-hydroxyl-alkanoic acid and its alkyl ester, preparation method and application Download PDFInfo
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- CN1146534C CN1146534C CNB011058803A CN01105880A CN1146534C CN 1146534 C CN1146534 C CN 1146534C CN B011058803 A CNB011058803 A CN B011058803A CN 01105880 A CN01105880 A CN 01105880A CN 1146534 C CN1146534 C CN 1146534C
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Abstract
The present invention relates to (4S, 5S)-and (4R, 5R)-gamma-methyl-delta-alkyl acid, alkyl ester compound thereof, a preparation method thereof and purposes thereof. The compound is obtained by that the asymmetrical evansaldol condensation is carried out for chiral propionyl compounds and aldehyde to obtain chiral alcoholic compounds, and hydroxy protection, reduction, oxidation, wittig reaction, hydrogenation and the removal of hydroxyl protecting group are carried out for the chiral alcoholic compound. The compound can be used for preparing spices and flavoring agents, such as optically active 4-methyl-5-alkyl-delta-valerolactone.
Description
The present invention relates to a kind of (4S, 5S)-and (4R, 5R)-γ-methyl-δ-alkyl acid and alkyl ester thereof, Preparation method and use.This compounds carries out asymmetric Evans aldol condensation by chirality propionyl compound and aldehyde, again through hydroxyl protection, reduction, oxidation, hydrogenation and get.This compound can be used for preparing the optically active 4-methyl of tool-5-alkyl-δ-Wu Neizhi.
Compound
And/or
R wherein
3Important chemical composition (the Kaiser of the delicate fragrance that to be orchid Aerngis confusa and Aerangis Kirkii during for n-pentyl give out at night, R.The scent of orchids:Olfactory and chemical investigations, Elsevier, Amsterdam, 1993.).Work as R
3Be C
3-C
8Can promote all during alkyl that many perfume and seasonings produce cananga oil (ylang-ylang), A Er in order to do this mountain herbal medicine (alpine herb) and creamy breath.4-methyl-5-alkyl-the δ-Wu Neizhi of racemization by 3-methyl-2-amyl group-ring penta-2-alkene-1-ketone through catalytic hydrogenation, Bayer-Villiger oxidation and get (Kaiser, R.Eur.Pat.Appl.EP513627 A1 19 Nov 1992.).Optically active 3 and 4 only have document to mention this two compound is synthesized (Masuzawa, Y.; Tamogami, S.; Kitahara, T.Nat.Prod.Lett.1999,13,239-246), but particular content is not seen any report as yet.
The purpose of this invention is to provide a kind of γ-methyl-δ-alkyl acid and alkyl ester thereof, its molecular formula is:
With
R wherein
1Be H or C
1-C
4Alkyl, R
2Be C
3-C
8Alkyl.
Another object of the present invention provides a kind of method for preparing above-claimed cpd.
The present invention also provides a kind of purposes of above-claimed cpd.
Method of the present invention is represented by following reaction expression:
R in the reaction formula
1Be H or C
1-C
4Alkyl, R
2Be C
3-C
8Alkyl is worked as R
3R during for hydrogen
4Be phenyl, sec.-propyl, benzyl; Work as R
4R during for hydrogen
3Be phenyl, sec.-propyl, benzyl; R
5Be benzyloxymethyl (BnOCH
2), methoxymethyl (MOM), pivaloyl group (Piv), the dimethyl tertiary butyl silica-based (TBS), ethanoyl (Ac), benzoyl (Bz), benzyl (Bn), X is Sauerstoffatom (O) or sulphur atom (S).Y=Cl, Br, AcO (work as R
5During=Ac).
Wu Yikang, people such as Shen Xin, the Tang Dynasty of army invented compound (R, S)-or (S; and synthetic method (CN 01105270.8) R)-7, compound (R, S)-or (S; R)-7 under organic solvent neutralization bases or acid effect, must compound 8 after with hydroxyl protection reagent newly-generated hydroxyl being protected.Described hydroxyl protection reagent is benzyloxy methyl chloride, methoxychlor methane, trimethylchlorosilane, dimethyl tertiary butyl chloride silane, Acetyl Chloride 98Min., Benzoyl chloride, pivaloyl chloride, chloroformic acid first (second) ester, aceticanhydride, benzyl chlorine (bromine), dihydropyrane, 2-methoxy propyl-2-alkene or vinyl ethyl ether.Described alkali is triethylamine, pyridine, diisopropyl ethyl amine, N, N-Tetramethyl Ethylene Diamine, 1,8-diazabicyclo [5.4.0] undecane-7-alkene (1,8-diazabicyclo[5.4.0]
Undec-7-ene is called for short DBU), sodium amide or sodium hydride etc.Described acid comprises the protonic acid or Louis (Lewis) acid of sulfuric acid, hydrochloric acid, tosic acid or boron trifluoride.The mol ratio of compound 7, hydroxyl protection reagent, alkali or acid is 1: 1～10: 0.01～1, and when adopting alkali, the mol ratio of compound 7 and alkali is with 1: 1～10 for well, compound 7 and sour mol ratio with 1: 0.01～1 for well.Temperature of reaction is-80 ℃～+ 40 ℃, and the reaction times is 0.1～40h; Described organic solvent is methylene dichloride, chloroform, pyridine, tetrahydrofuran (THF), methyl-sulphoxide, N, N '-dimethyl formamide (DMF), toluene or benzene etc.
Compound 8 is removed the chirality prothetic group with metal borohydride or the hydrogen reduction of aluminium lithium in organic solvent, get compound 9.The mol ratio of reactant and reductive agent is 1: 0.25～20.When-80 ℃～+ 40 ℃ temperature, reaction 0.1～40h.Described organic solvent is tetrahydrofuran (THF), methyl alcohol, ethanol, Virahol etc.Described metal borohydride is lithium boron hydrogen, sodium borohydride, potassium boron hydrogen, calcium boron hydrogen, zinc boron hydrogen.Solvent is a tetrahydrofuran (THF), methyl alcohol, ethanol, Virahol, the trimethyl carbinol.
Compound 9 is used Swern oxidation ((a) Omura, K. in organic solvent; Swern, D.Tetrahedron 1978,34,1655. (b) Mancuso, A.J.; Huang, S.-L.; Swern, D.J.Org.Chem.1978,43,2480.), PDT oxidation (Taber, D.F.; Amedio, J.C., Jr.; Jung, K.-Y.J.Org.Chem.1987,52,5621.), PDC (Corey, E.J.; Schmidt, G.Tetrahedron Lett.1979,399.) or PCC (Corey, E.J.; Suggs, J.W.Tetrahedron Lett.1975,2647.) oxidation etc. compound 10, temperature of reaction is-10 ℃～+ 80 ℃, the mol ratio of reactant and oxygenant is 1: 1～10.Reaction times is 0.1～24h.Above-mentioned oxygenant is oxalyl chloride-methyl-sulphoxide-triethylamine (Swern oxygenant), Vanadium Pentoxide in FLAKES-methyl-sulphoxide-triethylamine (PDT), pyridinium chlorochromate (PCC, pyridiumchlorochromate) or two chloro-chromic acid pyridines (PDC, pyridium dichlorochromate).
Compound 10 gets compound 11 with the Wittig reagent react in organic solvent.Reaction times is 0.1～48h.Temperature of reaction is-10 ℃～+ 80 ℃, and compound 12 is 1: 1～4 with the mol ratio of Wittig reagent.Described Wittig reagent molecule formula is
R wherein
1Be H or C
1-C
4Alkyl;
Compound 11 in organic solvent in the presence of catalyzer with the hydrogen effect, after removing hydroxyl protecting group, generate compound 1 or 2.
The hydrogenation temperature is-10 ℃～+ 50 ℃.The mol ratio of reactant and catalyzer is 1: 0.0001～1, and the reaction times is 0.1～24h.Catalyst system therefor is Ra-Ni (Lei Shi nickel) or Pd/C (palladium-carbon).Used hydrogen pressure is 0.1～3MPa.Obtain the saturated derivative of two keys of compound 11.As used protecting group R
5During for benzyl or benzyloxymethyl, remove hydroxyl protecting group and when the two key of hydrogenation, finish simultaneously, directly obtain compound 1 or 2 and need not other supplementary condition.As used protecting group R
5During for other protecting groups, also need remove protecting group again, get compound 1 or 2.
Removing the hydroxyl protecting group reaction conditions decides on used protecting group character.As mentioned above, as used protecting group R
5During for benzyl or benzyloxymethyl, remove hydroxyl protecting group and when the two key of hydrogenation, finish simultaneously, directly obtain compound 1 or 2 (R
1=C
1-C
4Alkyl) need not other supplementary condition; As used protecting group R
5Be the acetals protecting group, the examination base that uses when promptly protecting hydroxyl is during as benzyloxy methyl chloride, methoxychlor methane, dihydropyrane, 2-methoxy propyl-2-alkene or vinyl ethyl ether, above-mentioned pair of saturated derivative or the hydrogenation liquid of key is handled with the acid (aqueous solution) of 0.01～10N, gets compound 1 or 2; As used protecting group R
5For benzoyl, acetyl, pivaloyl, first or ethoxycarbonyl, front three is silica-based or dimethyl tertiary butyl when silica-based; hydrogenation liquid is with the solution-treated of water, methyl alcohol, ethanol or the tetrahydrofuran (THF) of the alkali of 0.01～10N; transfer to pH neutrality again; obtain removing the compound 1 or 2 that hydroxyl protecting group and ester group are hydrolyzed, wherein R
1=H.Described acid is acetic acid, sulfuric acid, hydrochloric acid, tosic acid etc.Described alkali is the hydroxide carbonate or first (second) oxycompound of basic metal or alkaline-earth metal.The temperature of reaction of removing hydroxyl protecting group is 20 ℃～60 ℃, and the reaction times is 1～48h.The consumption of acid or alkali is the solution/molar reactive thing of above-mentioned acid of 0.1～10ml or alkali.
Above-mentioned reaction is all carried out in organic solvent, and described organic solvent can be a methylene dichloride, chloroform, tetrahydrofuran (THF), methyl alcohol, ethanol, Virahol, the trimethyl carbinol, chloroform, vinyl acetic monomer, methyl-sulphoxide (DMSO) or N, N '-dimethyl formamide etc.Hydroxyl protection reaction and oxidizing reaction recommend to use solvent to be methylene dichloride, chloroform etc.Reduction reaction recommends to use solvent to be tetrahydrofuran (THF), methyl alcohol, ethanol, Virahol, the trimethyl carbinol etc., the Wittig reaction is recommended to use solvent to be methylene dichloride, chloroform, methyl-sulphoxide (DMSO), methyl alcohol, ethanol, N, N '-dimethyl formamide (DMF), or tetrahydrofuran (THF) etc.Hydrogenation is recommended to use solvent to be vinyl acetic monomer, methyl alcohol, ethanol, Virahol, the trimethyl carbinol etc.
Adopt and work as protecting group R in the compound 11 in the inventive method
5Be the acetals protecting group, when promptly protecting examination base that hydroxyl uses as benzyloxy methyl chloride, methoxychlor methane, dihydropyrane, 2-methoxy propyl-2-alkene or vinyl ethyl ether, above-mentioned hydrogenation liquid under violent condition, can be directly compound 3 or 4.Violent condition refers to higher reaction temperatures, the acid of longer reaction times or use higher concentration.
Alkyl acid ester cpds of the present invention can be used to prepare the optically active 4-methyl of tool-5-alkyl-δ-Wu Neizhi 3 or 4.Above-claimed cpd 1 or 2 react in pH＜0.01～5 6-person's macrolide compounds 3 or 4.Reaction solvent is water or organic solvent or the two mixture.Organic solvent can be methyl alcohol, ethanol, tetrahydrofuran (THF), methyl-sulphoxide, N, N '-dimethyl formamide, 1,4-dioxane.Reaction times is 0.2～80h.Temperature of reaction is-10 ℃～+ 180 ℃.
As mentioned above, compound of the present invention is simple synthetic method not only, and can be directly used in the synthetic of spices and seasonings.
Following examples will help to understand the present invention, but not limit content of the present invention.
Embodiment 1
N-propionyl-(S)-4-benzyl-sulphur azoles quinoline-2-thioketones (1mmol) is dissolved in methylene dichloride (5ml), and the ice-water bath cooling drips TiCl down
4(1mmol).Stir and add sparteine (2mmol) after 30 minutes.Add n-hexyl aldehyde (2mmol) then.Behind the reaction 1h, add the shrend reaction of going out, ether dilutes, and tells organic phase, dried over sodium sulfate, and silica gel column chromatography must slightly yellowy oily product, yield 60%.
1H?NMRδ7.40-7.20(m，5H)，5.37(m，1H)，4.51(dq，J＝3，7Hz，1H)，3.92(m，1H)，3.40(dd，J＝6.4，11Hz，1H)，3.23(dd，J＝3.8，13.2Hz，1H)，2.29(d，J＝11.5Hz，1H)，2.69(OH，1H)，1.40-1.20(m，8H)，1.26(d，J＝8.5Hz，3H)，0.90(t，J＝6.5Hz，3H).IR(film)：3401，1692，1455，1342，1262，1164，1030cm
-1。
Embodiment 2
N-propionyl-(R)-4-phenyl-oxazolines-2-ketone (1mmol) is dissolved in methylene dichloride (5ml), and-78 ℃ of coolings add Bu down
2BOTf (1mmol) and triethylamine (1.2mmol).After stirring lh.Add enanthaldehyde (2mmol) then.Behind the reaction 1h, add the shrend reaction of going out, drip 30% hydrogen peroxide (1ml) again.Reaction solution dilutes with ether, tells organic phase, dried over sodium sulfate, and silica gel column chromatography gets the oily product, yield 70%.
1H?NMRδ7.5-7.2(m，5H)，5.5(dd，J＝9，4Hz，1H)，4.7(t，J＝9Hz，lH)，4.3(dd，J＝4，9Hz，lH)，4.0(m，lH)，3.8(dd，J＝7，3Hz，1H)，2.9(br?s，1H)，1.65-1.21(m，10H)，1.2(d，J＝7Hz，3H)，0.9(t，J＝7Hz，3H).IR(film)：3539，1782，1753cm
-1.MS?m/z?316(M-17，45)，262(5)，233(55)，178(56)，120(43)，104(100)。
Embodiment 3
((2S, 3R)-2-methyl-3-hydroxyl) hexanoyl-(R)-4-benzyl-oxazolines-2-ketone (1mmol) is dissolved in methylene dichloride (5ml) to N-, and the ice bath cooling adds triethylamine (3mmol) and pivaloyl chloride (1mmol) down successively.Stirring at room 24h with ether dilution, tells organic phase, and dried over sodium sulfate must slightly yellowy oily product, is dissolved in ethanol (5ml), and the ice bath cooling adds Ca (BH down
4)
2(3mmol).Stirring at room 4h with the ether dilution, tells organic phase, dried over sodium sulfate, and silica gel column chromatography gets the oily product, yield 30% (2 step).
1H?NMRδ5.02(m，1H)，3.40(m，1H)，3.13(m，1H)，2.95(m，1H)，1.80-1.20(m，5H)，1.20(s，9H)，0.88(t，J＝6Hz，3H)，0.80(d，J＝7Hz，3H).MS?m/z?199(M-17，80)，115(40)，97(55)，85(42)，57(100)。
Embodiment 4
(2R, 3R)-2-methyl-3-dimethyl tertiary butyl siloxy-decyl alcohol (1mmol) is dissolved in chloroform (5ml), and the ice bath cooling adds PCC (3mmol) down.Stirring at room 4h with ether dilution, tells organic phase after the washing, dried over sodium sulfate, the organic phase rotary evaporation to do the oily product, be dissolved in ethanol (5ml), the ice bath cooling adds Wittig reagent Ph down
3P=CHCO
2Et (3mmol).Stirring at room 24h, with ether dilution, filtering solid, organic phase is spin-dried for, and silica gel column chromatography gets oily product (suitable, trans mixture), is dissolved in vinyl acetic monomer (15ml), adds 10% Pd/C (10mg contains 0.01mmol Pd approximately).Hydrogenation 24h under the room temperature normal pressure, the filtering solid, organic phase is spin-dried for, and gets the oily product, yield 60% (3 step).
1H NMR δ 4.15 (q, J=7Hz, 2H), 3.50 (dt, J=3,6Hz, 1H), 2.29 (m, 2H), 1.82 (m, 1H), 1.62-1.22 (m, 9H), 1.26 (t, J=7.1Hz, 3H), (0.90 s and t, J=5.8Hz, 16H altogether), 0.84 (d, J=6.6Hz, 3H), 0.04 (s, 6H) .IR 1740cm
-1.MS m/z 357 (M-15,18), 327 (18), 315 (100), 301 (11), 283 (5), 269 (51), 243 (60), 73 (54).
Embodiment 5
(4R, 5R)-2-methyl-3-olefin(e) acid methyl esters in benzyloxy-last of the ten Heavenly stems-2 (1mmol) is dissolved in vinyl acetic monomer (15ml), adds 10% Pd/C (10mg contains 0.01mmol Pd approximately).Hydrogenation 24h under the room temperature normal pressure, the filtering solid, organic phase is spin-dried for, and gets the oily product, yield 95%.
1H?NMRδ4.14(q，J＝7.1Hz，2H)，3.50(m，1H)，2.35(m，2H)，1.82(m，1H)，1.58-1.28(m，10H)，1.25(t，J＝7.1Hz，3H)，0.90(t，J＝6.6Hz，3H)，0.89(d，J＝6.3Hz，3H).IR(film)3480，1740cm
-1.MS?m/z?217(M+1，3).199(63)，171(5)，153(24)，74(100)。
Embodiment 6
(4R, 5R)-2-methyl-3-hydroxyl-capric acid isopropyl ester (1mmol) is dissolved in tetrahydrofuran (THF) (15ml), adds the H of 1N
2SO
4(1ml).React 24h under the room temperature, with ether dilution, Na
2CO
3Solution washing is told organic phase, dried over sodium sulfate, and the filtering solid, the organic phase rotary evaporation gets the oily matter of tool aromatic odour, yield 75% to doing behind the silica gel column chromatography.
1H?NMRδ4.29(m，1H)，2.54(br?t，J＝7.3Hz，2H)，2.30-1.95(m，2H)，1.78-1.60(m，2H)，1.60-1.40(m，2H)，1.40-1.20(m，5H)，0.90(d，J＝7.1Hz，3H)，0.90(t，J＝6.6Hz，3H).IR?1735cm
-1.MS?m/z?185(M+1，2)，167(0.7)，128(3)，113(25)，84(40)，56(100)，41(35)。
Claims (7)
1. one kind (4S, 5S)-and (4R, 5R)-Beta-methyl-γ-hydroxyl-alkyl acid and alkyl ester compound thereof, its molecular formula is shown in 1 and 2:
With
R wherein
1Be H or C
1-C
4Alkyl, R
2Be C
3-C
8Alkyl.
2. the preparation method of a compound as claimed in claim 1, it is characterized in that through following (1), (2), (3), (4) and (5), perhaps (1), (2), (3), (4), (5) and (6), perhaps the method for (1), (2), (3), (4), (5) and (7) makes:
(1) under organic solvent neutralization bases or acid effect, compound 7 usefulness hydroxyl protection reagent are carried out protection to hydroxyl, get compound 8, compound 7: hydroxyl protection reagent: alkali or acid=1: 1～10: 0.01～10, temperature of reaction is-80 ℃～+ 40 ℃, reaction times is 0.1～40h, described alkali is triethylamine, pyridine, diisopropyl ethyl amine, N, the N-Tetramethyl Ethylene Diamine, 1,8-diazabicyclo [5.4.0] undecane-7-alkene, sodium amide or sodium hydride, described acid is protonic acid or Lewis acid; Described protection reagent is benzyloxy methyl chloride, methoxychlor methane, trimethylchlorosilane, dimethyl tertiary butyl chloride silane, Acetyl Chloride 98Min., Benzoyl chloride, pivaloyl chloride, chloroformic acid first or ethyl ester, aceticanhydride, benzyl chlorine or benzyl bromine, dihydropyrane, 2-methoxy propyl-2-alkene or vinyl ethyl ether;
(2) the chirality prothetic group is removed in compound 8 usefulness metal borohydrides or the hydrogen reduction of aluminium lithium in organic solvent, get corresponding compounds 9, the mol ratio of reactant and reductive agent is 1: 0.25～20, temperature of reaction is-60 ℃～+ 60 ℃, reaction times is 0.1～30h, and described metal borohydride is lithium boron hydrogen, sodium borohydride, potassium boron hydrogen, calcium boron hydrogen or zinc boron hydrogen;
(3) in organic solvent, compound 9 gets compound 10 with the oxygenant effect, and the mol ratio of reactant and oxygenant is 1: 1～10, and temperature of reaction is-10 ℃+80 ℃, and the reaction times is 0.1～24h; Described oxygenant is oxalyl chloride-methyl-sulphoxide-triethylamine, Vanadium Pentoxide in FLAKES-methyl-sulphoxide-triethylamine, pyridinium chlorochromate or two chloro-chromic acid pyridines;
(4) under-10 ℃+80 ℃ temperature of organic solvent neutralization, compound 10 is 1: 1～4 with the mol ratio of Wittig reagent, and reaction 0.1～48h gets compound 11, and described Wittig reagent molecule formula is
R wherein
1Be H or C
1-C
4Alkyl;
(5) in the presence of the organic solvent catalyst neutralisation, compound 11 and hydrogen effect obtain the saturated derivative of two keys of compound 11 or work as used protecting group R
5During for benzyl or benzyloxymethyl, removing hydroxyl protecting group finishes when the two key of hydrogenation simultaneously, directly obtain compound 1 or 2, the hydrogenation temperature is-10 ℃～+ 50 ℃, the mol ratio of reactant and catalyzer is 1: 0.0001～1, reaction times is 0.1～24h, and hydrogen pressure is 0.1～3Mpa, and catalyst system therefor is Ra-Ni or Pd/C;
(6) as used protecting group R
5For benzoyl, acetyl, pivaloyl, first or ethoxycarbonyl, front three is silica-based or dimethyl tertiary butyl when silica-based; derivative that above-mentioned two keys are saturated or hydrogenation liquid are with the solution-treated of water, methyl alcohol, ethanol or the tetrahydrofuran (THF) of the alkali of 0.01～10N; transfer to pH neutrality; obtain removing the compound 1 or 2 that hydroxyl protecting group and ester group are hydrolyzed, wherein R
1=H, temperature of reaction is 20 ℃～60 ℃, and the reaction times is 1～48h, and the consumption of acid or alkali is the solution/molar reactive thing of above-mentioned acid of 0.1～10ml or alkali;
(7) as used protecting group R
5Be the acetals protecting group, the examination base that uses when promptly protecting hydroxyl is during as benzyloxy methyl chloride, methoxychlor methane, dihydropyrane, 2-methoxy propyl-2-alkene or vinyl ethyl ether, above-mentioned hydrogenation liquid is with the acid treatment of 0.01～10N, get compound 1 or 2, described acid is acetic acid, sulfuric acid, hydrochloric acid, tosic acid; Temperature of reaction is 20 ℃～60 ℃, and the reaction times is 1～48h, and the consumption of acid or alkali is the solution/molar reactive thing of above-mentioned acid of 0.1～10ml or alkali;
Above-claimed cpd 7,8, the following molecular formula of 9,10 and 11 difference tools:
R wherein
1Be H or C
1-C
4Alkyl, R
2Be C
3-C
8Alkyl is worked as R
3R during for hydrogen
4Be phenyl, sec.-propyl, benzyl; Work as R
4During for hydrogen, R
3Be phenyl, sec.-propyl, benzyl; R
5, ethanoyl silica-based for benzyloxymethyl, methoxymethyl, pivaloyl group, the dimethyl tertiary butyl, benzoyl or benzyl, X is Sauerstoffatom or sulphur atom.
3. preparation method as claimed in claim 2 is characterized in that compound 8,9,10 can not purifiedly be directly used in the next step.
4. preparation method as claimed in claim 2 is characterized in that described protonic acid or Lewis acid are sulfuric acid, hydrochloric acid, tosic acid or boron trifluoride.
5. preparation method as claimed in claim 2 is characterized in that described solvent can be a methylene dichloride, chloroform, tetrahydrofuran (THF), methyl alcohol, ethanol, Virahol, the trimethyl carbinol, chloroform, benzene, toluene, vinyl acetic monomer, methyl-sulphoxide or N, N '-dimethyl formamide.
6. the purposes of alkyl acid and alkyl ester compound thereof according to claim 1 is characterized in that being used to prepare spices and seasonings.
7. the purposes of its alkyl ester compound of alkyl acid according to claim 1, it is characterized in that being used for preparation (4S, 5S)-and (4R, 5R)-4-methyl-5-alkyl-δ-Wu Neizhi.
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|---|---|---|---|
| CNB011058803A CN1146534C (en) | 2001-04-06 | 2001-04-06 | (4S,5S)-and (4R,5R)-gamma-methyl-delta-hydroxyl-alkanoic acid and its alkyl ester, preparation method and application |
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|---|---|---|---|
| CNB011058803A CN1146534C (en) | 2001-04-06 | 2001-04-06 | (4S,5S)-and (4R,5R)-gamma-methyl-delta-hydroxyl-alkanoic acid and its alkyl ester, preparation method and application |
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|---|---|
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| CN1146534C true CN1146534C (en) | 2004-04-21 |
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