CN100548965C - ω-the hydroxy-acid derivative of band chirality methyl side chain - Google Patents
ω-the hydroxy-acid derivative of band chirality methyl side chain Download PDFInfo
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- CN100548965C CN100548965C CNB2004100932604A CN200410093260A CN100548965C CN 100548965 C CN100548965 C CN 100548965C CN B2004100932604 A CNB2004100932604 A CN B2004100932604A CN 200410093260 A CN200410093260 A CN 200410093260A CN 100548965 C CN100548965 C CN 100548965C
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Abstract
The present invention is a kind of ω-hydroxy-acid derivative with the chirality methyl side chain, has following general structure: be with 4R-4-methylpent lactone, and 3R-3-methyl butyrolactone, 4S-4-methylpent lactone, 3S-3-methyl butyrolactone is that starting raw material prepares.The invention provides the technology of chiral building block of bifunctional constitutional features that a kind of large-scale acquisition has the moderate-length of chirality methyl side chain.
Description
Technical field
This patent relates to the ω-hydroxy-acid derivative of band chirality methyl side chain, this compound can be optical purity 5-hydroxy-4-methyl valeric acid (4R-5-hydroxy-4-methyl valeric acid and a 4S-5-hydroxy-4-methyl valeric acid), the derivative of optical purity 4-hydroxy-3-methyl butyric acid (3R-4-hydroxy-3-methyl butyric acid and 3S-4-hydroxy-3-methyl butyric acid).They are with 4R-4-methylpent lactone, 4S-4-methylpent lactone, and 3R-3-methyl butyrolactone and 3S-3-methyl butyrolactone are that raw material can prepare in a large number easily.This compounds is very useful chiral building block.
Background technology
Chiral building block with bifunctional constitutional features of chirality methyl side chain, X (CH
2) mCHCH
3(CH
2) nY, in organic synthesis, have been widely used.These chiral building blocks can be used for the synthetic of chiral drugs such as vitamin-E, vitamin K, can be used for synthetic (K.Mori, Tetrahedron1989,45,3233 of insect sex pheromones such as Matsumura pine scale sex pheromone; Yan Fengming, chemical ecology, Science Press, 2003), can be used to have synthetic (Barton, S.D., Comprehensive Natural ProductsChemistry, Elsevier Science Ltd, 1999 of extensive bioactive natural product; Banfi, L et al, Synthesis, 1993,1029; Chen Daijie, microbial medicine is learned, press of East China University of Science, 1999), also as the synthetic monomeric raw material of ferroelectric liquid crystal material (Huang Weiyuan etc., hi-tech organic polymer material progress, Chemical Industry Press, 1994).Because its importance on biologically active substance and functional materials are synthetic and the popularity of application thereof, their synthetic special attention (Servi, S.Microbial reagents in organic synthesis, 399 of being subjected to, KluwerAcademic Publishers, 1992)
Chiral building block with bifunctional constitutional features of chirality methyl side chain can synthesize by the asymmetric synthesis technology, and method commonly used has by introducing chirality prothetic group (Evans reagent, S (R) AMP etc.) or direct and chiral substrates reaction (L-tartrate-(E)-crotyl, BINOL-TiX
2Deng).But the synthetic route is long, and the reagent costliness generally only only limits to laboratory gram level scale and synthesizes.Be prepared by biotechnology (as the asymmetric ester hydrolysis of microorganism), or to use the natural product (natural geraniol, geranial) contain chirality methyl to transform be the effective ways that this class chirality building block is provided on a large scale.But this class building block kind that can provide at present is limited, and oversize (＞7) or the carbochain of lacking very much (=3) are brought unfavorable factor to its application.Therefore, can to obtain to have the technology of chiral building block of bifunctional constitutional features of moderate-length of chirality methyl side chain on a large scale very necessary in development.
Steroid sapogenines, as sisalagenin, diosgenin, luxuriant numb sapogenin, zhimusaponin unit can obtain from renewable resources easily.They have by scale operation, and the basic raw material of producing as steroid drugs.In utilizing the steroid sapogenines resource at present, only utilize four loop sections of its A/B/C/D, the F loop section of bifunctional constitutional features with chirality methyl side chain is usually as offal treatment.What we had developed replaces the method for chromic anhydride oxidative degradation steroid sapogenines for obtain the optical purity methylpent from the steroid sapogenin degradation waste liquid with hydrogen peroxide, butyrolactone provides guarantee (Chinese patent 96116304.6, application number 00127974.2,01113196.9,0314164.1), yet this very easily polymerization of class optical purity methyl lactone, inconvenience is used, and must further be converted into stable compound.The present invention is translated into stable chain compound by the optical purity 4-methylpent lactone and the optical purity 3-methyl butyrolactone that obtain are transformed, and the Bifunctionalized synthetic building block of the band chirality methyl of a series of moderate-lengths is provided.
Summary of the invention
The object of the invention provides the ω-hydroxy-acid derivative of band chirality methyl side chain, specifically a kind of optical purity 4R-5-hydroxy-4-methyl valeric acid, 3R-4-hydroxy-3-methyl butyric acid, 4S-5-hydroxy-4-methyl valeric acid, the butyro-derivative of 3S-4-hydroxy-3-methyl
Have following general structure:
The object of the invention provides a kind of ω-hydroxy-acid derivative with the chirality methyl side chain, and their general structure is:
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, X=R
3Or OR
4, Y=C1-C10 alkyl, wherein R
3=chlorine, bromine, iodine ,=O, thiophenyl, benzene sulfoxide group, benzene sulfuryl, methylthio group, methyl sulfoxide base, methyl sulfuryl, ethylmercapto group, ethyl-sulfoxide base, ethyl sulfuryl, rosickyite base, propyl group sulfoxide group or propyl group sulfuryl, R
4The alkyl of=H, C1-C4, benzyl, to methoxybenzyl, p-chlorobenzyl, ethanoyl, propionyl, benzoyl (Bz), methoxyl methyl, ethoxymethyl, trimethyl silicon based, triethyl is silica-based, the dimethyl tertiary butyl is silica-based or the phenylbenzene tertiary butyl is silica-based;
Wherein:
1) works as R
1=H, R
2=Me, the n=0:(R configuration)
Y＝Me，X≠OH，OTBDMS，＝O；
During Y=Et, X ≠ Br, I, SPh;
During Y=t-Bu, X ≠ OH, OTBDMS, OTs;
2) work as R
1=H, R
2=Me, the n=0:(S configuration)
Y＝Me，X≠Br，I，SO
2Ph，＝O；
During Y=Et, X ≠ OH, Br, I, SPh, ethoxy methoxyl group, OBn;
During Y=t-Bu, X ≠ OH;
3) work as R
1=H, R
2=Me, the n=1:(R configuration)
Y＝Me，X≠OH，Br，OAc，OTBDMS，＝O；
During Y=Et, X ≠ OH, Br, OTBDMS;
During Y=t-Bu, X ≠ OH ,=O;
4) work as R
1=H, R
2=Me, the n=1:(S configuration)
Y＝Me，X≠＝O；
During Y=Et, X ≠ OTBDMS;
Wherein=O constitutes that aldehyde radical, Bn are that benzyl, Ac are that ethanoyl, TBDMS are that the dimethyl tertiary butyl is silica-based on the carbon.
Compound of the present invention can be optical purity 4R-5-hydroxy-4-methyl valeric acid furtherly, 3R-4-hydroxy-3-methyl butyric acid, and 4S-5-hydroxy-4-methyl valeric acid, the butyro-derivative of 3S-4-hydroxy-3-methyl etc., the compound that its structural formula can be following:
Wherein Bz is a benzoyl, and MOM is a methoxyl methyl, and Bn, Ac and TBDPS are as mentioned above.
ω-the hydroxy-acid derivative of band chirality methyl side chain of the present invention with structural formula is
Optically pure Beta-methyl butyrolactone or γ-methylpent lactone be raw material, wherein R
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1.Specifically with 4R-4-methylpent lactone, 3R-3-methyl butyrolactone, 4S-4-methylpent lactone, 3S-3-methyl butyrolactone is that starting raw material prepares.
In the method for the present invention, above-mentioned optically pure lactone uses following method to carry out open loop:
A) in alcohol, as methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, 2-butanols, isopropylcarbinol or the trimethyl carbinol etc., lactone and acid (sulfuric acid, haloid acid, nitric acid, phosphoric acid, p-methyl benzenesulfonic acid, methylsulphonic acid or acidic resins) or alkali (sodium hydroxide, sodium methylate or sodium ethylate), to reflux temperature reaction 0.5-50 hour, obtain opened loop compound in room temperature, described lactone is 1 with the mol ratio of alcohol: 1-1000, lactone is 1 with the mol ratio of acid: 0.01-1, the mol ratio of lactone and alkali is 1: 0.01-1.
B) at inert solvent (ether, tetrahydrofuran (THF), sherwood oil, normal hexane, benzene or toluene) or alcohol (methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, 2-butanols, isopropylcarbinol or the trimethyl carbinol) in, lactone and nucleophilic reagent to reflux temperature reaction 0.5-50 hour, obtain opened loop compound in room temperature.Nucleophilic reagent is HX
1(X
1=Cl, Br, I), and HSR (R=H, the alkyl of C1-C10, phenyl or benzyl), the dimethoxy formal, the mol ratio of described lactone and solvent or alcohol is 1: 1-1000, the mol ratio of lactone and nucleophilic reagent is 1: 1-20.
Invention major advantage of the present invention has:
1) made full use of optical purity 4-methylpent lactone in the hydrogen peroxide oxidation degradation of steroid sapogenin waste liquid, 3-methyl butyrolactone.Pollute and lack, the productive rate height, aftertreatment is simple, has utilized resource fully.
2) the 4-methylpent lactone of degrading and obtaining, the easy polymerization of 3-methyl butyrolactone, inconvenience is used and is preserved, the present invention is transformed into the chiral building block of the bifunctional constitutional features of the convenient moderate-length with chirality methyl side chain that uses with it, this class chirality building block can be used as to synthesize and contains the natural product of chirality methyl and the starting raw material of medicine, uses other synthetic this compounds of method very complicated.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, Y=C1-C4 alkyl 4R-5-hydroxy-4-methyl-isopropyl isovalerate
Under 1 gram Hydrogen bromide catalysis, 11.4 gram 4R-4-methyl-valerolactones (polymer and monomeric mixture) refluxed 2 hours in the 20mL anhydrous isopropyl alcohol, ether extraction, and washing, dried over mgso is drained to such an extent that 16.2 restrain 4R-5-hydroxy-4-methyl-isopropyl isovalerates.Yield 93%.
C9H18O3：(174.24)
Ultimate analysis: C%=62.24; H%=10.23; Mass spectrum: (M
+, 174)
1HNMR(300MHz，CDCl
3)δ：4.32(m，1H)，3.45(d，J＝6.3Hz，2H)，2.2-2.6(m，3H)，1.3-1.7(m，3H)，1.34(d，J＝3.6Hz，6H)，0.89(d，J＝6.3Hz，3H)。
Use aforesaid method to synthesize:
4S-5-hydroxy-4-methyl-valeric acid the tert-butyl ester (productive rate 75%),
Ultimate analysis: C%=63.64; H%=10.53; Mass spectrum: (M
+, 188);
3R-4-hydroxy-3-methyl-ethyl butyrate (productive rate 90%),
Ultimate analysis: C%=57.42; H%=10.01; Mass spectrum: (M
+, 146);
3S-4-hydroxy-3-methyl-methyl-butyrate (productive rate 94%),
Ultimate analysis: C%=54.4; H%=9.50; Mass spectrum: (M
+, 132).
Embodiment 2
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, Y=C1-C4 alkyl 4R-5-oxo-4-methyl-Valeric acid ethylester
With the synthetic 4R-5-hydroxy-4-methyl-Valeric acid ethylester of the method for embodiment 1.
4R-5-hydroxy-4-methyl-Valeric acid ethylester is dissolved in the 10ml methylene dichloride for 500 milligrams, adds 1.2eq chromic acid pyridinium salt (PDC), and stirring at room 20 minutes is filtered, and filtrate washing twice is spin-dried for solvent, and column chromatography obtains 420 milligrams of water white oils.Productive rate 84%.
C8H14O3：(158.19)
Ultimate analysis: C%=61.14; H%=8.45; Mass spectrum: (M
+, 158)
1HNMR(300MHz，CDCl
3)δ：9.63(s，1H)，3.65(m，2H)，2.4(m，1H)，2.38(d，J＝7.5Hz，2H)，2.1(m，1H)，1.7(m，1H)，1.34(t，J＝6.6Hz，3H)，1.13(d，J＝7.2Hz，3H)。
Use aforesaid method to synthesize:
3R-4-oxygen-3-methyl-ethyl butyrate (productive rate 80%),
Ultimate analysis: C%=58.04; H%=8.60; Mass spectrum: (M
+, 144);
3S-4-oxygen-3-methyl-tert-butyl acetate (productive rate 84%),
Ultimate analysis: C%=62.65; H%=9.53; Mass spectrum: (M
+, 172).
Embodiment 3
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, X
1=Cl, Br, Y=C1-C4 alkyl 4R-5-chloro-4-methyl-methyl valerate
11.4 gram 4R-4-methyl-valerolactone (polymer and monomeric mixture) is dissolved in the 50mL anhydrous methanol, feed 30 gram HCl gases, stirred 1 hour, ether extraction, be washed to neutrality, dried over mgso is drained, and underpressure distillation gets colorless oil 4R-5-chloro-4-methyl-methyl valerate 13.6 grams of 46 ℃/0.2mmHg.Yield 83%.
C7H13ClO2：(164.63)
Ultimate analysis: C%=51.37; H%=8.25;
Mass spectrum: (M
+, 164)
1HNMR(300MHz，CDCl
3)δ：3.69(s，3H)，3.38(m，2H)，2.35(m，2H)，1.8(m，2H)，1.6(m，1H)，1.03(d，J＝6.3Hz，3H)。
The 4S-5-iodo-4-methyl-valeric acid tert-butyl ester
Synthesized 4S-5-bromo-4-methyl-valeric acid tert-butyl ester with above-mentioned method,
The 4S-5-bromo-4-methyl-valeric acid tert-butyl ester 2.5 grams are dissolved in 20mL acetone, add 10 equivalent NaI, stirring at room 2 days, and ether extraction is washed three times.Be spin-dried for solvent, column chromatography obtains 2.3 gram incarnadine oil (77%).
C10H19IO2：(298.16)
Ultimate analysis: C%=40.78; H%=6.22; Mass spectrum: (M
+, 298)
1HNMR(300MHz，CDCl
3)δ：3.15(m，2H)，2.3(m，2H)，1.7(m，2H)，1.65(s，9H)，1.5(m，1H)，1.10(d，J＝6.3Hz，3H)。
Use aforesaid method to synthesize:
3R-4-bromo-3-methyl-methyl-butyrate (productive rate 82%),
Ultimate analysis: C%=36.45; H%=5.74; Mass spectrum: (M
+, 194);
3S-4-bromo-3-methyl-butyl butyrate (productive rate 84%),
Ultimate analysis: C%=45.68; H%=7.21; Mass spectrum: (M
+, 236);
4S-5-iodo-4-methyl-methyl valerate (productive rate 73%),
Ultimate analysis: C%=33.14; H%=5.22; Mass spectrum: (M
+, 256).
Embodiment 4
R1=H wherein, R2=Me or R1=Me, R2=H, n=0 or 1, PG are hydroxyl protecting group, the Y=C1-C4 alkyl.
4R-5-methoxy methoxy base-4-methyl-methyl valerate
29 gram 4R-5-hydroxy-4-methyl-methyl valerates are dissolved in the 200mL methylene dichloride, add 28 gram DBU (1,8 diaza-bicyclo [5,4,0], 11-7-alkene) and 17 gram chloromethane oxygen methylmethanes, stirring at room 4 hours, product washing twice, dried over mgso.Be spin-dried for solvent, 50 ℃/0.2mmHg of underpressure distillation obtains 37.5 gram water white oils.Productive rate 98%.
C9H18O4：(190.24)
Ultimate analysis: C%=56.78; H%=9.22; Mass spectrum: (M
+, 190)
1HNMR(300MHz，CDCl
3)δ：4.61(s，2H)，3.67(s，3H)，3.37(d，J＝3.9Hz，2H)，3.36(s，3H)，2.4(m，2H)，1.8(m，2H)，1.5(m，1H)，0.94(d，J＝6.6Hz，3H)。
Use aforesaid method to synthesize:
3R-4-benzyloxy-3-methyl-butyl butyrate (productive rate 72%),
Ultimate analysis: C%=72.49; H%=9.35; Mass spectrum: (M
+, 264);
3S-4-tert-butyl diphenyl siloxy-3-methyl-ethyl butyrate (productive rate 94%),
Ultimate analysis: C%=71.43; H%=8.42; Mass spectrum: (M
+, 384);
4R-5-benzoyloxy-4-methyl-butyl valerate (productive rate 83%),
Ultimate analysis: C%=68.55; H%=8.34; Mass spectrum: (M
+, 292);
4S-5-ethoxy methoxyl group-4-methyl-butyl valerate (productive rate 93%),
Ultimate analysis: C%=63.45; H%=10.74; Mass spectrum: (M
+, 246).
Embodiment 5
R1=H wherein, R2=Me or R1=Me, R2=H, n=0 or 1, X2=methylthio group, ethylmercapto group, rosickyite base and thiophenyl, Y=C1-C4 alkyl.
4R-5-thiophenyl-4-methyl-methyl valerate
2.0 gram 4R-4-methyl-valerolactone (polymer and monomeric mixture) is dissolved in the 20ml anhydrous methanol, adds 1.5 equivalent sodium methylates, 1.2 equivalent benzenethiols, and stirring at room 1 hour, the product ether extraction is washed to neutrality, dried over mgso.Be spin-dried for solvent, column chromatography obtains 2.4 gram water white oils.Productive rate 72%.
C13H18O2S：(238.35)
Ultimate analysis: C%=65.32; H%=7.36; Mass spectrum: (M
+, 238)
1HNMR(300MHz，CDCl
3)δ：7.0-7.2(m，5H)，3.81(s，3H)，2.8(m，2H)，2.2(m，2H)，1.9(m，1H)，1.6(m，2H)，0.99(d，J＝6.3Hz，3H)。
Use aforesaid method to synthesize:
3R-4-ethylmercapto group-3-methyl-methyl-butyrate (productive rate 69%),
Ultimate analysis: C%=54.53; H%=8.73; Mass spectrum: (M
+, 176);
3S-4-thiophenyl-3-methyl-methyl-butyrate (productive rate 65%),
Ultimate analysis: C%=64.32; H%=7.32; Mass spectrum: (M
+, 224);
4S-5-thiophenyl-4-methyl-Valeric acid ethylester (productive rate 70%),
Ultimate analysis: C%=66.65; H%=8.24; Mass spectrum: (M
+, 252).
Embodiment 6
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, X2=methylthio group, ethylmercapto group, rosickyite base and thiophenyl, X3=methyl sulfuryl, ethyl sulfuryl, propyl group sulfuryl and phenyl sulfuryl, Y=C1-C4 alkyl 4R-5-benzene sulfuryl-4-methyl-methyl valerate
1.2 gram 4R-5-thiophenyl-4-methyl-methyl valerate is dissolved in the 20ml ethyl acetate, adds 2 equivalents, six water iron nitrates, stirring at room 2 hours, product washing, dried over mgso.Be spin-dried for solvent, the 1.2 gram water white oils that column chromatography obtains are dissolved in the 100ml ethyl acetate, add 1.2 equivalent 70%m-CPBA, stirring at room 2 hours, product Na
2CO
3Wash washing, dried over mgso.Be spin-dried for solvent, column chromatography obtains 1.1 gram water white oils.Productive rate 86%.
C13H18O4S：(270.34)
Ultimate analysis: C%=57.43; H%=6.72; Mass spectrum: (M
+, 270)
1HNMR(300MHz，CDCl3)δ：7.8-7.4(m，5H)，3.66(s，3H)，3.1-2.9(m，2H)，2.29(m，2H)，2.13(m，1H)，1.80(m，1H)，1.55(m，1H)，1.09(d，J＝6.7Hz，3H)。
Use aforesaid method to synthesize:
3R-4-ethyl sulfone-3-methyl-methyl-butyrate (productive rate 85%),
Ultimate analysis: C%=46.48; H%=7.54; Mass spectrum: (M
+, 204);
4S-5-benzene sulfuryl-4-methyl-Valeric acid ethylester (productive rate 86%),
Ultimate analysis: C%=59.24; H%=7.45; Mass spectrum: (M
+, 284)
Claims (7)
1. preparation method with the ω-hydroxy-acid derivative of chirality methyl side chain, it is characterized in that by following method a) or b) make:
A) in alcohol, optically pure Beta-methyl butyrolactone or γ-methylpent lactone and acid or alkali reacted 0.5-50 hour to reflux temperature in room temperature, obtain opened loop compound, described lactone is 1 with the mol ratio of alcohol: 1-1000, lactone is 1 with the mol ratio of acid: 0.01-1, and the mol ratio of lactone and alkali is 1: 0.01-1;
B) in inert solvent or alcohol, Beta-methyl butyrolactone or γ-methylpent lactone and nucleophilic reagent reacted 0.5-50 hour to reflux temperature in room temperature, obtain opened loop compound, the mol ratio of described Beta-methyl butyrolactone or γ-methylpent lactone and solvent or alcohol is 1: 1-1000, and the mol ratio of Beta-methyl butyrolactone or γ-methylpent lactone and nucleophilic reagent is 1: 1-20; Described nucleophilic reagent is HSR or dimethoxy formal; Wherein, the alkyl of R=H, C1-C10, phenyl or benzyl;
ω-the hydroxy-acid derivative of wherein said band chirality methyl side chain has following general structure;
R wherein
1=H, R
2=Me or R
1=Me, R
2=H, n=0 or 1, X=R
3Or OR
4, Y=C1-C10 alkyl, wherein R
3=chlorine, bromine, iodine ,=O, thiophenyl, benzene sulfoxide group, benzene sulfuryl, methylthio group, methyl sulfoxide base, methyl sulfuryl, ethylmercapto group, ethyl-sulfoxide base, ethyl sulfuryl, rosickyite base, propyl group sulfoxide group or propyl group sulfuryl, R
4The alkyl of=H, C1-C4, benzyl, to methoxybenzyl, p-chlorobenzyl, ethanoyl, propionyl, benzoyl, methoxyl methyl, ethoxymethyl, trimethyl silicon based, triethyl is silica-based, the dimethyl tertiary butyl is silica-based or the phenylbenzene tertiary butyl is silica-based;
Wherein:
1) as R configuration, R
1=H, R
2=Me, n=0:
Y＝Me，X≠OH，OTBDMS，＝O；
During Y=Et, X ≠ Br, I, SPh;
During Y=t-Bu, X ≠ OH, OTBDMS;
2) as S configuration, R
1=H, R
2=Me, n=0:
Y＝Me，X≠Br，I，SO
2Ph，＝O；
During Y=Et, X ≠ OH, Br, I, SPh, ethoxy methoxyl group, OBn;
During Y=t-Bu, X ≠ OH;
3) as R configuration, R
1=H, R
2=Me, n=1:
Y＝Me，X≠OH，Br，OAc，OTBDMS，＝O；
During Y=Et, X ≠ OH, Br, OTBDMS;
During Y=t-Bu, X ≠ OH ,=O;
4) as S configuration, R
1=H, R
2=Me, n=1:
Y＝Me，X≠＝O；
During Y=Et, X ≠ OTBDMS;
Wherein Bn is that benzyl, Ac are that ethanoyl, TBDMS are that the dimethyl tertiary butyl is silica-based.
2. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1, the ω-hydroxy-acid derivative that it is characterized in that described band chirality methyl side chain is to have following structural formula:
Wherein Bz is a benzoyl, and MOM is a methoxyl methyl, and Bn is a benzyl, and TBDPS is that the phenylbenzene tertiary butyl is silica-based.
3. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1 is characterized in that described optically pure Beta-methyl butyrolactone and γ-methylpent lactone are optically pure 4R-4-methylpent lactone, 3R-3-methyl butyrolactone, 4S-4-methylpent lactone or 3S-3-methyl butyrolactone.
4. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1 is characterized in that described alcohol is methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, 2-butanols, isopropylcarbinol or the trimethyl carbinol.
5. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1 is characterized in that described acid is sulfuric acid, haloid acid, nitric acid, phosphoric acid, p-methyl benzenesulfonic acid, methylsulphonic acid or acidic resins.
6. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1 is characterized in that described alkali is sodium hydroxide, sodium methylate or sodium ethylate.
7. the preparation method of the ω-hydroxy-acid derivative of band chirality methyl side chain as claimed in claim 1 is characterized in that described inert solvent is ether, tetrahydrofuran (THF), sherwood oil, normal hexane, benzene or toluene.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3145455A1 (en) * | 1981-11-16 | 1983-05-26 | Basf Ag, 6700 Ludwigshafen | (3R,7R)-3,7,11-Trimethyl-5-dodecenes substituted in the 1-position, their use as intermediate for the synthesis of the side chain of (R,R,R)- alpha -tocopherol and their preparation from starting compounds some of which are novel |
| CN1146457A (en) * | 1996-04-03 | 1997-04-02 | 中国科学院上海有机化学研究所 | Method for preparation of progestol by degradation of steroidal saponin |
-
2004
- 2004-12-21 CN CNB2004100932604A patent/CN100548965C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3145455A1 (en) * | 1981-11-16 | 1983-05-26 | Basf Ag, 6700 Ludwigshafen | (3R,7R)-3,7,11-Trimethyl-5-dodecenes substituted in the 1-position, their use as intermediate for the synthesis of the side chain of (R,R,R)- alpha -tocopherol and their preparation from starting compounds some of which are novel |
| CN1146457A (en) * | 1996-04-03 | 1997-04-02 | 中国科学院上海有机化学研究所 | Method for preparation of progestol by degradation of steroidal saponin |
Non-Patent Citations (7)
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| 《A new and general synthesis of chiral b-keto sulfoxides byreaction of (+)-(R)-methyl p-tolyl sulfoxide with nitriles》. Robert，Vleggaar等.《Tetrahedron Letters》，第40卷第52期. 1999 |
| 《A new and general synthesis of chiral b-keto sulfoxides byreaction of (+)-(R)-methyl p-tolyl sulfoxide with nitriles》. Robert,Vleggaar等.《Tetrahedron Letters》，第40卷第52期. 1999 * |
| 《Acylation of alkyl halides and amino aldehydes with aphosphane oxide-based d1-synthon.》. Marco，Brunjes等.《European Journal of Organic Chemistry》，第5期. 2004 |
| 《Acylation of alkyl halides and amino aldehydes with aphosphane oxide-based d1-synthon.》. Marco,Brunjes等.《European Journal of Organic Chemistry》，第5期. 2004 * |
| 《Asymmetric synthesis of 3-substituted 4-oxo esters usingtheSAMP-/RAMP-hydrazone method》. D.，Enders等.《Molecules Online》，第2卷第1期. 1998 |
| 《Highly enantioselective rhodium-catalyzed hydrogenation of2-(2-methoxy-2-oxoethyl)acrylic acid - A convenient access ofenantiomerically pure isoprenoid building blocks.》. Markus，Ostermeier等.《European Journal of Organic Chemistry》，第17期. 2003 |
| 《Towards a synthesis of epothilone A: asymmetric synthesisof C(1)-C(6) and C(7)-C(15) fragments》. S.，Chandrasekhar等.《Tetrahedron》，第13卷第3期. 2002 |
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| CN1660766A (en) | 2005-08-31 |
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