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使用D-(-)樟脑衍生物-莰烷-2,10-磺内酰胺为原料,以N-烷酰基莰烷-2,10-磺内酰2胺与碘代烷基化合物进行不对称烷基化反应为关键步骤,共经3步成功地合成出(R)和(S)-2-甲基戊酸,其光学纯度大于95%e.e。本文合成方法具有合成步骤短,产率高,反应条件温和及手性助剂可回收利用等优点,是一种合成各种2-甲基链烷酸的简捷,有效的好方法。 相似文献
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Prazeres VF Sánchez-Sixto C Castedo L Lamb H Hawkins AR Riboldi-Tunnicliffe A Coggins JR Lapthorn AJ González-Bello C 《ChemMedChem》2007,2(2):194-207
Isomeric nitrophenyl and heterocyclic analogues of the known inhibitor (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid have been synthesized and tested as inhibitors of M. tuberculosis and S. coelicolor type II dehydroquinase, the third enzyme of the shikimic acid pathway. The target compounds were synthesized by a combination of Suzuki and Sonogashira cross-coupling and copper(I)-catalyzed 2,3-dipolar cycloaddition reactions from a common vinyl triflate intermediate. These studies showed that a para-nitrophenyl derivative is almost 20-fold more potent as a competitive inhibitor against the S. coelicolor enzyme than that of M. tuberculosis. The opposite results were obtained with the meta isomer. Five of the bicyclic analogues reported herein proved to be potent competitive inhibitors of S. coelicolor dehydroquinase, with inhibition constants in the low nanomolar range (4-30 nM). These derivatives are also competitive inhibitors of the M. tuberculosis enzyme, but with lower affinities. The most potent inhibitor against the S. coelicolor enzyme, a 6-benzothiophenyl derivative, has a K(i) value of 4 nM-over 2000-fold more potent than the best previously known inhibitor, (1R,4R,5R)-1,5-dihydroxy-4-(2-nitrophenyl)cyclohex-2-en-1-carboxylic acid (8 microM), making it the most potent known inhibitor against any dehydroquinase. The binding modes of the analogues in the active site of the S. coelicolor enzyme (GOLD 3.0.1), suggest a key pi-stacking interaction between the aromatic rings and Tyr 28, a residue that has been identified as essential for enzyme activity. 相似文献
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(2S,3R)-2羟基-3-氨基-4-苯基丁酸(AHPBA)是制备Bestatin、Phebestin和Probestin等氨肽酶N(Aminopeptide N)抑制剂的关键中间体。本文从氨基酸法(D-苯丙氨酸、L-天门冬氨酸、苹果酸二酯)、有机金属催化法(双功能铝配合物)、酶催化法(脂肪酶和全细胞酶)以及其它方法对此中间体的合成方法及路线进行综述和分析。经比较,有机催化法、酶法以及苯乙酮法因其具有经济有利、条件温和或路线简单特点,具有潜在的工业化应用前景。同时,未来人们对AHPBA的合成开发将集中在对已有工艺路线的改进与优化。 相似文献
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Jovanka Huguet Michel Vert Michel Reix Maurice Sepulchre Nicolas Spassky 《Polymer》1979,20(8):961-968
Stereoisomers of N-(sec-butyl)-N-methyl-N-((R,S)-thiirane 2-ylmethyl) amine ((S)-sec-butyl, optical purity O.P. ~94% and (R)-sec-butyl, O.P. ~26%) were polymerized using a chiral initiator system (1:1) (R(-)BMBD) (stereoelective polymerization). In agreement with the homosteric character of this initiator, the configuration of the asymmetric centre located in the heterocycle of the elected diastereoisomer is shown to be R from c.d. spectra of residual monomers, whatever the configuration of the asymmetric centre located in the pendant group. O.r.d. and c.d. spectra of stereoelected polydiastereoisomers are described and compared to those of corresponding polydiastereoisomers bearing racemic main-chain chiral centres. 13C n.m.r. spectra of different polydiastereoisomers are reported. The stereosensitivity to tacticity of the main-chain carbons is poor but some of the side-chain carbon atoms are very sensitive to the presence of two asymmetric centres per repeat unit. The optical purity of main-chain chiral centres is deduced from the split resonance of one of these carbons atoms. It is shown that chiroptical properties of polydiastereoisomers primarily depend on configurations of the two chiral sites without obvious contributions from macromolecular conformations. The 242 nm c.d. band assigned to the n → σ1 electronic transition of sulphur chromophores is sensitive only to the optical purity of main-chain chiral centres and can be used to evaluate the configurational enrichment due to the stereoelective polymerization. 相似文献
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采用格氏试剂C6H13MgBr和C10H2MgBr对光学活性O-TMS保护的(R)-氰醇的氰基加成,随之用NaBH4对亚胺化合物立体诱导还原氢化,以98%的de值合成了两个新的手性试剂(1R,2S)-2-氨基醇,产率分别达到59%和62%.并通过X射线单晶结构分析法测定了分子结构和晶体结构. 相似文献
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本文介绍了羟基天冬氨酸合成的,以D-酒石酸二乙酯为原料,与氯化亚砜反应成亚磺酸类化合物,再与叠氮化钠发生开环反应后,催化加氢还原后得到羟基天冬氨酸二乙酯,经皂化反应后得到目标产物,四步反应的总收率为42.04%。 相似文献
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(1S,5R,6R,7R)-6-羟甲基-7-羟基-2-氧杂双环[3.3.0]辛-3-酮(Ⅵ)是制备前列腺素的关键中间体。为了简化工艺条件,降低生产成本,以环戊二烯和二氯乙酰氯为原料,经环加成、还原和Baeyer-Villiger氧化3步反应制得2-氧杂双环[3.3.0]辛-6-烯-3-酮(Ⅳ),收率83.9%;经光学拆分后,与多聚甲醛经区域选择性Prins反应、粗产品不经分离,直接水解合成了Ⅵ,总收率22.0%。讨论了拆分剂、结晶溶剂对拆分Ⅳ的作用,确定了以R-(+)-苯乙胺为拆分剂,乙酸乙酯为结晶溶剂来拆分Ⅳ,拆分收率34.3%,[α]D20=-104.0°(c=1.0,MeOH),熔点:42~46℃。对Prins反应后水解产物的后处理工艺进行了优化,用氯仿重结晶代替柱分离来精制产品,收率76.5%,[α]D20=-45.0°(c=1.0,MeOH),熔点:117~119℃。目标产物用IR、MS、1HNMR进行了表征。 相似文献
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Berens U Hafner A Dosenbach O Tritschler T Schwarzenbach F Kirner HJ Malan C Mai-Huynh O 《Chimia》2010,64(1-2):59-64
The first highly enantioselective, catalytic asymmetric synthesis of di-des-methylsibutramine 3 is described. Dienamide 10, prepared by acetic acid anhydride quenching of the condensation product of nitrile 4 with a methallyl magnesium chloride, proved to be an excellent substrate for ruthenium-catalyzed asymmetric hydrogenation with atropisomeric diphosphine ligands. Hydrogenation with a ruthenium/(R)- MeOBiPheP catalyst at S/C = 500, gave the chiral amide (R)-9 in 98.5% ee in almost quantitative yield. After acidic amide hydrolysis the desired amine (R)-3 was obtained without erosion of enantioselectivity. It is anticipated that the overall process will be amenable to large-scale production. 相似文献
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替卡格雷是一种口服选择性小分子抗凝血药,不需要通过代谢激活,自身具有抗血小板活性。(1R,2S)-2-(3,4-二氟苯基)环丙胺是合成替卡格雷的一个关键中间体。该文在文献报道的合成路线基础上对其中关键步骤——不对称Corey-Chaykovsky环丙烷化反应进行了研究,筛选出最优反应条件:以L-薄荷醇为手性辅剂,三甲基碘化锍盐为硫叶立德试剂,二甲亚砜和四氢呋喃为混合溶剂,温度为10~12℃,质量分数10%的碘化亚铜为催化剂时,反应收率为60.5%;合成(1R,2S)-2-(3,4-二氟苯基)环丙胺5步总收率为20.0%。 相似文献
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De Capua A Goodman M Amino Y Saviano M Benedetti E 《Chembiochem : a European journal of chemical biology》2006,7(2):377-387
We report here the synthesis and the conformation analysis by 1H NMR spectroscopy and computer simulations of six potent sweet molecules, N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-S-tert-butyl-L-cysteine 1-methylester (1; 70 000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-beta-cyclohexyl-L-alanine 1-methylester (2; 50 000 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-4-cyan-L-phenylalanine 1-methylester (3; 2 000 times more potent than sucrose), N-[3,3-dimethylbutyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (4; 5500 times more potent than sucrose), N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (5; 15 000 times more potent than sucrose), and N-[3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl]-alpha-L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide (6; 15 000 times more potent than sucrose). The "L-shaped" structure, which we believe to be responsible for sweet taste, is accessible to all six molecules in solution. This structure is characterized by a zwitterionic ring formed by the AH- and B-containing moieties located along the +y axis and by the hydrophobic group X pointing into the +x axis. Extended conformations with the AH- and B-containing moieties along the +y axis and the hydrophobic group X pointing into the -y axis were observed for all six sweeteners. For compound 5, the crystal-state conformation was also determined by an X-ray diffraction study. The result indicates that compound 5 adopts an L-shaped structure even in the crystalline state. The extraordinary potency of the N-arylalkylated or N-alkylated compounds 1-6, as compared with that of the unsubstituted aspartame-based sweet taste ligands, can be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the L-shaped structure. In our examination of the unexplored D zone of the Tinti-Nofre model, we discovered a sweet-potency-enhancing effect of arylalkyl substitution on dipeptide ligands, which reveals the importance of hydrophobic (aromatic)-hydrophobic (aromatic) interactions in maintaining high potency. 相似文献
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Sun Xingyuan Shi Hanbing Bi Hongxia Ou Zhimin 《Korean Journal of Chemical Engineering》2013,30(1):166-171
Tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate was synthesized using asymmetric reduction of tert-butyl (S)-6-chloro-5-hydroxy-3-oxo-hexanoate with liquid-core immobilized Saccharomyces cerevisiae CGMCC No. 2233. The optimum conditions for preparation of the liquid-core immobilized cells were found to be 2% guar gum, 5% CaCl2, 0.8% sodium alginate, capsule diameter 2mm, 0.3% chitosan (1.0×105) solution, and 30 min for formation of the film of liquid-core immobilized cells. The optimum re-cultivation time was 32 h. The optimum reduction conditions were found to be pH 6.8–7.2, 160 r/min, and 30 °C. Conversion was found to reach 100% when initial concentration of substrate was less than 50 g/L. The diastereomeric excess of tert-butyl (3R,5S)-6-chloro-3,5-dihydroxyhexanoate exceeded 99%. The liquid-core immobilized cells retained their effectiveness even after 15 uses. 相似文献
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