关键词： 去消旋化   手性   生物催化  

摘要： 生物催化去消旋化是利用微生物或酶对底物进行高度立体选择性序列生物转化,得到所需的单一光学异构体的方法,并可达到100%的产率和对映体过量率.而传统的拆分法仅能获得最高50%的产率,还需要繁琐的步骤来分离反应原料和产物.因此,去消旋化作为一个简便而有效的方法越来越得到人们的重视.本文中,笔者就去消旋化在不对称合成中的应用进行了综述.

关键词： asymmetric catalysis   cross-coupling   enantioselectivity   palladium  

摘要： Palladium-catalyzed coupling reactions are some of the most widely used andreliable transformations available to organic chemists, and it is therefore not surprising that theefforts taken to adapt these key transformations to asymmetric processes are ongoing. The use ofenantiomerically pure palladium catalysts in inter- and intramolecular Heck reactions is wellestablished and has been applied to a number of successful total syntheses. The systems studied inHeck reactions generally involve carbon-carbon double bond transposition, thus resulting in thestereoselective formation of a new sp~3 center. The development of enantioselective cross-couplingreactions, such as Suzuki and Stille couplings, is more complex, in that generally the reactionsresult in the union of two sp~2 centers with no stereogenic sp~3 centers being produced. An elegantsolution, reported recently by the research groups of both Buchwald and Cammidge, is to use Suzukicoupling reactions to produce axially chiral systems. Hayashi et al. have developed ametal-catalyzed asymmetric biaryl synthesis; a desymmetrization approach was employed to allowpalladium- and nickel-catalyzed enantioselective Kumada couplings to generate axially chiral systemswith high selectivities. A similar approach has also been employed to prepare systems containingplanar chirality. Herein, we utilize a desymmetrization strategy to detail the first report on theintermolecular enantioselective Suzuki couplings that produce compounds containing stereodefinedsp~3 carbon centers

关键词： .propanoate   conjugate   oxazolidinone   asymmetric synthesis   methoxyphenyl   overall yield   amino ester   addition of lithium   epi-cytoxazone   N-benzyl methylbenzylamide   enolate oxidation   methylbenzylamino   diphosgene  

摘要： (4R,5R)-Cytoxazone has been prepared in four steps and in 61% overall yield and >98% ee. Conjugate addition of lithium (R)-N-benzyl-N-alpha-methylbenzylamide to tert-butyl (E)-3-(p-methoxyphenyl)prop-2-enoate and subsequent in situ diastereoselective enolate oxidation with (+)-(camphorsulfonyl)oxaziridine gave tert-butyl (2R, 3R, alphaR)-2-hydroxy-3-(p-methoxyphenyl)-3-(N-benzyl-N-alpha-methylbenzylamino) propanoate in >98% de. Subsequent N-benzyl deprotection to the primary beta-amino ester via hydrogenolysis, oxazolidinone formation with C(2)-retention by treatment with diphosgene and chemoselective ester reduction furnishes ( 4R, 5R)- cytoxazone. The synthesis of the C(5)- epimer, (4R,5S)-epi-cytoxazone in 44% overall yield, has also been completed via a protocol involving N-Boc protection of the primary beta-amino ester, utilization of the N-Boc group to facilitate simultaneous C(2)-inversion and oxazolidinone formation, and subsequent reduction.

关键词： Amino-Terminal Amino Acid   Aldoximes   Amino Acids   Synthons   Asymmetric synthesis   Ketoximes   Carboxyl Group   Hydroxylamines  

摘要： A new asymmetric synthesis of alpha-amino acids is described in which the key step is the highly diastereoselective addition of organolithium carboxyl synthons (2-furyllithium, phenyllithium, vinyllithium) to (R)- and (S)- O(1-phenylbutyl) oximes 2 to give hydroxylamines 3, with vinyllithium being the most satisfactory nucleophilic reagent. Subsequent reductive cleavage of the N-O bond in hydroxylamines 3, followed by N-protection, and oxidative cleavage of the carboxyl precursor gave a range of N-protected amino acids and esters. The method was exemplified by the synthesis of a range of derivatives of non-proteinogenic amino acids such as 4-bromophenylalanine, tert-leucine, norvaline, cyclohexyl- and aryl-glycines, 2-amino-8-oxodecanoic acid (Aoda) and alpha-methylvaline.

关键词： (S)-1-苯矾-2-丙醇   立体选择性还原   动力学   面包酵母  

摘要： 手性化合物的光学纯度对其生物活性具有重要影响，制备高效低毒、弱副作用的各种光学纯手性药物，需要单一对映体；光活性醇是天然产物及手性药物合成中的有用的“手性砌块”（chiral building blocks），被人们广泛用作杀虫剂及液晶材料生产的重要手性中间体，因其具有重要的应用价值，己引起人们的广泛兴趣。前手性酮的立体选择性催化还原是制备光学活性醇的一个重要方法。本文用溴丙酮与苯亚磺酸钠反应合成苯基丙酮砜，然后在面包酵母的作用下还原成（S）-苯砜-2-丙醇，（S）-苯砜-2-丙醇不仅具有抗胆甾脂的活性，而且还是一个非常有用的手性合成子。 主要合成方法有***等生物酶还原法、亚砜醇的氧化和外消旋体的脂肪酶拆分法以及水相中面包酵母还原法。使用***生物酶还原法，其化学收率较高，但其生物酶进口价格较昂贵，而且操作过程中酶容易失活，且光学收率为76％，不是很令人满意；氧化和脂肪酶拆分法则有反应路线较长、化学收率低等缺点；水相中面包酵母还原法中，面包酵母和蔗糖用量大，反应时间较长，后处理烦琐，收率不高。并且我们作了重复试验，也并未得到预期的结果。本文研究了在有机相中，用面包酵母还原苯基丙酮砜采用三水平四因素正交实验法初步确定反应的条件，并进一步研究了水含量、反应时间及水PH值等条件对此反应收率的影响，从而确立了此反应的最佳条件：反应置于恒温摇床（温度35℃，120rpm），酵母加量为0.4556g,底物加量为0.0308g，溶剂用环己烷10mL，水量为0.8 mL反应结束后，用气相色谱标定此反应的收率。其化学收率达94.76％，为了测定产物的光学纯度，对其进行了分离，其分离收率达86.56％,光学收率达100％，[α]D22.5=13.59°；同时对此反应的动力学进行了初步的研究，结果符合米氏理论，得出了此反应的最大反应速度Vm=0.04825mol／L·h，并确定了米氏常数的值，即Km=0.001338mol／L证明了在有机相中利用面包酵母催化还原苯基丙酮砜的反应可顺利行。由于产物的纯品没有商品化，为了获得气相色谱法测定收率的标准品，我们采用了化学法还原，用硼氢化钠，在甲醇中，于室温下进行还原，得到外消旋的1-苯砜-2-丙醇的纯品，并进行了结构表征。

关键词： BETA-AMINO ACIDS   INFLUENZA NEURAMINIDASE INHIBITORS   KINETIC RESOLUTION   RING-CLOSURE   CONJUGATE ADDITIONS   STRUCTURAL-ANALYSIS   AQUEOUS-SOLUTION   ALPHA   DERIVATIVES   ETHERS  

摘要： The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, > 98% d.e. and > 97% e. e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-( 3R, 4R)- and trans-( 3R, 4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-( 3R, 4R), four steps, > 98% d.e., 52% overall yield;for trans-( 3R, 4S), five steps, > 98% d.e., 50% overall yield.

关键词： alkoxides   allylations   asymmetric synthesis   iridium   P ligands  

摘要： Elimination and racemization limit the synthesis of sterically hinderedethers,such as alpha-chiral ethers,by the Willamson ***-metal-catalyzed allylic substitution could be used to prepare these materials fromachiral or racemic allylic electrophiles,but intermolecular enantioselective reactions of allylicacetates or carbonates with alkoxides are *** reactions of phenoxides are welldocumented,but no metal catalyzes intermolecular enantioselective allylations of alkoxides withbroad scope.

关键词： Friedl(a)nder缩合反应   邻氨基苯甲醛   喹啉衍生物   杂环化学   不对称合成   药物合成  

摘要： 由于Friedl(a)nder缩合反应通常是以邻氨基苯甲醛为原料与各种含α-氢的醛或酮发生缩合,其缩合反应应用于杂环化学、天然产物化学、药物化学、配位化学、金属有机化学、不对称有机合成化学等诸多研究领域.综述了国内外Friedl(a)nder缩合反应的研究进展近况.

关键词： 重点实验室   学术委员会   四川省科学技术厅   手性技术   会议  

关键词： alpha-chloroheteroarylalkyllithium   methylcyclohexanone   heteroaryloxirane  

摘要： alpha-chloroheteroarylalkyllithiums generated by deprotonation of 2-(1-chloroalkyl)-heterocycles with n-BuLi in THF at - 78 degrees C, were found to react as Darzens-type reagents with racemic and optically pure 2- and 3-methylcyclohexanones. Heteroaryloxiranes containing new stereocentres were isolated in a diastereo- and enantioselective manner.