半胱氨酸合酶的功能与合成应用研究进展

在植物和细菌中,半胱氨酸合酶是L-半胱氨酸合成的关键酶,催化O-取代-L-丝氨酸与硫化氢合成L-半胱氨酸.除了参与L-半胱氨酸的合成与调控,近年来研究发现半胱氨酸合酶还参与维持胞内硫稳态、氧化还原平衡调控、细菌接触生长抑制、抗宿主氧化防御等生理活动.作为一种重要天然合成酶,半胱氨酸合酶因高度立体选择性和催化多功能性,应...     

添加剂对脂肪酶促酮基布洛芬立体选择性酯化反应的影响

探讨了添加剂对脂肪酶Ｎｏｖｏｚｙｍ４３５催化酮基布洛芬立体选择酯化反应的影响。极性助溶剂苯、甲苯的添加有利于提高酶反应的对映体选择性;此外,添加少量冠醚,即能提高酯化反应速度又能提高酶反应的对映体选择,而Ｎ,Ｎ－二甲基甲酰胺的添加不利于酶反应对映体选择性的提高。     

立体选择性合成异喹啉生物碱的最新进展

综述了立体生合成异喹啉生物碱的一些最新进展、其中和传统合成方法改进的立体选择性合成如Ｐｉｃｔｅｔ－Ｓｐｅｎｇｌｅｒ缩合，Ｐｏｍｅｒａｎｚ－Ｆｒｉｔｓｃｈ环合和Ｂｉｓｃｈｌｅｒ－Ｎａｐｉｅｒａｌｓｋ对映选择性还原等以及用现代的Ｃ－Ｃ联接策略进行的立体选择性合成方法。     

发面酵母在制备手性合成结构块中的应用（下）碳碳键形成及其它反应

发面酵母方便易得，不仅能催化羰基和碳碳双键不对称还原，而且能催化碳碳键形成反应和其它各种各样的立体选择性反应，在制备双或多官能团手性合成结构方面应用广泛。其中某些生物催化反应类型最近首见报道。     

α-生育酚琥珀酸酯的酶法合成研究进展

酶法合成具有反应条件温和、选择性高及环境友好等特点,为制备高质量的α-生育酚琥珀酸酯提供了一条新途径.本文首先概述了酶法合成α-生育酚琥珀酸酯的催化剂及其催化机制,重点介绍了酶催化合成α-生育酚琥珀酸酯的研究成果,讨论了酶催化合成α-生育酚琥珀酸酯研究中的若干问题,最后展望了酶催化合成α-生育酚琥珀酸酯的发展前景.     

(-)-7-羟基-3-羰基-6-[4-苯氧基-3-羟基-1-(E)-丁烯基]-2-氧杂二环[3,3,0]辛烷合成工艺的改进

目的 改进磺前列酮中间体3(S)-烯醇化合物的合成工艺。方法 以双羟化合物为起始原料经硅醚化、选择性氧化、Wittig-Homer反应、水解及立体还原得到3(S)-烯醇化合物。结果 制备得到目标化合物，总收率11％。结论 改进后的合成方法操作简便、易于掌握、反应条件温和、更加适合工业化生产。     

含D-氨基酸残基多肽的酶促合成

本文介绍了含D-氨基酸残基多肽的酶促合成方法:动力学控制酶反应和非水介质中进行的酶反应.在非水介质中,不仅可以改变蛋白酶的立体选择性,而且使酯酶成为含D-氨基酸残基多肽的合成酶.本文阐述了这两种方法的机理,并列举了一些含D-氨基酸残基多肽酶促合成的例子.     

倍他洛尔两种对映体的化学酶催化拆分法

利用脂酶催化拆分公胺基醇的方法，可以对外消旋的倍他洛尔或其中间体1-氯-3－［4-（2-环丙基甲氧基）乙基〕苯氧基丙-2-醉（1）进行拆分。前法是在合成外消旋倍他洛尔后，将它和乙酸盯在吡啶中进行N，O-双乙酸化，再在酶催化条件下选择性水解，实验证明只有PPL和K－10这两种酶具有拆分活性，对映体选择性系数E值分别为5和1．so提高反应体系的乳化程度对酶的E值天明显改善。后法是利用乙酸乙烯酯作为乙酸基供给体，在酶催化条件下，对五的混旋体进行选择性的酯交换反应，再分别胺化、水解，得到倍他洛尔的s型和R型对映体。在所用酶中，S…     

多非利特的合成

2—(4—硝基苯基)乙胺经两次N—烷基化反应、催化加氢还原和甲磺酰化制得抗心律失常药多非利特。具有合成步骤短、反应条件温和及选择性好等优点。总收率46．5％。     

金催化甘露糖-b-(1→6)-甘露糖-b-(1→6)-葡萄糖三糖的合成

目的 利用金催化立体选择性构建b-甘露糖苷键的方法高效合成甘露糖-b-(1→6)-甘露糖-b-(1→6)-葡萄糖三糖。方法 以4,6-O-苄叉保护的甘露糖邻己炔基苯甲酸酯3为供体,在Au(I) 复合物和银盐催化下,与葡萄糖受体4反应,得到二糖产物5;二糖5在Bu₂BOTf/BH_3.THF条件下,将苄叉选择性还原开环至6-羟基,得到二糖受体6,进而再与糖基供体3反应,得到三糖2。 结果 分别以90%的产率、b/a = 14.2/1的选择性得到二糖5和88%的产率、b/a = 15.9/1的选择性得到三糖2。     

聚合物固载试剂在手性药物合成中应用的研究进展

当前手性药物合成的研究已成为国际药学研究领域的热点之一,近几年发展起来的在聚合物固载试剂条件下进行的不对称合成由于其各种优点,引起了药学界广泛的关注.无论从经济角度还是从“绿色化学”角度考虑,聚合物固载试剂的巨大潜力势必会推动手性药物合成技术的迅速发展.从抗肿瘤类、抗生素类、天然产物类和生物化学类活性物质对近几年来聚合物固载试剂在手性药物合成方面的应用进行简述,并对其前景进行展望.     

手性叔丁基亚磺酰胺的制备方法及其在药物合成中的应用

手性叔丁基亚磺酰胺是近年来发展起来的一种新型医药中间体,也是合成手性胺类药物及其中间体的关键手性源,其相关研究受到研究人员的广泛关注。综述手性叔丁基亚磺酰胺的制备方法以及该化合物在药物合成领域中的应用情况。     

不对称烷基化反应在药物及生物活性化合物 合成中的应用

该文从合成光学活性化合物的3种手性诱导方式——手性源诱导的不对称反应、手性助剂诱导的不对称反应及不对称催化反应来介绍近年来不对称烷基化反应在药物及生物活性化合物合成中的应用。     

催化不对称合成法在手性药物合成中的应用

结合实例就催化不对称合成的两种方法应用于手性药物合成作简要概述。外消旋体拆分、化学计量不对称合成和催化不对称合成是利用化学手段获得手性药物的 3种方法 ,其中催化不对称合成法是最经济有效地合成手性药物的方法 ,它又可分为化学催化不对称合成法和酶催化不对称法。     

新型手性配体的合成及其在沙美特罗关键中间体合成中的应用

目的合成沙美特罗的关键手性中间体。方法设计合成新型手性配体单磺酰化1，2-双-（3，5-二甲基苯基）乙二胺，通过与金属铑配合生成手性催化剂，利用该催化剂催化沙美特罗的关键手性中间体的不对称氢转移反应。结果与结论新型手性配体具有良好的催化活性和对映体选择性，催化合成得到的沙美特罗中间体的对映体选择性的ee％值为91％。     

转氨酶在手性化合物合成中的研究进展

目的总结近几年国内外转氨酶在手性化合物合成中的研究进展,主要包括转氨酶蛋白工程、转氨酶表达与固定化、转氨酶过程工程以及转氨酶应用。方法检索近几年国内外转氨酶相关文献共56篇,从转氨酶蛋白工程、表达与固定化、过程工程及应用方面进行归纳总结。结果近几年,转氨酶蛋白工程是国内外的研究热点,利用蛋白工程对转氨酶进行改造是开发新酶的有力手段;国内外多采用原核表达系统进行转氨酶的表达,且固定化转氨酶应用较多;转氨酶过程工程研究发现可通过加入过量氨基供体、移除副产物、酶偶联反应等手段突破反应瓶颈;转氨酶主要用于手性胺、手性氨基酸、手性氨基醇及重氢标记的手性胺的合成,且一些转氨酶已经用于工业化高效生产手性胺,但能用于工业生产的转氨酶数量较少。结论转氨酶已经迅速发展为有价值、有竞争力的生物催化剂,研究转氨酶对于医药及化工领域手性胺的高效、绿色合成具有重大意义。     

Efficient chiral control based on five-membered heterocyclic and related systems

The synthetic potential of some simple five-membered heterocycles, including 2-oxazolone, 1,3-dihydro-2-imidazolone and 2-thiazolone as building blocks for chiral polyfunctional compounds as well as chiral heterocyclic auxiliaries for asymmetric synthesis is reviewed. The stereodefined introduction of easily replaceable groups to the 4,5-olefinic moiety of the 2-oxazolone ring to give versatile chiral synthons, followed by stereospecific and stepwise substitution, provides a working and versatile strategy for achieving a chiral synthesis, which leads to the preparation of a wide variety of 2-amino alcohols of biological interest. Sterically constrained chiral 2-oxazolidinones and the derived conformationally rigid amino alcohols, which are derived from cycloaddition reactions of the 2-oxazolone to cyclic dienes such as 9,10-dimethylanthracene and hexamethylcyclopentadiene, represent excellent chiral auxiliaries and chiral ligands which are of general use in asymmetric synthesis. The strategy developed using 2-oxazolone can also be used in the cases of the structurally similar 1,3-dihydro-2-imidazolone and 2-thiazolone derivatives.     

The use of microbial and enzymatic function in organic synthesis. Total synthesis of the aglycone of venturicidins A and B

The synthesis of chiral synthons by means of microbial and enzymatic function and its application to the synthesis of complex, bioactive substances, the aglycone of venturicidins A and B are reviewed. 1) The syntheses of chiral synthons having two chiral centers are described based on the microbial asymmetric reduction of alpha-methyl beta-keto esters or enzymatic asymmetric hydrolysis of alpha-methyl beta-acetoxy esters. 2) The new chiral synthons synthesized in 1) have been successfully applied for the total syntheses of oudemansins A and B. 3) Purification and properties of the asymmetric reduction enzyme of alpha-methyl beta-keto esters in Saccharomyces cerevisiae or Saccharomyces fermentati were investigated. 4) Formal total synthesis of (-)-indolmycin is described based on the asymmetric hydrolysis of alpha-acetoxy ester with lipases. 5) Enzymatic hydrolysis in organic solvents for kinetic resolution of water-insoluble alpha-acyloxy esters with immobilized lipases is described. 6) The first total synthesis of the aglycone of venturicidins A and B has been successfully achieved from the new chiral synthon based on the developed method in 1).     

Synthesis and its application to the synthesis of biologically active natural products of new and versatile chiral building blocks

This article describes a design and synthesis of new and versatile chiral building blocks and its application to the biologically active natural product synthesis. The chiral building blocks were prepared using a biocatalysis in an enantiomerically pure state. As an application of the above chiral building blocks to the synthesis of biologically active natural product, we demonstrated the diastereodivergent synthesis of the 3-piperidinol alkaloids cassine, spectaline, prosafrinine, iso-6-cassine, prosophylline, prosopinine, and also established the flexible route to the 5,8-disubstituted indolizidine or 1,4-disubstituted quinolizidine type of Dendrobates alkaloids. As another application to the synthesis of biologically active alkaloids, we accomplished the first enantioselective total synthesis of marine alkaloids clavepictines A, B, and pictamine using a highly stereoselective Michael type quinolizidine ring closure reaction as the crucial step, and the first total synthesis of a marine alkaloid lepadin B was also achieved using aldol cyclization controlled by a A strain.     

Asymmetric intramolecular conjugate addition of chiral enolates via non-equilibrium

Optically active alpha,alpha-disubstituted alpha-amino acids belong to an important class of unnatural amino acids. Since the synthesis of such amino acids involves the creation of a quaternary stereocenter, methods for their synthesis have been extensively studied. We have reported that N-t-butoxycarbonyl(Boc)-N-methoxymethyl(MOM)-amino acid derivatives undergo asymmetric alpha-alkylation in up to 93% ee. Original chiral information on an amino acid is preserved in axially chiral enolate intermediates, and thus asymmetric induction is achieved without the aid of external chiral sources (i.e., memory of chirality). Recently, we have reported a new protocol for the asymmetric cyclization of amino acid derivatives, which enables straightforward synthesis of cyclic amino acids with a tetrasubstituted carbon center from the usual alpha-amino acids in up to 98% ee. Here we report the asymmetric construction of highly substituted chiral nitrogen heterocycles via intramolecular conjugate addition of chiral enolates generated from N-Boc-N-alkylylamino acid derivatives. This method is applicable to the asymmetric construction of pyrrolidine, piperidine, tetrahydroisoquinoline, and indoline derivatives with contiguous quaternary and tertiary stereocenters.