关键词： 多羟基-α-氨基酸   不对称合成   樟脑   三环亚胺内酯   糖醛反应  

摘要： 多羟基-α-氨基酸是一类重要的氨基酸，它们不仅本身具有很多重要的生物活性，而且是很多具有生物活性的复杂天然产物的重要结构片段。多羟基-α-氨基酸也经常作为中间体来合成其它化合物，如：polyoxins，sphingofungins等。因此，对于不对称合成多羟基-α-氨基酸的方法学研究具有基础性和应用性的双重意义。\n 从天然樟脑出发，经过4步反应，高产率(总产率大于50％)合成了三环亚胺内酯。该模板利用天然樟脑的刚性骨架，以及亚胺内酯环特殊的船式结构来达到控制aldol反应的立体选择性，经过优化条件，将三环亚胺内酯与各种糖醛反应，以很好的产率和非对映立体选择性地(＞98de)得到了一系列多羟基-α-氨基酸衍生物。该aldol反应的加成产物经水解后高产率地得到光学纯多羟基-α-氨基酸。\n 接着，将手性三环亚胺内酯应用到天然产物(+)-Conagenin的不对称全合成之中。天然产物(+)-Conagenin是从Streptomycesroseosporus发酵汤中分离出一种结构独特，生物上有重要意义的二级代谢物。这种化合物作为一种低分子量的免疫调节剂能够刺激有活性的T细胞，同时还发现它对癌症的化学疗法有很好的功效。在结构上，天然产物(+)-Conagenin包含三个紧邻的手性中心和一个含有季碳的(S)-甲基-丝氨酸片断。结合本实验室在合成α-氨基酸方面的经验，提出了一条简便可行，目前路线最短的方案，从三环亚胺内酯出发经4步高选择性，高产率的得到所需的(S)-甲基-丝氨酸甲酯。

关键词： Pyrrolidines   Aldehydes   Enantioselective synthesis   Organophosphorus compounds   Hydrogenation  

摘要： The Horner-Wadsworth-Emmons reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates represents a new method for the asymmetric synthesis of ring-functionalized cis-2,5-disubstituted 3-oxo pyrrolidines.

关键词： alpha-substituted serine   lipase-catalyzed   desymmetrization   2-nitropropane-1,3-diols  

摘要： A new approach to the asymmetric synthesis of alpha-substiluted serine analogues was developed. The method utilizes a lipase-catalyzed esterification desymmetrization protocol. In the presence of PPL, a series of benzyl-substituted quaternary 2-nitropropane-1,3-diols were successfully desymmetrized by selective acetylation in very good yields and enantioselectivities (up to 95% ee).

关键词： pyrrolidines   2-pyrrolidinones   beta-hydroxy-gamma-amino acids   N-acyliminium   piperidines   2-piperidinones   alpha-amidoalkylation   sulfones   sulfides   samarium diiodide   N-alpha-carbanion   isoindolin-1-ones   tetramic acids   tetramates   alkaloids   synthons   building blocks   Umpolung  

摘要： This account describes our recent studies on the development of chiral nonracemic cyclic imide-based synthetic methodology and the complementary N-alpha-carbanion synthon-based synthetic methodology for the asymmetric syntheses of naturally occurring or pharmaceutically interesting hydroxylated pyrrolidines, 2-pyrrolidinones, (beta-hydroxy-gamma-amino acids, and their higher homologous;as well as isoindolin-1-ones;tetramic acid and tetramate derivatives.

关键词： antithrombotic agent   M55529   cyclic N,O-acetal   enantioselective acetal formation  

摘要： The first asymmetric synthesis of antithrombotic agent M55529 is reported, wherein the first enantioselective cyclic N,O-acetal formation is clarified. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

关键词： Alcohols   Anions   Cyclization   Enantioselective synthesis   Lewis acids  

摘要： Asymmetric synthesis of the spirocyclic CID-ring moiety of (+)-ophiobolin A is described. Fragment A, which was prepared via pig liver esterase (PLE)-mediated kinetic resolution, and fragment B, which was prepared via diastereoselective allylation and subsequent kinetic iodolactonization, were coupled to afford the allylsilane 2, which was successfully cyclized to the desired spirocyclic CD-ring moiety la in the presence of a Lewis acid.

关键词： STEREOSELECTIVE-SYNTHESIS   (-)-VERTINOLIDE   REDUCTION   PRECURSOR   ALDEHYDES   LACTONES   KETONES   tetronic acid   esters   Ketones   aldehydes   Optical activity   Stereoselective synthesis   Lactones   Asymmetric synthesis   Hydration   METHYL PROPIOLATE   precursors   acids  

摘要： The optically active gamma-hydroxy-alpha,beta-acetylenic esters are obtained from the enantioselective reaction of methyl propiolate with both aliphatic and aromatic aldehydes. These compounds can undergo regiospecific hydration in the presence of Zeise's dimer, [PtCl2(C2H4)](2), to generate the optically active tetronic acids.

关键词： CATALYSIS   ORGANIC synthesis (Chemistry)   KETONES   IODIDES   AMINES   CATALYSTS   RING formation (Chemistry)  

摘要： A significant new and efficient catalytic asymmetric approach for the highly enantioselective synthesis of chiral phthalides by SmI2-induced reductive cyclization of 2-acylarylcarbonylates was developed. The combination of (4S,5R)-4,5-diphenyloxazolidin-2-one and 2,2,6,6-tetramethylpiperidine was found to be a very effective catalyst system in the reaction. This method provides a ready access to a broad range of enantiomerically enriched phthalides (up to 99% ee).

关键词： cascarillic acid   cyclopropane   aldol   retro-aldol   temporary stereocentre  

摘要： An efficient six-step asymmetric synthesis of the cyclopropane containing natural product cascarillic acid in 41% overall yield is described. The key synthetic steps involve the use of a temporary stereogenic hydroxyl group to control the facial selectivity of a directed cyclopropanation reaction and its subsequent removal via a retro-aldol reaction.

关键词： 非天然氨基酸   手性助剂   不对称合成   a-氨基酸   糠醛  

摘要： 氨基酸的不对称合成，自1968年Kagan等首先报道了L-Asp的不对称合成以来，氨基酸的不对称合成方法引起了广泛关注，不对称相转移催化法、不对称催化还原法、酶促合成等都是合成光学活性氨基酸的良好方法，这些方法具有催化剂用量少、产物e.e.值高等特点，但对于含有两个以上手性中心的目标产物而言，较难得到目标产物的所有立体异构体。较为引人注目的是Evans合成法，此方法是应用手性助剂控制引入基团的立体选择性而产生手性中心，具有反应高立体选择性的特征，对于含两个手性中心的a-氨基酸，可以合成其全部4个立体异构体，这是其他方法难以比拟的。Hruby等在Evans法的基础上，以手性助剂4(R/S)-苯基-噁唑烷-2-酮控制反应的立体选择性，先后设计合成了β支链且有芳香基团取代的非天然氨基酸，并基本都得到它们的四个光学异构体。所用的助剂有效的控制了反应的选择性(d.e.值高)。Davies等对Evans手性助剂进行了改造，合成了新型手性助剂4(R/S)-5，5二甲基-4-苯基-噁唑烷-2-酮，并用于许多不对称合成中，该助剂具有更好的控制反应立体选择性并易于回收的特点。\n 光学活性氨基酸是非常重要的生物活性分子，是构筑药物如肽、蛋白质和许多天然产物分子的基本结构单元，也被现代有机合成中广泛用于手性起始原料，手性助剂和手性催化剂。非天然氨基酸的不对称合成及肽类药物的设计筛选一直受到有机化学家的极大关注。探索该类化合物的高选择性、高效率和通用性合成方法是合成化学的前沿领域之一。本文在Davies和Hruby工作的基础上，以4(R/S)-5，5二甲基-4-苯基-噁唑烷-2-酮手性助剂自始至终对反应的立体选择性进行控制，设计合成β位为呋喃基取代的戊氨酸衍生物的四个光学活性异构体。\n 本文从易得原料糠醛出发，经过不对称1，4-Michael加成反应，直接叠氮化、或先溴代再进行SN2叠氮化反应产生不同构型的手性中心，再经碱性水解同时回收手性助剂、叠氮基的氢化还原、得到一系列活性中间体3-8和构象受阻的新颖手性α-氨基酸[2-氨基-3-(2-呋喃基)-戊酸]9的全部四个光学异构体，以期用于肽的合成设计并筛选出更高生物活性肽及其类似物。反应总收率10-20％，％e.e.