Origination of functional chiral building blocks using asymmetric acylation and application to the synthesis of biologically active compounds

利用不对称酰化衍生功能性手性构件及其在生物活性化合物合成中的应用

基本信息

批准号：
05671743
负责人：
TAKAHATA Hiroki
金额：
$ 1.22万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

Enzymes are now recognized as substrate-specific and highly enantioselective catalyst for asymmetric synthesis. In particular, lipases have recently been used for biocatalytic resolutions on the basis of the admission of organic solvents as reaction media.We succeeded immobilized lipase-mediated resolution of N,N-dialky1-3-hydroxy-4-pentenamides, unsuccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation. Iodolactonizaion of thus prepared homochiral amides and oxy-lactonization of O-protected homochiral amides proceeded stereoselectively, affording both enantiomers of cis-3,4-disubstituted gamma-lactone and both enantiomers of trans-3,4, disubstituted gamma-lactone preferentially, respectively.These gamma-lactones have been used as chiral building blocks for the synthesis of biological active compounds such as litsenolides, (+) -blastimycinone, NFX-2, NFX-4, metabolites from Gorgonian Plexaura flava, and muscarine.Especially, cis-3,4-disubstituted gamma-lactones were served as the masked butenolide chirons and a concise synthesis of (+) -trans-wisky and (+) -trans-cognac lactones, (-) -methylenolactocin, (+) -nephrosteranic acid, and (+) -roccellaric acid has been achieved.In addition, these gamma-lactones have been apllied as chiral carbon five building blocks for the synthesis of insect pheromons.

现在，酶被认为是非对称合成的底物特异性和高度对映选择性催化剂。特别是，脂肪酶最近已被用作有机溶剂作为反应培养基，用于生物催化分辨率。我们成功地固定的脂肪酶介导的N，N-二硅基1-3-羟基-4-羟基-4-戊二酰胺，通过分辨率不成功，通过n-dialky1-3-羟基含量分辨率。 Katsuki-Sharpers不对称的环氧化。因此，iodolactonizaiz iodolactonizaiza iodolactonizaiz酰胺和o蛋白膜的同型同型酰胺的氧层析作用进行了立体选择性，可为Cis-3,4-脱亚成的γ-内乳酮的两个对映异构体提供，两种对照组的对照组和两种映异构体的两个对照组，以及trans-3,4这些γ-内酯已被用作手性构建块，用于合成生物活性化合物，例如litsenolides，（+） - 碱性霉菌酮，NFX-2，NFX-4，来自Gorgonian Plexaura flava的代谢物，尤其是CIS-杂物。 3,4二取代的伽马 - 内酯作为掩盖的丁烯酸奶酪和（+） - trans-wisky和（+） - - trans-cognac lactones，（（ - ） - 甲基苯甲酰基蛋白，（+） - 氯糖酸， - 硝基酸，（+） - 含量 - 氯酸， - 氯酸， - 氯糖酸，（+） - 含量 - 甲基酸， - 氯糖酸，（+） - 而且，已经实现了 - 肉眼酸。此外，这些γ-内酯被称为手性碳五个基础，用于合成昆虫信息素。