Research for Synthetic Utilization of Easily Available C_2-Symmetric Chiral Compounds

易得C_2对称手性化合物的合成利用研究

基本信息

批准号：
02670958
负责人：
MASAKI Yukio
金额：
$ 1.34万
依托单位：
Gifu 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：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

In the research supported by this grant for two years term from April 1990 to March 1992, we have succeeded in the total synthesis of antibiotic(+)-asperlin(4)with antitumore activity staring with(-)-tartaric acid(1). The strategy included derivation to and effective utilization of 6, 8-dioxabicyclo[3.2. lloctane skeleton(3)as a key intermediate which is transformed highly site- and stereoselectively, and will serve as a general synthetic method for optically active 6-substituted 5-hydroxy-5, 6-dihydro-2-pyrones. In the project for development of chiral reagents from tartaric acid, 0, 0dibenzoyl-tartarimide(5)was syntesized in a 3-steps sequence and a high yield, and derived to the N-bromoimide(6). Bromoetherification of styrene by use of the N-bromoimide(6)was tried but unsuccessful in chiral induction. D-Mannitol(2)was transformed in a 2-steps sequence to chiral C_2-symmetric pyrrolidine(7), which was converted in short-steps sequences into several kinds of C_2-symmetric pyrrolidines(8)and D_2-symmetric ones(9). Examination of these pyrrolidines as chiral catalyst ligands was performed in the addition reaction of diethylzinc to benzaldehyde and a high chiral induction of 82% ee was attained with one of these pyrrolidines. In the research for exploitation of new reagent for natural product synthesis, we found a combination system of ethyl cyanoformate/30% hydrogen peroxide as a useful olefin-epoxidizing system which appears to be very mild and applicable to substrates bearing acid-labile functional groups.

在这项赠款支持的研究中，从1990年4月到1992年3月，我们成功地完成了抗生素（+） - 阿斯珀林（4）的总合成，其抗杀活性持有（ - ） - tart酸（1）。该策略包括对6、8-二甲状腺微环流的派生和有效利用[3.2。 lloctane骨骼（3）作为一个关键的中间体，该中间体被高度立体和立体选择性转化，并将用作光学活性6-取代的5-羟基5，6-Dihydro-2-Pyrones的一般合成方法。在tart酸的手性试剂开发项目中，以3个步骤序列和高产率合成0，0 dibenzoyl-tartarimide（5），并衍生于N-溴酰亚胺（6）。尝试通过使用N-溴酰亚胺（6）对苯乙烯进行溴醚化，但在手性诱导方面没有成功。将D-甘露醇（2）在2步序列中转化为手性C_2-对称吡咯烷（7），该吡咯烷（7）以短步骤序列转化为几种C_2-对称吡咯烷（8）和D_2-对称的吡咯烷（8）和D_2-对称 - 对称 - 对称 - 对称性（9）。研究这些吡咯烷作为手性催化剂配体的研究是在二乙基对苯甲醛的添加反应中进行的，并使用其中一种吡咯烷素获得了82％EE的高性诱导。在开发新试剂自然产物合成的研究中，我们发现了氰基甲酸乙酯/30％过氧化氢的组合系统，作为一种有用的烯烃 - 环氧化系统，该系统似乎非常温和且适用于具有酸性耐酸官能团的底物。