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

在1990年4月至1992年3月这项为期两年的研究中，我们成功地合成了以(-)-酒石酸(1)为起始抗肿瘤活性的抗生素(+)-阿斯匹林(4)。该战略包括6，8-二恶二环的衍生和有效利用[3.2。杂环烷骨架(3)作为一种关键中间体，具有很高的位选择性和立体选择性，可作为合成光学活性6-取代5-羟基-5，6-二氢-2-吡喃的通用方法。在酒石酸手性试剂开发项目中，0，0-二苯甲酰酒石酰亚胺(5)以3步反应高产率合成N-溴酰亚胺(6)。用N-溴酰亚胺(6)进行苯乙烯的溴醚化反应也曾尝试过，但在手性诱导方面没有成功。D-甘露醇(2)经两步反应转化为手性C2对称的吡咯烷(7)，再经短步骤转化为几种C2对称的吡咯烷(8)和D2对称的吡咯烷(9)。在二乙基锌与苯甲醛的加成反应中，考察了这些吡咯烷作为手性催化剂配体的性能，其中一种吡咯烷的手性诱导率为82%。在开发天然产物合成新试剂的研究中，我们发现了氰基甲酸乙酯/30%过氧化氢的组合体系作为一种有用的烯烃环氧化体系，该体系非常温和，适用于含有酸不稳定官能团的底物。

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.