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

在1990年4月至1992年3月的两年研究中，我们成功地从（-）-酒石酸（1）出发，全合成了具有抗肿瘤活性的抗生素（+）-asperlin（4）。该策略包括6，8-二氧杂双环[3.2]的衍生和有效利用。辛烷骨架（3）作为关键中间体，具有高度的位置选择性和立体选择性，有望成为光学活性6-取代-5-羟基-5，6-二氢-2-吡喃酮类化合物的通用合成方法。以酒石酸为原料，经三步反应合成了0，0-二苯甲酰基酒石酸酰亚胺（5），并得到N-溴代酰亚胺（6）。尝试了使用N-溴酰亚胺（6）对苯乙烯进行溴醚化，但在手性诱导方面不成功。D-甘露醇（2）经两步转化为手性C_2对称吡咯烷（7），后者经短步转化为几种C_2对称吡咯烷（8）和D_2对称吡咯烷（9）。这些吡咯烷作为手性催化剂配体的检查进行了二乙基锌苯甲醛的加成反应，并获得了82%ee的高手性诱导与这些吡咯烷之一。在开发天然产物合成新试剂的研究中，我们发现氰基甲酸乙酯/30%过氧化氢的组合体系是一种有效的烯烃环氧化体系，它非常温和，适用于含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.