Shibuguchi Tomoyuki, Mihara Hisashi, Kuramochi Akiyoshi, Ohshima Takashi, Shibasaki Masakatsu
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Chem Asian J. 2007 Jun 4;2(6):794-801. doi: 10.1002/asia.200700070.
Catalytic asymmetric Michael and Mannich-type reactions of glycine Schiff bases with chiral two-center organocatalysts, tartrate-derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6-disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich-type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich-type reaction, aromatic N-Boc-protected imines (Boc = tert-butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich-type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)-nemonapride, which is an antipsychotic agent.
本文描述了甘氨酸席夫碱与手性双中心有机催化剂酒石酸衍生的二铵盐（TaDiASs）的催化不对称迈克尔反应和曼尼希型反应。基于构象研究，新设计了具有2,6-二取代环己烷螺缩醛的优化TaDiASs。这些TaDiASs催化甘氨酸席夫碱的不对称迈克尔反应和曼尼希型反应，对映选择性高于先前的催化剂。在曼尼希型反应中，芳香族N - Boc保护的亚胺（Boc = 叔丁氧羰基）以及可烯醇化的烷基亚胺均可适用。作为使用优化的TaDiASs进行催化不对称曼尼希型反应的合成应用，我们开发了抗精神病药物（+）-奈莫必利的催化不对称全合成。
