Umihara Hirotatsu, Yokoshima Satoshi, Inoue Masayuki, Fukuyama Tohru
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8601, Japan.
Chemistry. 2017 May 23;23(29):6993-6995. doi: 10.1002/chem.201701438. Epub 2017 Apr 25.
Asymmetric total synthesis of (-)-morphine has been accomplished in 18 steps from commercially available 7-methoxy-2-tetralone. Our synthesis features a simple transformation from a readily prepared chiral intermediate, construction of the E-ring by acid-mediated cyclization, and singlet oxygen-mediated manipulation of the C-ring. Transformation of the final stage involves construction of the morphinan skeleton by means of 1,6-addition of in situ generated secondary amine.
以市售的7-甲氧基-2-四氢萘酮为原料，经18步反应完成了(-)-吗啡的不对称全合成。我们的合成方法具有以下特点：从易于制备的手性中间体进行简单转化、通过酸介导的环化反应构建E环以及单线态氧介导的C环操作。最后阶段的转化涉及通过原位生成的仲胺进行1,6-加成来构建吗啡喃骨架。
