Umemiya Shigenobu, Shinagawa Naoya, Fujimoto Aisuke, Terada Masahiro
Research and Analytical Center for Giant Molecules, Graduate School of Science, Tohoku University, 6-3 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8578, Japan.
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
JACS Au. 2025 Jul 8;5(7):3052-3057. doi: 10.1021/jacsau.5c00630. eCollection 2025 Jul 28.
The efficient and scalable synthesis of natural products, such as polyketides, has paved the way for the discovery of pharmaceuticals, saving millions of lives and improving people's health. We report the catalytic total synthesis of bastimolide A, a potent antimalarial, in 21 steps in a total yield of 15.4%, employing various catalytic reactions without using stoichiometric asymmetric reactions or excess amounts of heavy metal reagents. Our efficient and scalable synthesis can catalytically forge seven of 10 stereogenic centers in bastimolide A through chiral Brønsted acid-catalyzed enantio- and diastereoselective allylborations and Corey-Bakshi-Shibata reduction as key steps.
天然产物（如聚酮化合物）的高效且可扩展的合成方法为药物研发铺平了道路，拯救了数百万人的生命并改善了人们的健康状况。我们报道了强效抗疟药物巴斯替莫利德A的催化全合成，该合成以21步反应完成，总产率为15.4%，采用了各种催化反应，无需使用化学计量的不对称反应或过量的重金属试剂。我们高效且可扩展的合成方法能够通过手性布朗斯特酸催化的对映和非对映选择性烯丙基硼化反应以及Corey-Bakshi-Shibata还原反应作为关键步骤，催化构建巴斯替莫利德A中10个立体中心中的7个。
