Studies on asymmetric total synthesis of (−)-β-hydrastine via a chiral epoxide ring-opening cascade cyclization strategy |
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| Authors: | Jihui Li Tianxiao Wu Xinjing Song Yang Zheng Jiaxin Meng Qiaohua Qin Yongxiang Liu Dongmei Zhao Maosheng Cheng |
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| Institution: | Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016 People''s Republic of China.; Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016 People''s Republic of China ; Institute of Drug Research in Medicine Capital of China, Benxi 117000 People''s Republic of China |
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| Abstract: | Herein, facile and enantioselective approaches to synthesize the core phthalide tetrahydroisoquinoline scaffold of (−)-β-hydrastine via both a CF3COOH-catalyzed (86% ee) and KHMDS-catalyzed (78% ee) epoxide ring-opening/transesterification cascade cyclization from chiral epoxide under very mild conditions are described. The key elements include a highly enantioselective epoxidation using the Shi ketone catalyst and an intramolecular CF3COOH-catalyzed cascade cyclization in one pot, and a late-stage C-3′ epimerization under MeOK/MeOH conditions as the key steps to achieve the first total synthesis of (−)-β-hydrastine (up to 81% ee).Herein, both CF3COOH-catalyzed (86% ee) and KHMDS-catalyzed (78% ee) chiral epoxide ring-opening cascade cyclization to facile and enantioselective synthesis of the core phthalide tetrahydroisoquinoline scaffold of (−)-β-hydrastine are described. |
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