Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one

• Published in: Angewandte Chemie Vol. 132; no. 45; pp. 20091 - 20095
• Main Authors: Xu, Ze‐Jun, Zong, Yan, Qiao, Ya‐Nan, Zhang, Jiao‐Zhen, Liu, Xuyuan, Zhu, Ming‐Zhu, Xu, Yuliang, Zheng, Hongbo, Fang, Liyuan, Wang, Xiao‐ning, Lou, Hong‐Xiang
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 02.11.2020
• Subjects: asymmetric synthesis; Chemistry; cyclization; Cyclopropane; Diterpenes; Divergence; natural products; Protonation; terpenoids; total synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202009128

A divergent synthetic approach to biogenetically related diterpenoids such as ent‐kauranes, ent‐trachylobanes, ent‐beyerane, and ent‐atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]‐octane moiety of ent‐kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.02,7]‐tricyclic core of ent‐trachylobane and regioselective cyclopropane fragmentation furnishing ent‐beyerane and ent‐atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol. The De Mayo reaction was employed to fuse the bicyclo[3.2.1]‐octane moiety of ent‐kaurane. Divergent synthesis furnishing ent‐trachylobanes, ent‐beyerane, and ent‐atisane was achieved through nucleophilic cyclopropanation and regioselective cyclopropane fragmentations.