Site-Specific Photochemical Desaturation Enables Divergent Syntheses of Illicium Sesquiterpenes

• Published in: Journal of the American Chemical Society 2021-03, Vol.143 (8), p.3256-3263
• Main Authors: Shen, Yang, Li, Linbin, Xiao, Xiaoxia, Yang, Sihan, Hua, Yuhui, Wang, Yinglu, Zhang, Yun-wu, Zhang, Yandong
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c00525

Desaturation of unactivated alkanes remains a challenging yet desirable strategy to make olefins. The Illicium sesquiterpenes usually possess highly oxygenated cage-like architectures, and some of them exhibit prominent neurotrophic effects. Here, we disclose a unique photochemical desaturation strategy for the efficient, highly stereocontrolled total syntheses of five Illicium sesquiterpenes from inexpensive (R)-pulegone, featuring a 13-step gram-scale synthesis of (−)-merrilactone A. The efficiency of the syntheses derives from an expedient construction of a tetracyclic framework via two annulations, a site-specific photoinduced single-step desaturation in a complex hydrocarbon system, and diverse oxygenation manipulations around the resultant olefin intermediate. This work highlights how late-stage desaturation can dramatically streamline the synthesis of complex terpenes and diverse non-natural analogues for establishing the structure–activity relationship and elucidating their molecular mechanisms of bioactivity.