Securinega alkaloids are an important class of bridged tetracyclic natural products distributed among plants of the Euphorbiaceae family. These plants have a rich history in traditional Chinese medicine and the Securinega alkaloids themselves have been associated with a range of biological activities. Virosaine A, isolated in 2012, contains the most highly caged skeleton of all the Securinega alkaloids. We report here a concise total synthesis of (-)-virosaine A. The synthesis is enabled by an efficient cascade reaction sequence to access the core of the natural product from a tricyclic precursor that is accessible from furan and 2-bromoacrolein in only 4 steps. In the cascade event, a Brønsted acid-initiated nucleophilic opening of an epoxide with a pendant oxime generates a nitrone that undergoes a facile [3+2] cycloaddition to give the polycyclic core in excellent yield. Late-stage C-H functionalization of the polycyclic core via a directed metalation enables the elaboration of the cascade product to (-)-virosaine A.

Total synthesis of (-)-virosaine A

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.