Unified, Asymmetric Total Synthesis of the Asnovolins and Related Spiromeroterpenoids: A Fragment Coupling Approach.

ABSTRACT: 3,5-Dimethylorsellinic acid (DMOA)-derived spiromeroterpenoids are a unique natural product family with attractive structures, unconventional stereochemistry, and potent biological activities. Herein, we report the first asymmetric total syntheses of the asnovolins, DMOA-derived spiromeroterpenoids. The spirocyclic skeleton was efficiently assembled through a sterically hindered bis-neopentyl 1,2-addition coupling/oxidative Michael addition sequence. The unusual axial C12-methyl stereochemistry was established via metal hydrogen atom transfer (MHAT) reduction involving a chair-to-boat conformational change. The mechanism of the HAT process was studied through both deuterium labeling and computational studies. Attempted late-stage alkene isomerization of an exocyclic enone proved to

SUBMITTER: Yang F 

PROVIDER: S-EPMC9667390 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature