Total Synthesis of the Galbulimima Alkaloid (-)-GB17

摘要

The Galbulimima alkaloids are isolated from the bark of rainforest trees belonging to the Galbulimima genus that grow in regions of Northern Australia, Papua New Guinea, and Indonesia. Significant structural diversity exists within this alkaloid family, but common to all members is the presence of a piperidine ring and a trans-decalin carbocylic core (Scheme 1). Investigations into the biological activity of the Galbulimima alkaloids have focused in large part on himbacine (1): a potent muscarinic receptor antagonist that might serve as a lead for the development of therapeutic agents to treat Alzheimer's disease.' Himbacine-centered research at Schering-Plough led to SCH 530348 (now Vor-apaxar at Merck),''*' a promising thrombin receptor agonist. However, the clinical trial of SCH 530348 for the treatment of acute coronary syndrome was halted in 2011 owing to adverse side-effects.