A concise, enantiospecific synthesis of the phospholipase C inhibitor (-)-hispidospermidin (1) has been achieved by approximating the architecture of a reactive intermediate that may lie on the biosynthetic pathway leading to this natural product. Two compounds derived from (R)-(+)-pulegone were joined by a highly diastereoselective carbonyl addition. A proximity-facilitated, acid-induced bicyclization of spiro[4.5]deca-1,7-diene 29 gave rise to the tetracyclic framework of 1 and was the key transformation in this synthesis.
All Science Journal Classification (ASJC) codes
- Drug Discovery
- Organic Chemistry
- Biomimetic synthesis