Studies towards trichodimerol: Novel cascade reactions and polycyclic frameworks

Trichodimerol (1) is a synthetically attractive natural product because of its potential medical use against septic shock and its striking molecular a rchitecture. We report herein the possible biosynthetic pathway for its for mation from the hexaketide sorbicillin (3) and our preliminary results towa rds the total synthesis of trichodimerol (1) and its congener demethyltrich odimerol (2). These studies provided a way to synthesize P-ketal ketones by a novel variation of the Mukaiyama Aldol reaction, afforded new insight in to the mild and regioselective formation of silyl enol ethers, and allowed the preparation of the advanced intermediate 38. Furthermore, a number of u nprecedented cascade reactions were discovered furnishing novel polycyclic, highly oxygenated compounds from simple starting materials.