Two Syntheses of dl-Aplysistatin

dl-Aplysistatin (1) was synthesized by two independent routes. The first (Scheme II) proceeded in seven steps and 4% yield from homogeraniol, utilized the mercuric ion mediated brominative cyclization of diene 2 as the key transformation, but lacked stereocontrol over the relationship between C₁₂ and the A-ring stereocenters. The second synthesis (Scheme III) was achieved in eight steps and 31% yield from lactone 10, involved the aldol reaction of tert-butyl crotonate enolate anion with a single face of the aldehyde derived from hemiacetal 11, and allowed high 1,3-diastereoselectivity in the Hg(II)-induced cyclization of alcohols 20. Difference NOE spectroscopy played an important role in the deduction of stereochemistry in lactones 24.