Evolution of the Total Synthesis of (-)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation the Petasis-Ferrier Union/Rearrangement and Ring Closing Metathesis

摘要

An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (>1) and assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include: a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers; a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the thirteen membered macrocycle ring, employing for the first time a sterically demanding acetal; an intramolecular chemoselective acylation to access an embedded bicyclic lactone; and an efficient ring closing metathesis (RCM) reaction to generate the macrocyclic ring.