Construction of the Myrioneuron Alkaloids: A Total Synthesis of (±)-Myrioneurinol

A strategy has been developed that culminated in a stereoselective total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid myrioneurinol. The synthesis relies on three highly diastereoselective reactions, including an intramolecular chelation-controlled Michael spirocyclization of an N-Cbz-lactam titanium enolate to an alpha,beta-unsaturated ester for construction of the A/D-ring system and the attendant C5 (quaternary), C6 relative stereochemistry; a malonate enolate conjugate addition to a nitrosoalkene in order to install the appropriate functionality and establish the configuration at C7; and an intramolecular aza-Sakurai reaction to form the B-ring and the accompanying C9 and C10 stereocenters.