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 α,β-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.