Total synthesis of Class II and Class III Galbulimima Alkaloids

Abstract

I. Total Synthesis of All Class III Galbulimima Alkaloids We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13, (-)-himgaline anad (-)-himbadine. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the Cl 6-carbonyl as an N-vinyl carbamate for late stage unveiling in the form of the necessary C16-enone. A vinyl-radical cyclization secured the C-ring while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection. II. Total Synthesis of (-)-Himandrine We describe the first total synthesis of (-)-himandrine, a member of the class II galbulimima alkaloids. Noteworthy features of this chemistry include a diastereoselective Diels- Alder reaction in the rapid synthesis of the tricycle ABC-ring system in enantiomerically enriched form, the use of a formal [3+3] annulation strategy to secure the CDE-ring system with complete diastereoselection, and successful implementation of our biogenetically inspired oxidative spirocyclization of an advanced intermediate. The successful and direct late-stage formation of the F-ring in the hexacyclic core of himandrine drew on the power of biogenetic considerations and fully utilized the inherent chemistry of a plausible biosynthetic intermediate.