Synthetic efforts toward the framework of rhynchines A–E

Abstract

We designed and attempted the collective total synthesis of rhynchines A–E, successfully developing a rapid method for constructing their chiral tetracyclic core framework. Starting from commercially available amino acid, we achieved the target 6/5/7/5 tetracyclic framework through three sequential steps: reductive amination, ester hydrolysis, and Friedel-Crafts acylation. After unsuccessful attempts at α-ethylation of the amide, we successfully constructed ethyl-substituted 6/5/7/5 tetracyclic compounds by introducing the ethyl group prior to five-membered lactam formation through a three-step sequence.