Enantioselective Total Synthesis of (+)-Nordasycarpidone, (+)-Dasycarpidone, and (+)-Uleine

The structure of uleine type alkaloids is characterized by the presence of a bridged tetracyclic hexahydro-1H-1,5-methanoazocino[4,3-b]indole ring system 1. Various strategies have been developed to access this polycyclic structural motif. We report herein a one-step conversion of appropriately functionalized 1,3,4-trisubstituted cyclopent-1-ene to 1 by way of an integrated oxidation/reduction/cyclization (iORC) process. This domino sequence, initiated by oxidative cleavage of cyclopentene ring, generated subsequently a cyclohexenone, an indole and a 1,3-bridged piperidine ring through formation of one C-C and two C-N bonds. Compound 1 is subsequently converted to nordasycarpidone, dasycarpidone and uleine. The chirality of the molecule was introduced by enzymatic desymmetrization of commercially available meso cis-3,5-diacetoxy-1-cyclopentene.

Automated summary

A one-step conversion process was developed to transform appropriately functionalized 1,3,4-trisubstituted cyclopent-1-ene into uleine type alkaloids through an integrated oxidation/reduction/cyclization (iORC) pathway, forming a diverse ring system and introducing chirality.