Formation of Bridge-Methylated Decalins by Antibody-Catalyzed Tandem Cationic Cyclization

Abstract

We report the antibody catalysis of an electrophilic tandem ring forming process that yields a bicyclic ring system at neutral pH. Three closely related decalin systems that represent rings A and B of the steroid nucleus account for 50% of the overall products. The linear diene substrate has been designed to mimic the first two isoprene units of 2,3-oxidosqualene, where the epoxide oxygen has been substituted by an arylsulfonate as leaving group. The hapten is based on a decahydroquinoline system with an N-oxide functionality as the key structure to elicit a combining site architecture capable of promoting leaving group release. The kcat for the formation of sulfonic acid in the catalyzed reaction was determined to be 0.021 min-1. The efficiency of the antibody-catalyzed process is underscored by the fact that the bicyclic products are not formed in the absence of the antibody catalyst under our mild conditions.