FORMATION OF BRIDGE-METHYLATED DECALINS BY ANTIBODY-CATALYZED TANDEM CATIONIC CYCLIZATION

We report the antibody catalysis of an electrophilic tandem ring formi ng process that yields a bicyclic ring system at neutral pH. Three clo sely related decalin systems that represent rings A and B of the stero id nucleus account for 50% of the overall products. The linear diene s ubstrate has been designed to mimic the first two isoprene units of 2, 3-oxidosqualene, where the epoxide oxygen has been substituted by an a rylsulfonate as leaving group. The hapten is based on a decahydroquino line system with an N-oxide functionality as the key structure to elic it a combining site architecture capable of promoting leaving group re lease. The k(cat) for the formation of sulfonic acid in the catalyzed reaction was determined to be 0.021 min(-1). The efficiency of the ant ibody-catalyzed process is underscored by the fact that the bicyclic p roducts are not formed in the absence of the antibody catalyst under o ur mild conditions.