An antibody-catalyzed allylic sulfoxide-sulfenate rearrangement

Antibodies SZ-cis-39C11 and SZ-trans-28F8, which were elicited in response to N-aryl-3-methoxyphenyl proline derivatives, catalyze the [2,3]-sigmatrop ic rearrangement of allylic sulfoxides to sulfenates. Reduction of the sulf enates with dithiothreitol in situ yields allylic alcohols as the final pro duct. The antibodies achieve rate accelerations in the range 10(2)-10(3) ov er background and exhibit distinctive hapten-dependent substrate specificit y and enantio- and diastereoselectivity. Of particular note is the effectiv e chirality transfer from the sulfoxide center to the product alcohol in th e SZ-cis-39C11-catalyzed conversion of (Z)-2-(4-methoxyphenyl)-but-2-en-1-y l 4-nitrophenyl sulfoxide. These properties can be contrasted with those of bovine serum albumin (BSA) which accelerates the same reactions to a compa rable extent but does not discriminate between substrate isomers. Partition ing of substrate from aqueous solution into the less polar environment of t he protein pocket, can account for much of the observed rate enhancement, w hereas specific conformational constraints programmed by the haptens must o rient the flexible substrate within the induced antibody-combining sites so as to favor certain reaction pathways over others. These studies thus expa nd the scope of antibody catalysis to an important new class of pericyclic reactions and illustrate how medium. effects can be exploited together with conformational constraint to control reactivity and selectivity.