Catalytic Antibodies in Synthesis: Design and Synthesis of a Hapten for Application to the Preparation of a Scalemic Pyrrolidine Ring Synthon for Ptilomycalin A

Abstract

A catalytic antibody-based approach toward the synthesis of an optically active pyrrolidine ring synthon potentially useful for ptilomycalin A is described. Enantiomerically pure hapten 37 was designed and constructed with the eventual goal of generating antibodies for the enantioselective partial hydrolysis of a meso diester such as 44 into a monoacid 45. This transition state analog possesses a phosphonate group containing the requisite oxyanionic character of the tetrahedral intermediate for ester hydrolysis. A newly developed carbamate-based linker, which was found to be much more hydrolytically stable than the commonly used glutarate ester, was developed for coupling of the hapten to a carrier protein.