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

• Published in: Journal of organic chemistry Vol. 61; no. 1; pp. 125 - 132
• Main Authors: Anderson, Glen T, Alexander, Michael D, Taylor, Scott D, Smithrud, David B, Benkovic, Stephen J, Weinreb, Steven M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.01.1996; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ALCOHOLS; ORGANIC-SYNTHESIS; MODIFIED CURTIUS REACTION; ACIDS; SPONGE CRAMBE-CRAMBE; CRAMBESCIDINS; CONVENIENT REAGENT
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo951469t

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.