Stereoselective Syntheses of Soman Analog

摘要

The subject of catalytic antibodies has attracted a great deal of attentionbecause of their capability of catalyzing a variety of chemical transformations. These antibodies can be generated against almost any target molecule of interest, however, the design of the hapten is the most critical part. The four stereoisomers of soman differ in toxicity, rate of inhibition of cholinesterases, response to reactivators and rate of detoxification in the body. From the viewpoint of neutralizing soman by use of an antibody it is of value to synthesize antibodies against each pure stereoisomer. This can be accomplished using a soman simulant. We report a detailed study on the synthesis, isolation and characterization of the four pure enantiomers of ((S or R-4-amino-2,2-dimethyl-2-butyl)(methyl)methylphosphonates which were conjugated to protein carriers for use in the development of potentially therapeutic antibodies that are cross-reactive with soman. A further goal is to determine whether monoclonal antibodies generated against each pure simulant stereoisomer behave selectively in catalyzing ester hydrolysis.