A one-pot multistep approach to alpha-azido-phosphonate and phosphonothioate diesters: key intermediates in the synthesis of haptens for the generation of antibody ligases.

A four-step, one-pot synthesis of mixed alpha-azido-phosphonates and phosphonothioates 12a-d is described. This chemistry has provided a facile route to haptens 6a b and 7 that have been employed for the elicitation of antibody ligases. Five hapten-specific antibodies have been identified as modest catalysts of a model peptide ligation reaction between thioester 1b and thiol 2 to give the amide product 5.