Synthesis of phosphinopeptides via the Mannich ligation

Phosphinopeptides are a class of unnatural peptides containing a tetrahedral phosphorus atom and have potential for use as enzyme inhibitors. A series of phosphinopeptides were synthesized via the Mannich-type reaction of aryldichlorophosphines, aldehydes, and N-protected amino amides or peptide amides and subsequent aminolysis with amino esters or peptide esters. The current method named the Mannich ligation is an efficient route to synthesis of phosphinopeptides through convergent condensation.