Convenient synthesis of phosphonodipeptides containing C-terminal α-aminoalkylphosphonic acids

Phosphonopeptides are important phosphorus analogs of natural peptides and have been widely applied as enzyme inhibitors and antibacterial agents. A series of phosphonodipeptides containing C-terminal α-aminoalkylphosphonic acids was synthesized in satisfactory to good yields conveniently from 2-(N-benzyloxycarbonylamino)alkanamides, aldehydes, and phosphorus trichloride via Mannich-type reaction and subsequent sequential hydrolysis. The reaction mechanism was proposed and verified by ³¹P NMR tracing experiments. The current method is an efficient and convenient method for preparation of phosphonopeptides containing C-terminal α-aminoalkylphosphonic acids.