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 (31)P NMR tracing experiments. The current method is an efficient and convenient method for preparation of phosphonopeptides containing C-terminal α-aminoalkylphosphonic acids.