THE CHEMISTRY OF PHOSPHAPEPTIDES - INVESTIGATIONS ON THE SYNTHESIS OF PHOSPHONAMIDATE, PHOSPHONATE, AND PHOSPHINATE ANALOGS OF GLUTAMYL-GAMMA-GLUTAMATE

The synthesis of the phosphonamidate, 1d, and phosphonate, 1e, analogues of a gamma-glutamyl peptide are reported. Michaelis-Arbuzov reaction with the alkyl halide, 7b, derived from L-glutamic acid, yielded dimethyl phosphonate, 8b. Selective aminolysis of the phosphorus diester provided monomethyl phosphonic acid, 9. Utilizing the methodology developed in the accompanying paper, 9 was converted to the phosphonochloridate, 10. Subsequent reaction with diethyl glutamic acid and hydrogenation afforded the complex phosphonamidate, 1d. Mitsunobu coupling of the monomethyl phosphonic acid, 9, with diethyl 2-hydroxyglutarate, followed by hydrogenation, provided the complex mixed phosphonate, 1e.