s-cis,s-trans Isomerism about the Ala-Pro peptide bond in Nα-phospho- and Nα-phosphono-l-alanyl-l-prolines by 31P n.m.r.

Nα-(Phenethylphosphono)-l -alanyl-l -proline 1, a potent inhibitor of angiotensin converting enzyme, exhibits two ³¹P n.m.r. resonances (intensity ratio one to one), which exchange with a constant (k₁) of about 1 s^?1 and a free energy of activation ΔG*=～ 20kcal/mol at 23° in deuterated dimethylsulfoxide. Two resonances in exchange are also observed in deuterium oxide at pH 7.5. Thus the exchanging ³¹P resonances report the s-cis, s-trans conformational equilibrium about the alanyl-proline peptide bond. Similar results were observed with Nα-(O-phenyl)-phenethylphosphono]-l -alanyl-l -proline 2. Nα -(O-phenylphospho)-l -alanyl-l -proline, 3 Nα-(O, O′-diphenylphospho)-l -alanyl-l -proline 4, and Nα-2-(2-oxo-1, 3, 2-dioxaphosphiranyl)]-l -alanyl-l -proline 5 in deuterated dimethyl sulfoxide, deuterium oxide, and deuterochloroform. A ¹³C n.m.r. spectrum of 5 confirmed the presence of s-cis and s-trans resonances for the proline carbons in the same intensity ratio observed by ³¹P n.m.r.