α-Aminosulfonopeptides as possible functional analogs of penicillin; evidence for their extreme instability

Sulfonopeptide analogs of acyl-D-Ala-D-Ala bearing an α-aminosulfonic acid moiety in the penultimate position have been synthesized using a Curtius rearrangement step. The sulfonopeptides were prepared and examined in aprotic solvents, but they proved to be exceedingly labile in protic solvents; for example, α-acylaminosulfonodipeptide 31 proved to be too unstable to isolate in pure form and its methyl ester, 34, decomposed with a half-life of ca. 8 min in 50% methanol at pD=5 and at 25°C. A mechanistic study relating to the stability of the α-sulfonopeptides is delineated, including an analysis of the decomposition products in aqueous solution.