Synthesis and Polymerization of N-Z-l-Serine-β-lactone and Serine Hydroxybenzotriazole Active Esters

The reaction of Z-L-serine la with 1-hydroxybenzotriazole (HOBt) in the presence of N,N′-dicyclohexylcarbodiimide (DCC) yielded oligomeric poly(N-Z-serine ester) 4a and not Z-L-serine-β-lactone (2, R = Z), as described in a widely cited report by König and Geiger. After modifying the reaction conditions, the elusive HOBt active ester of Z-L-serine (3, R = Z) was obtained in 90% yield. Bulk polymerization of 3 gave poly(Z-L-serine ester) 4a with a weight average molecular weight (M_w) of about 22 000 da. Reaction of N-protected serine derivatives 1b-d with HOBt and DCC afforded poly (serine esters) 4b-d directly, typically with M_w in excess of 20000 da. In contrast, N-Z-threonine 5 failed to yield poly(N-Z-threonine ester). The optical purity of L-serine was preserved during the synthesis of the HOBt active ester and the subsequent polymerization. The approach described here represents the first, convenient multigram synthesis of serine derived polyesters, new polymers with potential biomedical applications.