Polydepsipeptides, 4 Synthesis of the alternating Polydepsipeptides Poly(Ala-Lac) and Poly(Val-Lac)

Polydepsipeptides with repeating units alanyl-lactyl and valyl-lactyl were synthesized by thermal polymerization of the pentachlorophenyl ester trifluoroacetate salts of L-alanyl L-lactyl L-ananyl L-lactic acid and L-valyl L-lactyl L-valyl L-lactic acid. The depside linkages of these monomers were formed using N,N′-carbonyldiimidazole and the peptide bond by coupling a N-Boc-protected depside acid in the presence of N,N′-dicyclohexylcarbodiimide to a C-benzyl protected despide amine. Alternatively a N-Boc-protected depside acid was coupled by the mixed anhydride method to the amino depside pentachlorophenyl ester. This was accomplished by taking advantage of the different reaction rates of the aminolysis of the mixed anhydride and the pentachlorophenyl ester. The thermal polymerization was carried out with the monomers deposite on a micro-sized inorganic matrix, Kieselguhr, at temperatures between 100 and 120°C under high vacuum. The main fraction of polymer obtained had an average molecular weight (M̄w) of 20000–30000 for poly(Ala-Lac) (10) and 80000–90000 for poly(Val-Lac) (17). Typical yields for these polymerizations were 50 and 75%, respectively. The polymers were found to be free from racemization by two independent methods: total hydrolysis and hydrazinolysis of the alternating ester bonds. The degradation products were investigated for their optical purity by measurements of circular dichroism. optical rotation. and L-lactate dchydrogenase digestion.