Synthesis of alternating polydepsipeptides by ring-opening polymerization of morpholine-2,5-dione derivatives

Polydepsipeptides with alternating -hydroxy acid and -amino acid residues were synthesized by ring-opening polymerization of morpholine-2,5-dione derivatives. The polymerizations were performed in the melt using stannous octoate as an initiator. Molecular weights of the polydepsipeptides obtained ranged from 0,9 · 104 to 7,4 · 104. Morpholine-2,5-dione derivatives unsubstituted at the 6-position gave polymers with the highest molecular weights. Poly((S)-alanine-alt-glycolic acid) was semi-crystalline, whereas all other polydepsipeptides synthesized were amorphous. Morpholine-2,5-dione derivatives were synthesized by N-acylation of glycine, (S)-alanine or (S)-valine with chloroacetyl chloride or (R,S)-2-bromopropionyl bromide, followed by ring-closure of N-(2-halogenacyl)-amino acid sodium salts in the melt in 4 to 83% yield. Low yields in the cyclization reaction of N-(2-halogenacyl)-(S)-valine were accompanied by the formation of the corresponding polydepsipeptides in 13 to 46% yield, with molecular weights ranging from 3,3 · 104 to 4,9 · 104.