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

Polydepsipeptides with alternating α‐hydroxy acid and α‐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.