Polydepsipeptides with alternatiii .a-hydroxy acid and a-amino acid residues were synthesized by ring-opening polymerization 3 I 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 . lo4 to 1,4 * lo4. Morpholine-2,5-dione derivatives unsubstituted at the &position gave polymers with the highest molecular weights. Poly((S)-alaninealt-glycolic acid) was semi-crystalline,. whereas all other polydepsipeptides synthesized were amorphous. Morphoiine-2,5-dione derivatives were synthesized by N-acylation of glycine, (S)alanine or (5')-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 -lo4. 0 1990, HUthig & Wepf Verlag, Base1CCC 0025-1 16X/90/$03.00