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

Abstract

Dedicated to Professor Herman F. Mark on the occasion of his 80th birthday ([>ate of receipt : Dcccm ber 17. 1974) SIJMMARY: Polydcpsipcptides with repeating units alanyl-lactyl and valyl-lactyl were synthesized by thcrmal polymeri7ation of the pcntachlorophenyl ester trifluoroacctatc salts of L-alanyl I -1actyl i.-alanyl 1.-lactic acid and i.-valyl ~.-lactyl ~.-valyl L-lactic acid.The depsidc linkages o f these monomers wcrc formed using N.N'-carbonyldiimidazolc and the pcptidc bond by coupling a A'-Boc-protected dcpside acid in thc presence of S.K'-dicycIohcxylcarbodiimide to a C-benzyl-protected dcpside amine. Alternativcly a K-Hoc-protected dcpsidc acid wascoupled by the mixed anhydridc method to the amino depside pentachlorophenyl ester. This was accomplishcd by taking advantage of thc different reaction rates of thc aminolysis of the mixed anhydridc and the pentachlorophcnyl ester. The thermal polymerization was carried out M ith the monomers dcpositcd o n a micron-sixd inorganic matrix, Kieselguhr. at temperatures between 100 and 1 2 0 T under high vacuum. Thc main fraction of polymer obtained had an average molecular weight (,D,<) of 20000-30OOO for poly(Ala-Lac) (10) and 80ooO--90000 for poly(Va1-Lac) (17). Typical yields for thcsc polymeri7ations wcrc 50 and 75"<,, respcctivcly. 7 he polLmers were found to bc frcc from racemimtion by two independent methods: total hydrolysis and hydrazinolysis

Degradable Poly(ester amide)s for Biomedical Applications

“…The third method based on an intramolecular amidation showed the lowest yields but some racemization at both C3 and C6 stereocenters. Polymerization of morpholine-2,5-diones were usually carried out in bulk using stannous octoate [Sn(Oct) 2 ] as a catalyst, at reaction temperatures close to the melting temperature of the monomer, and adding water or alcohol molecules as initiators [18]. It was postulated that the ring opening reaction was initiated by a tin (II) hydroxyl or alkoxide group.…”

Well‐Defined Poly(Ester Amide)‐Based Homo‐ and Block Copolymers by One‐Pot Organocatalytic Anionic Ring‐Opening Copolymerization of N‐Sulfonyl Aziridines and Cyclic Anhydrides

“…However, this yields by‐products and low molecular weight polymers with broad distributions. In contrast to polycondensation, ring‐opening polymerization (ROP) of morpholino‐2,5‐diones is more atom‐economical [2] . Furthermore, the ROP of morpholino‐2,5‐diones is generally catalyzed by metals or enzymes in bulk at high temperatures, resulting in uncontrolled products due to unavoidable side reactions; [3] a significant amount of organocatalysts is required to suppress side effects [4] .…”

“…In contrast to polycondensation, ring-opening polymerization (ROP) of morpholino-2,5-diones is more atom-economical. [2] Furthermore, the ROP of morpholino-2,5-diones is generally catalyzed by metals or enzymes in bulk at high temperatures, resulting in uncontrolled products due to unavoidable side reactions; [3] a significant amount of organocatalysts is required to suppress side effects. [4] The ring-opening copoly-merization of lactams and lactones can also produce copolymers with ester and amide linkages, although not alternating and contaminated by exchange transacylation reactions products.…”

Biodegradable Polydepsipeptides

“…Goodmann et al . reported that during cyclization the trifluoracetic salt of O -(α-aminoacyl)-1-methyl-2-oxo-2-(pentachlorophenoxy)ethyl ester is polycondensated to oligomers besides giving morpholine-2,5-diones as main products [ 39 ]. In’t Veld synthesized morpholine-2,5-diones in low yields (4%–10%) according to Method C [ 40 ].…”