Morpholine dione cyclic

Scheme 9.2 Synthetic route of morpholine-2,5-dione cyclic monomer.

Initially PDPs were synthesized by stepwise polycondensation of linear activated depsipeptide [93]. In 1985, Helder, Feijen and coworkers reported the synthesis of PDPs by ROP of a morpholine-2,5-dione derivative (cyclic dimer of ot-hydroxy- and a-amino acid cyclodepsipeptide, cDP) [94, 95]. The ROP method gives an alternative type of PDP by homopolymerization and also allows the copolymerization with other monomers (lactones and cyclic diesters) including LA, GA, and CL to give a wide variety of functional biodegradable materials. The synthesis of PDPs as functional biomaterials has been recently reviewed [17]. 

The enzymatic ROP of six-membered cyclic depsipeptides 3(S)-isopropyl-morpholine-2,5-dione, 3(R)-isopropyl-morpholine-2,5-dione, 3(R,S)-isopropyl-morpholine-2,5-dione, (3S, 6R, S)-3-isopropyl-morpholine-2,5-dione, 3(S)-isobutyl-morpholine-2,5-dione, 3(S)-sec-butyl-morpholine-2,5-dione, 6(S)-methyl-morpholine-2,5-dione and 6(R,S)-methyl-morpholine-2,5-dione has been reported [60]. 

Over the past few decades, many functionalized monomers for chemical modification of PLA were designed and synthesized, including (1) morpholine-2,5-dione derivatives, (2) a-amino acid A-carboxyanhydrides (NCA), (3) cyclic carbonates, and (4) lactones. The monomer units are introduced into the PLA backbones via ROP with lactide and the obtained copolymers are usually random copolymers, block copolymers or block copolymers with a third hydrophilic block - poly(ethylene glycol) (PEG). 

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