Synthesis and enzymatic degradation of optically active depsipeptide copolymers

This paper describes the synthesis and biodegradation of copolymers of cycl ic depsipeptide with epsilon-caprolactone (CL) or lactide (LA), Optically a ctive cyclic depsipeptides, 3,6-dimethyl-2,5-morpholinediones (DMOs), were prepared by the reaction of an amino acid (D-, L-, or DL-alanine) with a hy droxy acid derivative (DL-2-bromopropionyl bromide). These isomers are abbr eviated as D-DMO, L-DMO and DL-DMO respectively, according to the names of alanine isomers. Then, we have prepared the copolymers of DMO isomers with CL using tin(II) octylate as a catalyst. The NMR spectra and thermal proper ties of DMO/CL copolymers revealed that these copolymers exist randomly. Th e enzymatic degradation of the copolymers has been examined using Rhizopus delemar lipase, cholesterol esterase (from Pseudomonas sp,), and Proteinase K (from Tritirachium album). Cholesterol esterase and Proteinase K show hi gh degradability, while the lipase shows little degradation. Among the enzy mes used, only Proteinase K could recognize the isomerism of DMO, resulting in the following order of degradability: copoly(L-DMO/CL) > copoly(DL-DMO/ CL) > copoly(D-DMO/CL), i.e. this enzyme ha!, the highest substrate specifi city for naturally occurring L-alanine. Further, we have prepared the rando m copolymers of L-DMO with lactide (L-LA or DL-LA), and evaluated the enzym atic degradation of the copolymers by Proteinase K. The introduction of a s mall amount (up to c. 10 mol%) of L-DMO unit into LA homopolymers brought a bout greater degradability compared with LA homopolymers. In particular, L- DMO/L-LA copolymers with high degradability have been obtained without sign ificant decrease in the mechanical and thermal properties of L-LA homopolym er.