Yakai Feng

Lipase‐catalyzed ring‐opening polymerization of morpholine‐2,5‐dione derivatives: A novel route to the synthesis of poly(ester amide)s

The enzymatic ring-opening polymerization of 6-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-6-methyl-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 in the bulk, was investigated by using the lipase PPL as a catalyst. In the absence of the enzyme, the monomers were recovered, indicating that the present polymerization proceeds through enzymatic catalysis. During the polymerization of morpholine-2,5-diones racemization of both the amino acid and the S-lactic acid moiety takes place. Enzymatic polymerization produces polydepsipeptides with a carboxylic acid group at one end and a hydroxyl group at the other one.

Lipase-Catalyzed Ring-Opening Polymerization of 3(S)-sec-Butylmorpholine-2,5-dione

Lipase-catalyzed ring-opening bulk polymerizations of 3(S)-sec-butylmorpholine-2,5-dione (BMD) were investigated, Selected commercial lipases were screened as catalysts for BMD polymerization at 110°C. Polymerizations catalyzed with 10 wt.-% of lipase PPL and PC result in BMD conversions of about 70% and in molecular weights of the products ranging from 5 500 to 10700. Lipases MJ, CR and ES showed lower catalytic activities for the polymerization of BMD. Poly(3-secbutylmorpholine-2,5-dione) has a carboxylic acid group at one end and a hydroxy group at the other end. During the polymerization racemization of the isoleucine residue takes place. Lipase PPL was selected for a more detailed study. The apparent rate of polymerization increases with increasing PPL concentration when the polymerization temperature is 110°C. When the PPL concentration is 5 and 10 wt-% with respect to the monomer, a conversion of about 70% is reached after 5 d and 3 d, respectively. while for a PPL concentration of 1 wt.-% the conversion is less than 7% even after 6 d. High concentrations of PPL (10 wt.-%) result in high M n values (<4 d). The high est molecular weight poly(BMD), M n = 19 900, resulted from a polymerization conducted at 120 °C with 5 wt.-% PPL for 6 d. The general trend observed by varying the polymerization temperature is as follows: (i) monomer conversion and M n increase with increasing reaction tem perature from 110 to 125°C, (ii) monomer conversion and perature from 110 to 125°C, (ii) monomer conversion and M n decrease with an increase in reaction temperature from 125 to 130°C, Water content was found to be an important factor that controls both the conversion and the molecular weight. With increasing water content, enhanced polymer ization rates are achieved while the molecular weight of poly(BMD) decreases.

Synthesis of Poly[(lactic acid)‐alt‐ or co‐((S)‐aspartic acid)] from (3S,6R,S)‐3‐[(Benzyloxycarbonyl)methyl]‐6‐methylmorpholine‐2,5‐dione

Poly[(lactic acid)-alt-((S)-β-benzyl aspartate)] was synthesized via ring-opening polymerization of (3S,6R,S)-3-[(benzyloxycarbonyl)methyl]-6-methylmorpholine-2,5-dione (Cyclo[lac-Asp(OBzl)] in the presence of Sn(oct) 2 as a catalyst at 140°C. Poly[(lactic acid)-co-((S)-β-benzyl aspartate)] was obtained via copolymerization of Cyclo[Lac-Asp(OBzl)] with D,L-lactide under the same conditions. The protective benzyl groups of these copolymers ware completely removed by catalytic hydrogenation to give biodegradable poly[lactide-alt- or co-((S)-aspartic acid)]. Poly[lactide-alt- and co-((S)-aspartic acid)] are amorphous polymers. The glass-transition temperature of the copolymers after deprotection is higher than that of copolymers before deprotection.

Synthesis and characterization of new ABA triblock copolymers with poly[3(S)‐isobutylmorpholine‐2,5‐dione] and poly(ethylene oxide) blocks

ABA type block copolymers with poly[3(S)-isobutylmorpholine-2,5-dione] (PIBMD, A) and poly(ethylene oxide) (M n = 6000, PEO, B) blocks, PIBMD-b-PEO-b-PIBMD, were synthesized via ring-opening polymerization of 3(S)-isobutylmorpholine-2,5-dione in the presence of hydroxytelechelic poly(ethylene oxide) with stannous octoate as a catalyst. M n of the resulting copolymers increases with increasing 3(S)-isobutylmorpholine-2,5-dione content in the feed at constant mole ratio of monomer (M) to catalyst (C) (M/C = 125). No racemization of the leucine residue takes place during both homopolymerization of IBMD and polymerization of IBMD in the presence of PEO and Sn(Oct) 2 . The melting temperature of the PIBMD segments in the block copolymers depends on the length of the PIBMD blocks. The melting temperature of the PEO blocks is lower than that of the homopolymer, and the crystallinity of the PEO block decreases with increasing length of the PIBMD blocks. The PIBMD block crystallizes first upon cooling from the melt. This leads to only imperfect crystallization or no crystallization of the PEO blocks.

Synthesis and Characterization of New Block Copolymers with Poly(ethylene oxide) and Poly[3(S)-sec-butylmorpholine-2,5-dione] Sequences

Full Paper: Four different types of polydepsipeptide-polyether block copolymers were synthesized via ring-opening polymerization of 3(S)-sec-butylmorpholine-2,5-dione (BMD) in the presence of hydroxytelechelic poly-(ethylene oxide) (PEO) with stannous octoate as a catalyst. The polymers were an AB block copolymer, an ABA block copolymer, an (A) 2 B star shaped copolymer and an (A) 2 B(A) 2 copolymer, where A is a poly[3(S)-sec-butyl-morpholine-2,5-dione] (PBMD) and B a poly(ethylene oxide) block. The molar ratio of BMD to PEO was varied to obtain copolymers with different weight fractions of PBMD blocks ranging from 59.8 to 96.7 wt.-%, The crystallinity of the PEO phase in the copolymers decreases in the following order: AB > (A) 2 B > ABA > (A) 2 B(A) 2 . The static contact angle θ decreases with increasing PEO content in the block copolymers.

New biomaterial: triblock copolymers of poly [3(S)-isobutyl-morpholine-2,5-dione]-poly(ethylene oxide)

ABA-type block copolymers with poly[3(S)-isobutyl-morpholine-2,5-dione}(PIBMD, A) and poly(ethylene oxide) (M n = 6000, PEO, B) blocks, PIBMD-b-PEO-b-PIBMD, were synthesised via ring-opening polymerization of 3(S)-isobutyl-morpholine-2,5-dione in the presence of hydroxytelechelic poly(ethylene oxide) with stannous octoate as a catalyst. These block copolymers may find applications in cell encapsulation and in drug delivery. M n of the resulting copolymers increases with increasing 3(S)-isobutyl-morpholine-2,5-dione content in the feed at constant molar ratio of monomer (M) to catalyst (C) (M/C = 125). No racemization of the leucine residue takes place during both homopolymerization of IBMD and polymerization of IBMD in the presence of PEO and Sn(Oct) 2 . The melting temperature of the PIBMD segments in the block copolymers depends on the length of the PIBMD blocks. The melting temperature of the PEO blocks is lower than that of the homopolymer, and the crystallinity of the PEO block decreases with increasing length of the PIBMD blocks. The PIBMD block crystallizes first upon cooling from the melt. This leads to only imperfect crystallization or no crystallization of the PEO blocks.

Biodegradable copolymers based on poly(ethylene oxide), polylactide and polydepsipeptide sequences with functional groups

Abstract For the purpose of increasing the hydrophilicity of polylactide, new block copolymers with protected functional groups, poly(lactide-co-(S)-b-benzyl aspartate)-poly(ethylene oxide)-poly(lactide-co-(S)- b-benzyl aspartate), were synthesized via ring-opening polymerization of D,L-lactide and (3S, 6R,S)-3- [(benzyloxycarbonyl)methyl]-6-methylmorpholine-2,5-dione in the presence of hydroxyltelechelic poly(ethylene oxide) (PEO) as an initiator at 140 °C for 24 h. The benzyl protective groups of the block copolymers were completely removed to give poly(lactide-co-(S)-aspartic acid)-PEO-poly(lactide-co-(S)-aspartic acid), (poly(DLLA-co-Asp)-b-PEO-b-poly(DLLA-co-Asp)). This shows lower crystallization and melting temperature compared with the polymers before deprotection. Poly(DLLA-co-Asp)-b-PEO-b-poly(DLLA-co-Asp) with 55.6 wt.-% of PEO is more hydrophilic, shows higher water absorption and is degraded faster than with 39.5 wt.-% of PEO.