Two-Step Enzymatic Synthesis of Biocompatible Polymers Made from Cholic Acid

Abstract

Polyesters are known biodegradable materials that are frequently used for biomedical applications that require biocompatibility. Their synthesis usually requires transition metal catalysts, which may become a source of contamination. In addition, using such compounds translates to extensive purification procedures, which do not agree with green chemistry principles. In addition to being renewable, enzymes such as lipases are milder for biological systems, and were studied for both ring-closure and ring-opening reactions. Here, Candida antarctica lipase B was used in ring-closure, reducing a two-step synthesis to a single step with 58% yield. The bile acid-containing macrocycles were subsequently polymerized with the same enzyme; relatively high molar masses (40 000 g/mol) were obtained. The conditions for the enzymatic ring-closure and ring-opening reactions were established through the reaction of thapsic acid with 1,10-decanediol. The di- and tetralactones afforded semicrystalline polymers with relatively high molar masses. Therefore, lipases were successfully used for both ring-closing reactions and ring-opening polymerizations of large rigid moieties as well as more flexible structures. The use of enzymes for the multistep syntheses shows their utility as a simple and green method for monomer and polymer synthesis with better biocompatibility and tunable properties.

Two-Way Reversible Shape Memory Polymers Made of Cross-Linked Cocrystallizable Random Copolymers with Tunable Actuation Temperatures

“…Only a few cocrystallizing polymer systems have been reported during past several decades. − In most cases, their synthesis is not easy and the T m difference is quite small. Gross’ group reported the copolymerization of ω-pentadecalactone (PDL) and ε-caprolactone (CL) catalyzed by Candida antartica lipase B (CALB), an enzyme with high efficiency for ring-opening polymerizations. − P­(CL- co -PDL) random copolymers undergo isomorphous substitution and can cocrystallize over the entire composition range. , The possibility of cocrystallization provides an ideal situation for the design of 2W-SMPs. To the best of our knowledge, the strategy of using cocrystallizable monomers has not yet been used in the preparation of 2W-SMPs.…”

Recent Progress in Macromolecular Design and Synthesis of Bile Acid‐Based Polymeric Architectures

“…Zhu and co-workers have synthesized CA-based cyclic polymers (Figure 4; P-6) using dilute Candida antarctica lipase B (CALB) enzyme solution via ring closing process. [62] They followed it with ring opening of the cyclic polymer using concentrated CALB which explores a nice prospect of enzyme assisted BAP design and synthesis. In addition, the same group worked on BA derived core confined polymer preparation to fabricate starlike supramolecular superstructures as reported by Myllymäki et al (Figure 4; P-7) [63] and Bertula et al [64] Recently, Cunningham et al have also designed CA cored PEG grafted star-shaped multi armed polymer [48] (Figure 5B) and folic acid (FA)-PEG armed CA-cored macromolecule for gene therapy applications.…”

Biotic and Abiotic Synthesis of Renewable Aliphatic Polyesters from Short Building Blocks Obtained from Biotechnology

“…The substrate concentration in as olvent is an important parameter for an enzymatic process because al ow substrate content may lead to the cyclization of oligomers to form macrocycles, [244,245] Reviews et al [249] determined that 350 wt %o fd iphenyl ether (vs. total mass of monomers) was optimal for the transesterification of bis(2,2,2-triflurorethyl) sebacate with 1,4-BDOa t3 7 8Cb yt he crude R. miehei lipase. Jiang et al showed that 150 wt %o fd iphenyle ther was the optimal solventa mount for the N435catalyzed transesterification reactiono fd iethyl succinate, dimethyl itaconate, and 1,4-BDO in diphenyl ether at 80 8C.…”

“…The substrate concentration in as olvent is an important parameter for an enzymatic process because al ow substrate content may lead to the cyclization of oligomers to form macrocycles, [244,245] and the final molar mass can be decreased if the optimal conditions are not applied. As some examples,L inko ChemSusChem 2018, 11,3836 -3870 www.chemsuschem.org et al [249] determined that 350 wt %o fd iphenyl ether (vs. total mass of monomers) was optimal for the transesterification of bis(2,2,2-triflurorethyl) sebacate with 1,4-BDOa t3 7 8Cb yt he crude R. miehei lipase.…”