Chemoenzymatic Route to Poly(3-hydroxybutyrate) Stereoisomers

Racemic butyrolactone (BL) was selected to determine the feasibility of using enzyme catalysis in organic media for β-substituted β-propiolactone resolutions. Lipases from Candida cylindracia, Pseudomonas fluorescens (PS-30), and porcine pancreatic lipase Type II (PPL) were investigated. Based on reaction rate and the enantiomeric ratio E, PPL was found to be the most effective of these lipases. With respect to the organic media used, BL methanolysis occurred faster to slower as follows: n-hexane > diethyl ether > dioxane ≅ ethyl acetate > benzene. PPL-catalyzed BL methanolysis in n-hexane and diethyl ether reached ∼50% conversion in 22 h. Irrespective of the solvent used, the slower reacting enantiomer was (R)-BL. The E values for PPL-catalyzed BL resolutions carried out in diethyl ether, benzene, ethyl acetate, 1,4-dioxane, and hexane were 20.4 ± 2.4, 14.8 ± 2.3, 8.94 ± 1.28, 8.15 ± 1.04, and 5.56 ± 0.37, respectively. Thus, using PPL as the lipase in ether, 90%-(R)-BL was obtained in 35% yield. This monomer was polymerized using Zn(C2H5)2/H2O (1/0.6) as the catalyst to form predominantly (R)-poly(3-hydroxybutyrate) (P3HB) which had number-average molecular weight, melting point, and enthalpy of melting values of 41 300, 140 °C, and 64.6 J/g, respectively. Thus, a chemoenzymatic route to high molecular weight enantiomerically enriched P3HB was demonstrated.