Lipase‐Catalyzed Doubly Enantioselective Ring‐Opening Resolution between Alcohols and Lactones: Synthesis of Chiral Hydroxyl Esters with Two Stereogenic Centers

Abstract

A novel lipase B from Candida antarctica‐catalyzed doubly enantioselective ring‐opening resolution between racemic alcohols and lactones was developed. By using this strategy, three optically pure compounds including hydroxyl esters with two stereogenic centers and recovered alcohols and lactones were obtained simultaneously in high yields and ee. This process was used for the resolution of various racemic alcohols with different substituent groups and lactones with different ring sizes (four‐ and seven‐ membered lactones). The scale‐up experiments were also successful. Moreover, molecular docking was performed to explain the molecular basis of this doubly enantioselective ring‐opening resolution. As an attractive and efficient strategy, lipase‐catalyzed doubly enantioselective ring‐opening resolution will be widely used in the synthesis of optically pure hydroxyl esters with two stereogenic centers.

Recent advances in the synthesis of biodegradable polyesters by sustainable polymerization: lipase-catalyzed polymerization

“…55 In the past few years, the construction of endfunctionalized polyesters through the use of initiators has sprung enzymatic polyester synthesis, examples include the use of the copolymer of poly(ethylene glycol) and d-decalactone to induce the copolymerization of u-pentadecalactone to prepare an amphiphilic block copolymer, 56 propargyl alcohol, 6mercapto-1-hexanol or 2-bromoisobutyrate to initiate the polymerization of 3-caprolactone, 57,59 OH-terminated macroinitiator folate-conjugated poly(ethylene glycol) or methoxy poly(ethylene glycol) (mPEG) to initiate the copolymerization of dimethyl trimethylene carbonate and 5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one, 60 OH-functional chain transfer agent dodecyl 4-(hydroxymethyl) benzyl carbonotrithioate to initiate the polymerization of u-pentadecalactone, and 1-phenylethanol to initiate the polymerization of 3-methyl propiolactone. 61 In the ring-opening polymerization of 3-methyl propiolactone with 1-phenylethanol as initiator, various catalytic systems have been compared and the in vitro enzyme catalysis approach showed the molar ratio of lactones to alcohols had the most signicant effect on the reaction results, considering the over-consumption of lactones by the undesired polymerization so the lactones were excess compared with alcohols. Notably, Fels et al rst proved that CALB was used for enzyme-catalyzed ring-opening polymerization of b-lactam to obtain unbranched poly(b-alanine) and nylon 3.…”

Enantio‐, Regio‐, and Chemoselective Lipase‐Catalyzed Polymer Synthesis

“…Thus, it will pave a way for enlarging the scope of enzymatic polymerization which will be beneficial for achieving the green polymerization route at an industrial scale. Xia et al successfully integrated enzymatic kinetic resolution of racemic alcohols and enantioselective ring opening of substituted lactones, which could be potential in the synthesis of optically pure hydroxyl esters with two stereogenic centers. However, owing to the utilization of small‐membered lactones, enzymatic polymerization could not be induced, and no chiral polymers were formed through this strategy.…”