One Pot Synthesis Of Multi Chiral Components And Chiral Polyesters Via Enzymatic Method

Enzyme plays more and more important role in asymmetric synthesis as the development of today’s chemical society. The traditional enzyme-catalyzed kinetic resolution (KR) and dynamic kinetic resoltution (DKR) have become less efficient due to its excessive amount of acyl donor. This thesis is aimed to develop a more efficient and atom economical emzyme-catalyzed multicomponent resolution strategy. Some new synthesis strategy of chiral polyesters have also been investigated.A novel dynamic double kinetic resolution (DDKR) strategy under the co-catalysis of Raney Nickel/Lipase B from Candida antarctica (CAL-B) for simultaneous resolution of primary amines and secondary alcohols (or esters) in one-pot has been established. Through this method most of the ee values of obtained chiral products can reach to90%, and most of the conversion of esters were above40%. Most of the yields of alcohols and amides can also be above40%and93%respectively. Successful application of DDKR into the resolution of a series of racemic amines and secondary alcohols (or esters), even an important anti-arrhythmic agent (Mexiletine) were achieved.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.A new strategy for the synthesis of Poly (R-3-hydroxyl) butyrate (Poly (R-HB)) has been investigated. In this stratety hing molecular weight chiral polyester was obtained through polymerization of rac-ethyl-3-hydroxybutyrate and the molecular weight can reach to2.0×103Da. The successful combination of enzyme-catalyzed dynamic kinetic resolution and enzyme-catalyzed polymerization made this strategy more efficient.An efficient strategy for synthesis of chiral aliphatic polyesters with pendant functional groups via lipase-catalysed copolymerization of amino acid and diol has been developed. The N-functionalization D/L aspartic acid and glutamic acid were copolymerized with4-,6-,8-,12-membered diol. Nine polyesters with aromatic, aliphatic, heterocyclic and amidic pendant functional groups had been prepared. The highest molecular weight can reach to19.3×x103Da. The investigation of copolymerization of N-amide-L-Asp diesters and diol also gave a strong proof of mechanism of lipase-catalyzed copolymerization. This strategy has significant potential value in preparing biodegrade materials of tissue engineering and drug delivery.