Enzyme Catalyzed Domino Reaction: Synthesis Of 2H-1-Benzopyran-2-one Derivatives

Enzymes have been widely used in modern organic synthesis due to their simple processing requirements, high selectivity, environmentally friendly fashion, and mild reaction conditions. The recent progress of catalytic promiscuity has greatly extended the application of enzyme catalysis. Some proteases and lipases were developed to catalyze Aldol and Mannich reactions. Thus exploration of new activities of enzymes becomes particularly fascinating and remains a great challenge.Domino reactions are sequential bond forming or breaking processes during which the subsequent transformations occur at the functionalities generated in the preceding step. The application of such cascade reactions has led to the development of a variety of elegant and effective synthetic methods. A multitude of single enzyme-catalyzed single-step transformations is known. However there are fewer examples which single enzyme catalyzes domino reactions, which means the single enzyme displayed a promiscuous activity to catalyze multistep conversions. Therefore, the development of new enzymatic catalysts by utilizing the biocatalytic promiscuity in domino reaction is still in great demand.2H-1-benzopyran-2-one and their derivatives have varied bioactivitives such as anti-inflammatory and analgesic activities, antimicrobial, anticancer, antioxidant activity, antiproliferative activity, and central nervous system modulating activities. Moreover, they are widely used as additives in food, perfumes, agrochemicals, cosmetics, pharmaceuticals. They also act as intermediates for the synthesis of chromenes, coumarones and 2-acylresorcinols. So the synthesis of 2H-1-benzopyran-2-one and their derivatives has engrossed substantial attention from organic and medicinal chemists for many years. However the conventional methods for 2H-1-benzopyran-2-one derivatives synthesis suffer from major drawbacks (drastic conditions, stoichiometric amounts of Lewis or mineral acids). In this thesis, an efficient approach to 2H-1-benzopyran-2-one and derivatives has been developed using Enzyme-catalyzed domino Knoevenagel/transesterification reaction in organic media.In chapter 2, an efficient approach to 2H-1-benzopyran-2-one and derivatives has been developed using a BLAP-catalyzed domino Knoevenagel/transesterification reaction in organic media. Furthermore, the control of enzymatic chemoselectivity could be realized by adjusting parameters including solvent, water content, temperature, effect of BLAP loading. Salicylaldehyde derivatives were successfully added to a series ofβ-keto ester in moderate to excellent yields to prepare 14 2H-1-benzopyran-2-one derivatives.In chapter 3, an efficient approach to 2H-1-benzopyran-2-one and derivatives has been developed enzyme E-catalyzed domino Knoevenagel/transesterification reaction in organic media, Furthermore, the control of enzymatic chemoselectivity could be realized by adjusting parameters including solvent, water content, temperature. Salicylaldehyde derivatives were successfully added to a series ofβ-keto ester in moderate to excellent yields to prepare 20 2H-1-benzopyran-2-one derivatives.