Biocatalyst-catalyzed One Pot Multicomponent Reactions For The Synthesis Of Heterocyclic Compound

Multicomponent reactions(MCRs), an effective approach to construct the new complex diverse organic compound with high efficiency and low costing, have received the widespread attention over all the world. At present, the application of biological catalysts in MCRs, is attracting more and more attention in the field of chemistry. Due to its high efficiency, green and other characteristics, the biocatalyst has become a hot topic in green chemistry.Our group has been devoted to the study of the organic synthetic methodologies. To development of the green and efficient catalytic system and new synthetic methods is one of the focus in our research. Therefore, in this thesis we aim to screen some biocatalyst with high catalytic activity, and study the catalytic activities of MCRs under mild conditions. Through a series of multicomponent reaction, we obtain a variety of different heterocyclic compounds. The thesis mainly includes the following aspects:1. Porcine trypsin as an efficient catalyst in one pot three components reaction of2-bromo-1-phenylethan-1-one, amines and isothiocyanate phenyl ester for synehesis of thiazole-2-imine under mild reaction conditions. We have screened seven kinds of biocatalysts for this three components reaction. We found the porcine trypsin has good catalytic activity. So,we have synthesized a series of thiazole-2-imide derivatives under the optimized conditions, and10 products are new compounds.2. Bovine serum albumin(BSA), a ubiquitous and inexpensive, non-enzymatic transport protein, could serve as an efficient retrievable catalyst in one-pot four-component reaction of aryl aldehydes, malononitrile, hydrazine hydrate, and ethyl acetoacetate for the synthesis of pyrano[2,3-C]pyrazoles under mild reaction conditions. The BSA biocatalyst was found to work extremely well also for acyclic/cyclic ketones to give corresponding pyrano[2,3-C]pyrazoles or their spirocyclic variants. The BSA could be used for at least 5 cycles without significant loss of catalytic activity. This novel efficient protocol has the merits of high yield, simple operation,and environmental benign. Moreover, this method extends the promiscuity of BSA biocatalyst.3. Porcine trypsin as an efficient catalyst in one pot five components reaction of ethyl acetoacetate, hydrazine hydrate and aryl aldehydes for synehesis of4,4’-(arylmethylene)bis(1H-pyrazol-5-ol)s under mild reaction conditions has been described.Seven kinds of biocatalysts for this five components reaction have been screened. We found the porcine trypsin has good catalytic activity for this kind of transformation.