| Biocatalysis is the application of enzymes or organisms (cell, organelle, tissue, etc.) as a catalyst for chemical transformation of organic compounds. Enzymes which often exhibit excellent catalytic activity in chemical transformations are the most attractive biocatalysts. Enzyme catalytic promiscuity, in which the active site of an enzyme can catalyze more than one chemical transformation, has received widespread attention as more and more catalytic promiscuities of existing enzymes have been discovered. In this field, hydrolases have been mainly studied due to their commercial availability, high stability, broad substrate scope and high catalytic efficiency in medium containing organic solvents. To date, hydrolase catalysts in organic synthesis have been used widely. However uses for asymmetric carbon-carbon bond formation using the catalytic promiscuity of hydrolases are still scarce. Asymmetric carbon-carbon bond formation is an efficient and important approach for producing enantiopure or enantio-enriched compounds. Therefore, it is important to explore the application of the hydrolase enzyme’s catalytic promiscuity to discover alternate methods for asymmetric organic synthesis.Chiral 1,2-diols are very important building blocks often found in a vast array of natural and biologically active molecules. Using environmentally friendly, safe, and inexpensive enzyme biocatalysts, we successfully synthesized chiral 1,2-diols via an asymmetric aldol reaction of aromatic aldehyde with 1-hydroxypropan-2-one in acetonitrile without extra water which was catalyzed by pepsin from porcine gastric mucous. We explored the solvent effects, water content, the molar ratio of substrates, enzyme loading and temperature effects to optimize the reaction conditions. Under optimized conditions the pepsin-catalyzed aysmmeric aldol reaction has a wide scope of substrates that can tolerate aromatic aldehyde with acetones which were substituted by hydroxyl, dihydroxyl, methoxyland benzyloxy as substrates. This biocatalysis was also applicable to aldol reactions of cyclic and hetereocyclic ketones with aromatic aldehyde. After substrate expansion, yields of up to 87%, diastereoselectivities of up to> 99/1 dr and enantiose lectivities of up to 75% ee were achieved.Dihydropyrans are a class of very important compounds because the fragments of dihydropyran are vital building blocks of many natural products and bioactive molecules. Herein, a domino Michael addition/cyclization from 2-benzoyl-3-Arylacrylonitrile and cyclohexanone to synthesize substituted dihydropyran compounds catalyzed by protease from Streptomyces griseus under mild conditions without extra organic solvent was completed. After condition optimization and completing substrate expansion, we obtained some substituted dihydropyran compounds with moderate to high yields up to 91%, moderate diastereoselectives with dr up to 75/25, and moderate enatioselectivies with ee up to 25%. This method not only extended the application of protease from Streptomyces griseus in the field of biocatalysis, but also offered a valuable way for synthesizing dihydropyrans in organic synthesis.2-Amino-4H-chromenes and derivatives are classical examples of heterocyclic compounds. Numerous biologically active and natural products contain the important 2-amino-4H-chromene block. We developed a green one-pot domino reaction of Michael addition/cyclization, starting from readily available 2-hydroxychalcones with malononitrile, for the synthesis of 2-amino-4H-chromene derivatives catalyzed by BSA (bovine serum albumin) in ethanol. Under optimized conditions, we obtained products in yields of 26-96% through substrate expansion This biocatalytic method is suitable for the synthesis of chromene derivatives due to its high efficiency, environmentally friendliness and simplicity. |
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