Enzymatic Promiscuity:Hydrolase-catalyzed Michael Reaction And Domino Reaction

Biocatalysis have their inherent advantages such as higher substrate selectivity, milder reaction conditions, lower energy requirements, fewer byproducts and less steps of synthetic reaction over chemocatalysis. Moreover, the enzyme can be completely degraded, environment-friendly, widespread presence within the living body, which makes it become the attractive biocatalyst in the current concept of green chemistry and sustainable development. Traditional theory holds that the enzyme can catalyze the natural substrate and show the efficiency and specificity characteristics. Until the early 1980 s, researchers found that enzyme not only could catalyze chemical conversion of natural substrates in natural aqueous environment, but also have the ability to catalyze other non-natural substrates, which characteristics is defined as enzymatic promiscuity. In recent years, researchers found that many kinds of enzymes are capable of catalyzing the formation of carbon-carbon bond and carbon-heteroatom bond, and the products were obtained with good yields and selectivities. But so far,there is not a general way to discover catalytically promiscuous of enzyme. Catalytically promiscuous reactions can be secondary activities hidden behind a native activity and it is difficult to be discovered. As the increasing demand for industrial biocatalysts, which promote to explore the untapped development of the catalytic potential of natural enzyme, and broaden the range of enzymatic conversion, and increase the synthesis efficiency. In this paper, Hydrolase-catalyzed Michael reaction and domino reaction were investigated.Cyclopropane ring is found in multifarious naturally-occurring compounds from plants and microorganisms, which can undergo chemical transformations to build a variety of bioactive intermediates for synthesizing other more complex substances. This paper reported an enantioselective one-pot synthesis of nitrocyclopropanes via Michael addition initiated ring-closure sequence reactions of bromonitroalkane to α,β-unsaturated enones. The effects of solvents, base type, water contents, molar ratio, and temperature were investigated. Under the optimized conditions, Moderate to favorable yields(up to 93%) and enantioselectivities(up to 22% ee) were obtained. This strategy provide a convenient and biocatalytic method for green organic synthesis. Meanwhile, it provided a sustainable synthetic route for the synthesis of nitrocyclopropanes.Dihydropyrans are an important heterocyclic structural motif widely occurring in numerous natural and synthetic products. Many of these compounds exhibit intriguing biological activities, such as cytotoxicity against some cancers, anti-HCV entry, and anti-infectivity activities, and are widely used in pharmaceuticals. Protease from Streptomyces griseus as a sustainable biocatalyst was successfully applied in the Michael addition and cyclization reaction between cyclic dimedone and α,β-unsaturated ketones. The effects of solvents, enzyme loading, water contents, and temperature on the yield and selectivity of the reaction were investigated. It was found that either α,β-unsaturated ketones substituted by aryl or alkyl can well react with dimedone to synthesize dihydropyran derivatives. And up to 95% yields and certain stereoselectivities were obtained.Michael addition is an addition reaction of a nucleophilic reagent to α,β-unsaturated carbonyl compounds, which is the main means to build a C-C bond or Chetero bond. In this paper protease from Streptomyces griseus catalyzed 1,3-dicarbonyl compounds and maleimide to achieve a carbon-carbon bond through Michael reaction, and the products having two consecutive chiral centers. The reaction expanded the application of enzymatic promiscuity, 25 compounds were synthesized, 18 of these compounds were new compounds, and the best yield was 91%.