Lipase Catalyzed Knoevenagel Condensation And Its Application In Multi-component Tandem Reaction

The catalytic promiscuity of numerous enzymes have been reported recentlywith the development of enzymology. It refers to the ability of an enzyme ofcatalyzing completely different types of reactions relative to the natural reaction.Enzyme promiscuity has attracted a growing interest for chemists, because enzymepossesses the intrinsic advantages such as high catalytic efficiency, mild reactionconditions, non-toxic, etc.. In this paper, we would research an environment-friendlyand economically feasible way for organic synthesis through exploring lipasepromiscuity.Knoevenagel condensation is a useful and widely C-C bond formation reactionemployed in producing β-enones/enoesters in organic synthesis. Lipase from porcinepancreas (PPL) was firstly used to catalyze Knoevenagel condensation betweenα,β-unsaturated aldehydes and active methylene compounds. The effect of reactionconditions including enzyme sources, solvents, water content, enzyme loading, etc.,was systematically tested. And we found that PPL exhibited Z/E selectivity accordingto the structure geometry and the reactivity of substrate. We proved that lipase wasresponsible for this reaction through the blank test and completely denatured enzymetest. The proposed mechanism of the lipase-catalyzed Knoevenagel condensationbetween α,β-unsaturated aldehydes was presented.Lipase from porcine pancreas (PPL) was firstly reported to catalyzed synthesisof substituted2H-chromenes by a three component reaction. It was essential toexplore it owing to their pharmacological activities. The effect of reaction conditionsincluding enzyme sources, solvents, water content, reaction tempreture and structureof substrates, was systematically tested. We proved that the spatial structure of theenzyme was responsible for this reaction through a series of reaction including blanktest, completely denatured enzyme and BSA test. The proposed mechanism of thelipase-catalyzed synthesis of substituted2H-chromenes by a three component reactionwas presented.The synthesis of benzo[g]chromene derivatives through a multicomponent reaction catalyzed by Candida sp. lipase (CSL) was reported for the first time.Benzo[g]chromene derivatives have been reported to be the very important precursors.The key point was that using a single lipase catalyzed a multicomponent reaction toobtain relatively complex structures. The effect of reaction conditions includingenzyme sources, solvents, water content, reaction tempreture and enzyme loading,was systematically tested. And we deliberated on effect of structure of substrates onthe synthesis of benzo[g]chromene derivatives. We proved that spatial structure of theenzyme was responsible for this reaction through a series of reaction including blanktest, completely denatured enzyme and BSA test. The proposed mechanism of thelipase-catalyzed synthesis of benzo[g]chromene derivatives through amulticomponent reaction was presented.