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Enzyme-catalyzed Bis-Michael Reaction And Catalyst-free Synthetic Spiro Epoxidized Indole Compound In Water

Posted on:2018-06-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2321330536973132Subject:Organic Chemistry
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Green chemistry is also known as environmentally friendly chemistry,clean chemistry,harmless chemistry.Green chemistry aims to reduce or eliminate environmental pollution by chemical means.So green chemistry is a complete strategy for pollution control,has always been one of the hot research area of chemistry.Enzymes are highly effective and green catalysts in the organism.Since enzymes were discovered to maintain their activities in organic solvents by Klibanov,they have gained increasing attention in the field of organic synthesis.Generally,the enzymes used for organic synthesis are commercially available.On the one hand,in order to maintain the stability and activities of the enzymes,various salts and additives are added during their factory production.On the other hand,these additives could greatly complicate the inquiry of mechanism.Therefore,in the second chapter of this paper,we tried to recombine and express porcine pepsin.We carried out tentative recombination and purification of porcine pepsin in pET28 a.The pure porcine pepsinogen was obtained after various trials.The test found that the resulting porcine pepsin was almost inactive and further methodological improvements were still in progress.The ability of an enzyme to catalyze the reaction of its non-natural substrate is called the enzyme catalytic promiscuity.The enzymes not only catalyze the organic reactions,but also exhibit excellent properties such as high stereoselectivity,wide substrate adaptability,mild reaction conditions in organic solvents.Nowadays,more and more studies have shown that the enzyme catalytic promiscuity is a ubiquitous nature.By far,Enzymes were found to be able to catalyze various kinds of reactions such as aldol reaction,Michael reaction,Mannich reaction,Henry reaction,Biginelli reaction and other reactions.Compounds containing quaternary carbon centers have been a hot topic because of their special stereochemistry and biological activity.Although many methods have been developed for the synthesis of quaternary carbon centers,Enzyme-catalyzed synthesis of these compounds is rare.It is still necessary to explore a safe and environmentally friendly protocol.In the third chapter of this paper,we studiedthe reaction of Bis-Michael catalyzed by amyloglucosidase to form quaternary carbon compounds.The influence of several factors,including solvent,water content,amount of substrate,time,solvent volume,enzyme loading,and temperature was investigated.Under the optimal reaction conditions,we obtained 12 examples,the desired products were obtained in excellent yields and diastereoselectivities(up to 92% yield and 99:1dr).at the same time,with the control test we give a proposed mechanism.The catalyst-free reaction in aqueous media has always been a concern for chemists because water is a cheap,easily available,green and sustainable solvent.In the fourth chapter of this paper,we studied the spontaneous Knoevenagel/cyclization reaction in the micelles formed by SDS and water to synthesize the spiro oxidized indole compounds.The influence of several factors,including solvent,time,SDS loading,and temperature was investigated.Under the optimal reaction conditions,we obtained 13 examples,the desired products were obtained in excellent yields(up to 94%yield).at the same time,with the control test we give a proposed mechanism.Compared with other catalysts,proline and its derivatives,as natural organic small molecule catalysts,have their own unique advantages: non-toxic harmless,non-metal ions,no harm to the environment,low prices,easy availability and good stability.In the last chapter,we investigated the asymmetric Mannich reaction of N-phenylpyrrolidine and acetone under the action of proline and hemin.The influence of several factors,including solvent,amount of substrate,time,solvent volume,enzyme loading,and temperature was investigated,at the same time,with the control test we give a proposed mechanism for the asymmetric Minnich reaction.
Keywords/Search Tags:Enzyme-catalyzed, recombination and purification, enzyme promiscuity, Bis-Michael reaction, Knoevenagel/cyclization reaction
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