α-糜蛋白酶催化合成3,4-二氢嘧啶-2(1H)-酮
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摘要
以α-糜蛋白酶为生物催化剂,通过芳香醛、尿素和乙酰乙酸乙酯之间的Biginelli反应合成3,4-二氢嘧啶-2(1H)-酮类化合物,并对反应条件进行了优化。得到的最佳反应条件为:反应介质为乙醇,芳香醛、乙酰乙酸乙酯和尿素的物质的量比为1.0∶1.5∶1.0,α-糜蛋白酶用量为33.3%(以尿素质量为基准,下同),反应温度为60℃,反应时间为96 h。在该条件下,合成3,4-二氢嘧啶-2(1H)-酮衍生物,产率为55%～63%。
3,4-Dihydropyrimidin-2(1H)-one derivatives were synthesized via α-chymotrypsin-catalyzed Biginelli reaction between aromatic aldehyde, urea and ethyl acetoacetate.The reaction conditions for the synthesis of model compound were optimized.The optimal reaction conditions were obtained as follows:the reaction medium was ethanol, the molar ratio of aromatic aldehydes to ethyl acetoacetate and urea was1.0∶1.5∶1.0, the amount of α-chymotrypsin was 33.3%(based on the mass of urea,the same below), the reaction temperature was 60 ℃, and the reaction time was 96 h. Under these optimum reaction conditions,a series of 3,4-dihydropyrimidin-2(1H)-one derivatives with yields ranging from 55% to 63% were obtained.
3,4-Dihydropyrimidin-2(1H)-one derivatives were synthesized via α-chymotrypsin-catalyzed Biginelli reaction between aromatic aldehyde, urea and ethyl acetoacetate.The reaction conditions for the synthesis of model compound were optimized.The optimal reaction conditions were obtained as follows:the reaction medium was ethanol, the molar ratio of aromatic aldehydes to ethyl acetoacetate and urea was1.0∶1.5∶1.0, the amount of α-chymotrypsin was 33.3%(based on the mass of urea,the same below), the reaction temperature was 60 ℃, and the reaction time was 96 h. Under these optimum reaction conditions,a series of 3,4-dihydropyrimidin-2(1H)-one derivatives with yields ranging from 55% to 63% were obtained.
引文
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[13]Zheng S,Jian Y,Xu S,et al.N-Donor ligand activation of titanocene for the Biginelli reaction via the imine mechanism[J].RSC Advances,2018,8(16):8657-8661.
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[19]Sun H H,Zhang H F,Ang E L,et al.Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates[J].Bioorganic&Medicinal Chemistry,2018,26(7):1275-1284.
[20]Xie Z B,Sun D Z,Jiang G F,et al.Facile synthesis of bis(indolyl)methanes catalyzed byα-chymotrypsin[J].Molecules,2014,19(12):19665-19677.
[21]Xie Zongbo(谢宗波),Zhang Shiguo(张士国),Jiang Guofang(姜国芳),et al.pepsin-catalyzed synthesis of 2,3-dihydroquinazolin-4(1H)-onederivatives[J].Chinese Journal of Organic Chemistry(有机化学),2017,37(2):514-519.
[22]Wu Q,Liu B K,Lin X F.Enzymatic promiscuity for organic synthesis and cascade process[J].Current Organic Chemistry,2010,14(17):1966-1988.
[23]Chen Y L,Li W,Liu Y,et al.Trypsin-catalyzed direct asymmetric aldol reaction[J].Journal of Molecular Catalysis B-Enzymatic,2013,87(3):83-87.
[24]Xie B H,Guan Z,He Y H.Promiscuous enzyme-catalyzed Michael addition:synthesis of warfarin and derivatives[J].Journal of Chemical Technology and Biotechnology,2012,87(12):1709-1714.
[25]Xue Y,Li L P,He Y H,et al.Protease-catalysed direct asymmetric Mannich reaction in organic solvent[J].Scientific Reports,2012,2(10):761.
[26]Jetti S R,Jain S,Bhatewara A,et al.Silica-bonded-propyl sulfamic acid as an efficient recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under heterogeneous conditions[J].Chinese Chemical Letters,2014,25(3):469-473.
[27]Elhamifar D,Elhamifar D,Shojaeipoor F.Synthesis,characterization and catalytic application of a novel polyethylene-supported Fe/ionic liquid complex[J].Journal of Molecular Catalysis A:Chemical,2017,426:198-204.
[28]Nazari S,Saadat S,Fard P K,et al.Imidazole functionalized magnetic Fe3O4 nanoparticles as a novel heterogeneous and efficient catalyst for synthesis of dihydropyrimidinones by Biginelli reaction[J].Monatshefte Fur Chemie,2013,144(12):1877-1882.
[29]Wang J H,Zhang E,Tang G M,et al.Novel bipyridinyl oxadiazole-based metal coordination complexes:high efficient and green synthesis of 3,4-dihydropyrimidin-2(1H)-ones through the Biginelli reactions[J].Journal of Solid State Chemistry,2016,261:86-98.
[30]Zare A,Nasouri Z.A green approach for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones(and-thiones)using N,N-diethylN-sulfoethanaminium hydrogen sulfate[J].Journal of Molecular Liquids,2016,216:364-369.
[31]Rashmi S V,Sandhya N C,Raghava B,et al.Trifluoroethanol as a metal-free,homogeneous,and recyclable medium for the efficient one-pot synthesis of dihydropyrimidones[J].Cheminform,2012,42(3):424-433.
[32]Maleki A,Paydar R.Bionanostructure-catalyzed one-pot threecomponent synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives under solvent-free conditions[J].Reactive and Functional Polymers,2016,109:120-124.
[33]Liu Z Q,Ma R,Cao D W.New efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by benzotriazolium-based ionic liquids under solvent-free conditions[J].Molecules,2016,21(4):462.
[34]Damgaard M,Al-Khawaja A,Nittegaard-Nielsen,et al.Monastrol,a3,4-dihydropyrimidin-2(1H)-thione,as structural scaffold for the development of modulators for GHB high-affinity binding sites andα1β2δGABAA receptors[J].European Journal of Medicinal Chemistry,2017,138:300-312.
[35]Liu Y,Liu R.The interaction ofα-chymotrypsin with one persistent organic pollutant(dicofol):Spectroscope and molecular modeling identification[J].Food&Chemical Toxicology,2012,50(9):3298-3305.
[36]Kumar A,Venkatesu P.Overview of the stability ofα-chymotrypsin in different solvent media[J].Chemical Reviews,2012,112(7):4283-4307.
[2]Simón L,Goodman J M.A model for the enantioselectivity of imine reactions catalyzed by BINOL-phosphoric acid catalysts[J].Journal of Organic Chemistry,2011,76(6):1775-1788.
[3]Maksim A Kolosov,Olesia G Kulyk,Muataz J K,et al.An effective Biginelli-type synthesis of 1-methoxy-3,4-dihydropyrimidin-2(1H)-ones[J].Cheminform,2015,46(45):4666-4669.
[4]Shamim Shahbaz,Khan Khalid Mohammed,Salar Uzma,et al.5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones:As potent urease inhibitors;synthesis,in vitro screening,and molecular modeling study[J].Bioorganic Chemistry,2018,76:37-52.
[5]Crespo A,El M A,Biagini P,et al.Discovery of 3,4-dihydropyrimidin-2(1H)-ones as a novel class of potent and selective A2B sdenosine receptor antagonists[J].ACS Medicinal Chemistry Letters,2013,4(11):1031-1036.
[6]Shen Z L,Xu X P,Ji S J.ChemInform Abstract:Broensted base catalyzed one-pot three-component Biginelli-type reaction:an efficient synthesis of 4,5,6-triaryl-3,4-dihydropyrimidin-2(1H)-one and mechanistic study[J].Cheminform,2010,41(24):1162-1167.
[7]Bose D S,Fatima L,Mereyala H B.Green chemistry approaches to the synthesis of 5-alkoxycarbonyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones by a three-component coupling of one-pot condensation reaction:comparison of ethanol,water,and solvent-free conditions[J].Journal of Organic Chemistry,2003,68(2):587-590.
[8]Slimi H,Moussaoui Y,Salem R B.Synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones via Biginelli reaction promoted by bismuth(Ⅲ)nitrate or PPh3 without solvent[J].Arabian Journal of Chemistry,2016,9:S510-S514.
[9]Lal J,Sharma M,Sahu P K,et al.Multi-component one-pot synthesis of 4-aryl substituted dihydropyrimidinones and mechanistic study under solvent-free conditions using NiO2 as heterogeneous recyclable green catalyst[J].Proceedings of the National Academy of Sciences India,2013,83(3):187-193.
[10]Karimi-Jaberi Z,Moaddeli M S.Synthesis of 3,4-dihydropyrimidin-2(1H)-ones and their corresponding 2(1H)thiones using trichloroacetic acid as a catalyst under solvent-free conditions[J].Isrn Organic Chemistry,2012,2012(1/2):1-4.
[11]Moussa S B,Lachheb J,Gruselle M,et al.Calcium,Barium and Strontium apatites:A new generation of catalysts in the Biginelli reaction[J].Tetrahedron,2017,73(46):6542-6547.
[12]Nagarajaiah H,Mukhopadhyay A,Moorthy J N.Biginelli reaction:An overview[J].Tetrahedron Letters,2016,57(47):5135-5149.
[13]Zheng S,Jian Y,Xu S,et al.N-Donor ligand activation of titanocene for the Biginelli reaction via the imine mechanism[J].RSC Advances,2018,8(16):8657-8661.
[14]Alvim H G O,Lima T B D,Oliveira H C B D,et al.Ionic liquid effect over the Biginelli reaction under homogeneous and heterogeneous catalysis[J].ACS Catalysis,2013,3(3):1420-1430.
[15]Lei M,Ma L,Hu L.An efficient and environmentally friendly procedure for synthesis of pyrimidinone derivatives by use of a Biginelli-type reaction[J].Monatshefte fur Chemie,2010,141(9):1005-1008.
[16]Borse B N,Borude V S,Shukla S R.Synthesis of novel dihydropyrimidin-2(1H)-ones derivatives using lipase and their antimicrobial activity[J].Current Chemistry Letters,2012,1:59-68.
[17]Sharma U K,Sharma N,Kumar R,et al.Biocatalysts for multicomponent Biginelli reaction:bovine serum albumin triggered waste-free synthesis of 3,4-dihydropyrimidin-2-(1H)-ones[J].Amino Acids,2013,44(3):1031-1037.
[18]Busto E,Gotor-Fernandez V,Gotor V.Hydrolases:Catalytically promiscuous enzymes for non-conventional reactions in organic synthesis[J].Chemical Society Reviews,2010,39:4504-4523.
[19]Sun H H,Zhang H F,Ang E L,et al.Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates[J].Bioorganic&Medicinal Chemistry,2018,26(7):1275-1284.
[20]Xie Z B,Sun D Z,Jiang G F,et al.Facile synthesis of bis(indolyl)methanes catalyzed byα-chymotrypsin[J].Molecules,2014,19(12):19665-19677.
[21]Xie Zongbo(谢宗波),Zhang Shiguo(张士国),Jiang Guofang(姜国芳),et al.pepsin-catalyzed synthesis of 2,3-dihydroquinazolin-4(1H)-onederivatives[J].Chinese Journal of Organic Chemistry(有机化学),2017,37(2):514-519.
[22]Wu Q,Liu B K,Lin X F.Enzymatic promiscuity for organic synthesis and cascade process[J].Current Organic Chemistry,2010,14(17):1966-1988.
[23]Chen Y L,Li W,Liu Y,et al.Trypsin-catalyzed direct asymmetric aldol reaction[J].Journal of Molecular Catalysis B-Enzymatic,2013,87(3):83-87.
[24]Xie B H,Guan Z,He Y H.Promiscuous enzyme-catalyzed Michael addition:synthesis of warfarin and derivatives[J].Journal of Chemical Technology and Biotechnology,2012,87(12):1709-1714.
[25]Xue Y,Li L P,He Y H,et al.Protease-catalysed direct asymmetric Mannich reaction in organic solvent[J].Scientific Reports,2012,2(10):761.
[26]Jetti S R,Jain S,Bhatewara A,et al.Silica-bonded-propyl sulfamic acid as an efficient recyclable catalyst for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones/thiones under heterogeneous conditions[J].Chinese Chemical Letters,2014,25(3):469-473.
[27]Elhamifar D,Elhamifar D,Shojaeipoor F.Synthesis,characterization and catalytic application of a novel polyethylene-supported Fe/ionic liquid complex[J].Journal of Molecular Catalysis A:Chemical,2017,426:198-204.
[28]Nazari S,Saadat S,Fard P K,et al.Imidazole functionalized magnetic Fe3O4 nanoparticles as a novel heterogeneous and efficient catalyst for synthesis of dihydropyrimidinones by Biginelli reaction[J].Monatshefte Fur Chemie,2013,144(12):1877-1882.
[29]Wang J H,Zhang E,Tang G M,et al.Novel bipyridinyl oxadiazole-based metal coordination complexes:high efficient and green synthesis of 3,4-dihydropyrimidin-2(1H)-ones through the Biginelli reactions[J].Journal of Solid State Chemistry,2016,261:86-98.
[30]Zare A,Nasouri Z.A green approach for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones(and-thiones)using N,N-diethylN-sulfoethanaminium hydrogen sulfate[J].Journal of Molecular Liquids,2016,216:364-369.
[31]Rashmi S V,Sandhya N C,Raghava B,et al.Trifluoroethanol as a metal-free,homogeneous,and recyclable medium for the efficient one-pot synthesis of dihydropyrimidones[J].Cheminform,2012,42(3):424-433.
[32]Maleki A,Paydar R.Bionanostructure-catalyzed one-pot threecomponent synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives under solvent-free conditions[J].Reactive and Functional Polymers,2016,109:120-124.
[33]Liu Z Q,Ma R,Cao D W.New efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by benzotriazolium-based ionic liquids under solvent-free conditions[J].Molecules,2016,21(4):462.
[34]Damgaard M,Al-Khawaja A,Nittegaard-Nielsen,et al.Monastrol,a3,4-dihydropyrimidin-2(1H)-thione,as structural scaffold for the development of modulators for GHB high-affinity binding sites andα1β2δGABAA receptors[J].European Journal of Medicinal Chemistry,2017,138:300-312.
[35]Liu Y,Liu R.The interaction ofα-chymotrypsin with one persistent organic pollutant(dicofol):Spectroscope and molecular modeling identification[J].Food&Chemical Toxicology,2012,50(9):3298-3305.
[36]Kumar A,Venkatesu P.Overview of the stability ofα-chymotrypsin in different solvent media[J].Chemical Reviews,2012,112(7):4283-4307.