摘要
β-脲基巴豆酸酯是合成6-甲基嘧啶二酮衍生物及3,4-二氢嘧啶二酮衍生物的重要中间体,在生物制药中有着广泛的应用.由于酶具有绿色、安全、高效的催化特性,采用α-糜蛋白酶为生物催化剂,以N,N-二甲基甲酰胺为反应介质,37℃条件下,通过1,3-二羰基化合物和脲的缩合反应,合成了一系列β-脲基巴豆酸酯类化合物.
β-Uramino crotonic esters are important intermediate for the synthesis of 6-methylpyrimidinedione derivatives and 3,4-dihydropyrimidinedione derivatives,and they have a wide range of applications in biopharmaceuticals. Enzymes have green,safe and highly efficient catalytic properties,so a series of β-uramino crotonic esters was synthesized via the α-chymotrypsin-catalyzed condensation reaction between 1,3-dicarbonyl compounds and ureas at37 ℃ and in DMF medium.
引文
[1]Gilberg E,Stumpfe D,Bajorath J.Towards a systematic assessment of assay interference:Identification of extensively tested compounds with high assay promiscuity[J].F1000research,2017,6:1505-1515.
[2]Mak J Y,Xu W,Reid R C,et al.Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells[J].Nat Commun,2017,8:14599-14612.
[3]Haline G O A,Tatiani B L,Aline L de O,et al.Facts,presumptions,and myths on the solvent-free and catalyst-free Biginelli reaction.What is catalysis for?[J].J Org Chem,2014,79(8):3383-3397.
[4]Nandi G C,Samai S,Singh M S.Biginelli and Hantzschtype reactions leading to highly functionalized dihydropyrimidinone,thiocoumarin,and pyridopyrimidinone frameworks via ring annulation withβ-oxodithioesters[J].J Org Chem,2010,75(22):7785-7795.
[5]Simón L,Goodman J M.A model for the enantioselectivity of imine reactions catalyzed by BINOL-phosphoric acid catalysts[J].J Org Chem,2011,76(6):1775-1788.
[6]Schneider P,Stutz K,Kasper L,et al.Target profile prediction and practical Evaluation of a biginelli-type dihydropyrimidine compound library[J].Pharm,2011,4(9):1236-1247.
[7]Majee A,Kundu S K,Santra S,et al.Chem Inform abstract:An improved procedure of miyashita protocol for the preparation of ureidomethylene derivatives of 1,3-dicarbonyl compounds[J].Cheminform,2014,45(20):124-126.
[8]Ehsan S,Khan B.Microwave synthesis ofβ-uramino crotonic ester and its derivatives[J].Asian J Chem,2011,23(7):3202-3204.
[9]a.Humble M S,Berglund P.Biocatalytic promiscuity[J].Eur J Org Chem,2011,2011(19):3391-3401.b.Lu Jia-wei(卢佳伟),Li You-ran(李由然),Shi Gui-yang(石贵阳).The modification of polyacrylonitrile hollow membrane by polyethyleneimine to immobilize lipase(聚乙烯亚胺改性聚丙烯腈中空膜固定脂肪酶)[J].J Mol Catal(China)(分子催化),2018,32(1):79-89.c.Lin Hui-ying(林惠颖),Xin Jia-ying(辛嘉英),Li Chun-yu(李春雨),et al.Progress on isolation and purification of particulate methane monooxygenase(颗粒性甲烷单加氧酶分离纯化方法的研究进展)[J].J Mol Catal(China)(分子催化),2018,32(1):90-98.d.Zheng Li-na(郑丽娜),Xin Jia-ying(辛嘉英),Wang Yan(王艳),et al.Research progress on the influence of microwave on enzyme-catalyzed reactions and the microwave effect(微波对酶催化反应的影响及其微波效应的研究进展)[J].J Mol Catal(China)(分子催化),2017,31(6):567-574.
[10]a.Busto E,Gotor-Fernandez V,Gotor V.Hydrolases:Catalytically promiscuous enzymes for non-conventional reactions in organic synthesis[J].Chem Soc Rev,2010,39:4504-4523.b.Li Chun-yu(李春雨),Xin Jia-ying(辛嘉英),Lin Hui-ying(林惠颖),et al.Study on functionalized gold nanoparticles of methanobactin by copper ion coordination uesd as simulated peroxidase(铜离子配位甲烷氧化菌素功能化纳米金模拟过氧化物酶的研究)[J].J Mol Catal(China)(分子催化),2017,31(5):480-485.
[11]Xin Jia-ying(辛嘉英).Lipase-catalyzed double kinetic resolution for the prepartion of high enantiopurity(S)-naproxen(脂肪酶催化二次动力学拆分制备高光学纯度(S)-萘普生)[J].J Mol Catal(China)(分子催化),2015,29(1):90-95.
[12]Wang Yan(王艳),Xin Jia-ying(辛嘉英),Yu Jia-qi(于佳琪).One step esterification synergy resolution synthesis(S)-naproxen starch ester by lipase in solvent system(脂肪酶催化一步酯化协同拆分合成S-萘普生淀粉酯)[J].J Mol Catal(China)(分子催化),2015,29(5):476-481.
[13]Hua X,Xing Y,Zhang X.Enhanced promiscuity of lipase-inorganic nanocrystal composites in the epoxidation of fatty acids in organic media[J].ACS Appl Materinter,2016,8(25):16257-16261.
[14]Lin B,Su H,Ma G,et al.Theoretical study of the hydrolysis mechanism of dihydrocoumarin catalyzed by serum paraoxonase 1(PON1):Different roles of Glu53and His115 for catalysis[J].Rsc Adv,2016,6(65):60376-60384.
[15]Wu W B,Xu J M,Wu Q.Promiscuous acylases-catalyzed markovnikov addition of n-heterocycles to vinyl esters in organic media[J].Adv Synth Catal,2006,348(4/5):487-492.
[16]Xie Z B,Wang N,Zhou L H,et al.Lipase-catalyzed stereoselective cross-aldol reaction promoted by water[J].Chem Cat Chem,2013,5(7):1935-1940.
[17]Lou F W,Liu B K,Wu Q.Candida antarctica lipase B(CAL-B)-catalyzed carbon-sulfur bond addition and controllable selectivity in organic media[J].Adv Synth Catal,2008,350(13):1959-1962.
[18]Guan Z,Fu J P,He Y H.Biocatalytic promiscuity:lipase-catalyzed asymmetric aldol reaction of heterocyclic ketones with aldehydes[J].Cheminform,2012,53(37):4959-4961.
[19]Zhang X D,Gao N,Guan Z,et al.Enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction for the synthesis of 1,2-dihydroquinolines using pepsin from porcine gastric mucosa[J].Chin Chem Lett,2016,27(6):964-968.
[20]Jiang,Ling,Hongwei.Enzymatic promiscuity:Escherichia coli bioh esterase-catalysed aldol reaction and knoevenagel reaction[J].Chem Res Chinese U,2014,30(2):289-292.
[21]Xu Jian-ming(许建明),Lin Xian-fu(林贤福).Catalytic promiscuity of enzyme and its new progress in organic synthesis(酶的催化多功能性及其在有机合成中的新进展)[J].Chin J Org Chem(有机化学),2007,27(12):1473-1478.
[22]Kumar A,Venkatesu P.Overview of the stability ofα-chymotrypsin in different solvent media[J].Chem Rev,2012,112(7):4283-4307.
[23]Liu Y,Liu R.The interaction ofα-chymotrypsin with one persistent organic pollutant(dicofol):Spectroscope and molecular modeling identification[J].Food Chem Toxicol,2012,50(9):3298-3305.
[24]Blow D M,Birktoft J J,Hartley B S.Role of a buried acid group in the mechanism of action of chymotrypsin[J].Nature,1969,221(5178):337-340.
[25]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.