7-二乙氨基香豆素-3-烯丙端基化合物的合成及其荧光性质研究
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摘要
以4-二乙氨基水杨醛、丙二酸环亚异丙酯为原料,经Knoevenagel反应生成7-二乙氨基香豆素-3-羧酸,与氨基酸发生缩合反应后与3-溴丙烯反应,设计合成了3个目标化合物。结构经~1HNMR、~(13)CNMR、ESI-MS等加以表征,并对其荧光性质进行测定。结果表明,3种烯丙端基化合物收率均超过70%,荧光发射峰波长分别为489、498、508 nm,其中7-二乙氨基香豆素-3-酰胺-N-丁酸烯丙酯具有相对较大的Stokes位移,对A549细胞进行染色,绿光激发时,细胞呈现出强烈的绿色荧光,成功实现细胞内荧光成像,具有良好的生物应用前景。
7-Diethylamino-coumarin 3-carboxylic acid was synthesized from 4-diethylamino-salicylaldehyde and cycloisopropyl malonate via Knoevenagel reaction.Three 7-diethylamine coumarin-3-allyl terminal compounds were designed and synthesized by 7-diethylamino-coumarin 3-carboxylic acid reacting with amino acid first and then with 3-bromopropene.The structures were confirmed by ~1HNMR,~(13)CNMR and ESI-MS,and their fluorescence properties were measured.The results showed that the yields of all three allyl end compounds were over 70%,and the fluorescence emission peaks were 489,498 and 508 nm,respectively.A549 cells stained by 7-diethylamine coumarin-3-carboxamido-N-allyl butyrate with a relatively large Stokes shift showed strong green fluorescence when stimulated by green light.Therefore,it has been successfully realized the fluorescence imaging in cells,which has a good prospect of the biological application.
7-Diethylamino-coumarin 3-carboxylic acid was synthesized from 4-diethylamino-salicylaldehyde and cycloisopropyl malonate via Knoevenagel reaction.Three 7-diethylamine coumarin-3-allyl terminal compounds were designed and synthesized by 7-diethylamino-coumarin 3-carboxylic acid reacting with amino acid first and then with 3-bromopropene.The structures were confirmed by ~1HNMR,~(13)CNMR and ESI-MS,and their fluorescence properties were measured.The results showed that the yields of all three allyl end compounds were over 70%,and the fluorescence emission peaks were 489,498 and 508 nm,respectively.A549 cells stained by 7-diethylamine coumarin-3-carboxamido-N-allyl butyrate with a relatively large Stokes shift showed strong green fluorescence when stimulated by green light.Therefore,it has been successfully realized the fluorescence imaging in cells,which has a good prospect of the biological application.
引文
[1]KEMPEN I,PAPAPOSTOLOU D,THIERRY N,et al.3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumor growth in vivo[J].Br.J.Cancer,2003,88(7):1 111-1 118.
[2]FYLAKTAKIDOU K C,LITINAS K E,NICOLAIDES D N,et al.Natural and synthetic coumarin derivatives with antiinflammatory/antioxidant activities[J].Curr.Pharm.Des.,2004,10(30):3 813-3 833.
[3]NASR T,BONDOCK S,YOUNS M.Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives[J].Eur.J.Med.Chem.,2014,76(7):539-548.
[4]GOMEZ-OUTES A,SUAREZGEA M L,CALOV-ROJAS G,et al.Discovery of anticoagulant drugs:a historical perspective[J].Curr.Drug Discov.Technol.,2012,9(2):83-104.
[5]HELA L A,RASHID M H O,CHOI C,et al.Chromogenic and fluorogenic sensing of Cu2+ based on coumarin[J].Tetrahedron,2011,67(15):2 794-2 802.
[6]CHEN J,LI S,ZHANG L,et al.Light-harvesting and photoisomerization in benzophenone and norbornadiene-labeled poly (aryl ether) dendrimers via intramolecular triplet energy transfer[J].J.Am.Chem.Soc.,2005,127(7):2 165-2 171.
[7]DANKO M,SZABO E,HRDLOVIC P.Synthesis and spectral characteristics of fluorescent dyes based on coumarin fluorophore and hindered amine stabilizer in solution and polymer matrices[J].Dyes Pigments,2011,90(2):129-138.
[8]YANAGI T,OTSUKA S,KASUGA Y,et al.Metal-free approach to biaryls from phenols and aryl sulfoxides by temporarily sulfur-tethered regioselective C—H/C—H coupling[J].J.Am.Chem.Soc.,2016,138(44):14 582-14 585.
[9]雷英杰,吴新世,张国春.4-香豆素基-2-芳基氨基噻唑的超声辅助合成及抗菌活性研究[J].化学试剂,2018,40(6):518-522.
[10]雷震霖,侯文成,骆焱平.7-醚基香豆素衍生物的合成及抑菌活性研究[J].化学试剂,2016,38(2):157-162.
[11]MANGASULI S N,HOSAMANI K M,DEVARAJEGOWDA H C,et al.Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents[J].Eur.J.Med.Chem.,2018,146(2):747-756.
[12]罗先金,宋健,程侣柏,等.新型香豆素荧光染料的合成及应用[J].中国科学(B辑),2001,31(6):542-547.
[13]SONG A,WANG X,LAM K S.A convenient synthesis of coumarin-3-carboxylic acids via Knoevenagel condensation of Meldrum′s acid with ortho-hydroxyaryl aldehydes or ketones[J].Tetrahedron Lett.,2003,44(9):1 755-1 758.
[2]FYLAKTAKIDOU K C,LITINAS K E,NICOLAIDES D N,et al.Natural and synthetic coumarin derivatives with antiinflammatory/antioxidant activities[J].Curr.Pharm.Des.,2004,10(30):3 813-3 833.
[3]NASR T,BONDOCK S,YOUNS M.Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives[J].Eur.J.Med.Chem.,2014,76(7):539-548.
[4]GOMEZ-OUTES A,SUAREZGEA M L,CALOV-ROJAS G,et al.Discovery of anticoagulant drugs:a historical perspective[J].Curr.Drug Discov.Technol.,2012,9(2):83-104.
[5]HELA L A,RASHID M H O,CHOI C,et al.Chromogenic and fluorogenic sensing of Cu2+ based on coumarin[J].Tetrahedron,2011,67(15):2 794-2 802.
[6]CHEN J,LI S,ZHANG L,et al.Light-harvesting and photoisomerization in benzophenone and norbornadiene-labeled poly (aryl ether) dendrimers via intramolecular triplet energy transfer[J].J.Am.Chem.Soc.,2005,127(7):2 165-2 171.
[7]DANKO M,SZABO E,HRDLOVIC P.Synthesis and spectral characteristics of fluorescent dyes based on coumarin fluorophore and hindered amine stabilizer in solution and polymer matrices[J].Dyes Pigments,2011,90(2):129-138.
[8]YANAGI T,OTSUKA S,KASUGA Y,et al.Metal-free approach to biaryls from phenols and aryl sulfoxides by temporarily sulfur-tethered regioselective C—H/C—H coupling[J].J.Am.Chem.Soc.,2016,138(44):14 582-14 585.
[9]雷英杰,吴新世,张国春.4-香豆素基-2-芳基氨基噻唑的超声辅助合成及抗菌活性研究[J].化学试剂,2018,40(6):518-522.
[10]雷震霖,侯文成,骆焱平.7-醚基香豆素衍生物的合成及抑菌活性研究[J].化学试剂,2016,38(2):157-162.
[11]MANGASULI S N,HOSAMANI K M,DEVARAJEGOWDA H C,et al.Synthesis of coumarin-theophylline hybrids as a new class of anti-tubercular and anti-microbial agents[J].Eur.J.Med.Chem.,2018,146(2):747-756.
[12]罗先金,宋健,程侣柏,等.新型香豆素荧光染料的合成及应用[J].中国科学(B辑),2001,31(6):542-547.
[13]SONG A,WANG X,LAM K S.A convenient synthesis of coumarin-3-carboxylic acids via Knoevenagel condensation of Meldrum′s acid with ortho-hydroxyaryl aldehydes or ketones[J].Tetrahedron Lett.,2003,44(9):1 755-1 758.