氟喹酮的合成

华西药学杂志2006 21(2):160~ 162W CJ.PS24.9 25.1 30.0 29.2 29.3 29.4 ,29.4 29.4 31.7，进一步将6的端羟基氧化成羧基经反复摸索,确定34.4 42.7 ,74.5 ,171.1 179.9。以较温和的Jone's试剂作为氧化剂不仅收率较高,1.2.5 外消旋药喇叭酸甲酯(8)的合成 将430 mg且后处理简便)。最终,我们通过7步反应以总收71.37mmol)溶于2ml乙醚和2ml甲醇混合液的率7.2%合成了外消旋药喇叭酸甲酯8。此方法的冰水浴中。滴加由1.03 g亚硝基甲基脲在10 ml乙成本低廉,反应条件较温和,适于大量合成,为进-醚中新制备的重氮甲烷/乙醚溶液在冰水浴中振摇步合成树脂糖苷创造了条件。至黄色不再褪去。减压浓缩残留物经硅胶柱层析纯化(环己烷-丙酮=25:1)，得200 mg白色固体8 ,参考文献:收率51.2%。mp 30°。'HNMR( 400 MHz ,CDCl3 )8 :[1] Pereda - Miranda R ,Mata R ,Anaya AL ,e al. Tricolorin A ,major0.81( 3H ,t = 6.8 Hz),1.20 ~1.34( 22H ,m ),phytogrowth inhibitor from ipomoea ticolori[J].J Nat Prod ,1993 56(4)S71 - 582.1.53~ 1.55(2H ,m),1.96( 1H ,s),2.21( 2H ,t ,J =[2 ]Noda N ,Tsuji K ,Miyahara K ,et al . Resin glycosides XXI ,tugua-7.6 Hz)3.46~3.49( 1H m)3.58( 3H s )。 ICNMRjalapins I - X ,the resin glycosides having long - chain fatty aeid( 100 MHz ,CDCl3 )δ :13.7 ,22.3 ,24.6 ,25. 1 ,25.4 ,groups from the root of merremia hungaiensic[ J ]. Chem Pharm Bull ,28.8 28.9 29.1 29.3 ,29.4 31.7 ,33.7 ,37.2 ,37.2 ,1994 A2 10) 2011 - 2016.51.0 71.3 ,173.9。 EI- MS m/z 269( M+ - OH )215[3]Enriquez RC ,Leon I ,Peuez F vet al. Characterization ,by lwo - di-mensional NMR spectroscopy of a complex tetrasaccharide glycoside(M+-CsHu)isolated from ipomoea stans[°J] Can J Chem ,1992 ,70( 3 ):1000 -2讨论1008.[4]Furukawa J ,Sakairi N. Synthetic studies on resin glycosides[ J ]合成化合物4时,我们考察了温度对反应的影Trends in Glycosci Glycotech 2001 ,13(69):1- 10.响发现-78C时将正己醛的THF溶液( 1.4 mot[5]Brito - Arias M ,Pereda - Miranda R ,Heatheock CH. Synthesis of tri-colorin H J].J Org Chem 2004 69( 14 ) :4567 - 4570. .L-1)缓慢滴入格氏试剂中,能以较满意的收率.[6] Shioiri T ,Terao Y ,Irako N ,et al . Synthesis of topostins B567 and(74.5% )制得4而在室温下滴加则得不到4。合成D654( WB - 3559D ,lavoipin ) ,DNA topoisonerase 1 inhibitors of6时,发现室温无氢化反应温度过高则使产物复bacterial origi[ J ]. Tetrahedron ,1998 54 ( 51 ):15701 - 15710.杂最后确定在60C氢解制得6(收率80.0%)。为收稿日期2005-09.氟喹酮的合成肖瑞琪张国尧吴勇(四川大学华西药学院四川成都610041 )摘要:目的合成氟喹酮并改进工艺。 方法以2-氨基-5- 硝基苯甲酸为起始原料经缩合、还原、上保护基、环合、卤素交换、脱保护基共七步反应制得氟喹酮。结果和结论改 进后的方法避免了有毒有机溶剂的使用,在进行卤素交换反应时,用聚乙二醇作催化剂、无水二甲基甲酰胺代替乙二醇可以减少副产物收率也有所提高。产物经'HNMR ,IR ,MS 确证了结构。关键词:氟喹酮;肌松药合成中图分类号:R914.5文献标识码:A文章编号: 1006- 0103( 2006 )02 - 0160-03The synthesis of afloquanoneXIAO Rui-qi ZHANG Guo- yao ,WU Yong*( West China School of Pharmacy ,Sichuan Unirersity ,Chengdu 610041 ,China )Abstract : OBJECTIVE To synthesize aloquanone and inmprove the process.中国煤化工prepared daking 2 - aminio-5 - nitrobenzoic acid as initial malerial followed by condensation ,reduction pCN MH Ginge and dpolecion lollin 7 steps . RESULTS and CONCLUSION The method improved could avoid-neusage orsome poisonous soivent . The yield was increasedwith taking PEG as catalyst and anhydrous DMF as solvent instead of ethylene glycol . Chemical structure of product was identified by 'HNMR ,IR and MS.作者简介:肖瑞琪,女,正攻读药物化学专业的硕士学位。*通讯作者( Correspondent author)第2期肖瑞琪等。氟喹酮的合成161Key words : Afloquanone ;Muscle relaxant SyrthesisCLC number :R914.5Document code :AArticle ID :1006 - 0103( 2006 )02 - 0160 - 03氟喹酮( afloquanone的化学名称为6-氨基-2-经过二十多年的临床应用,证明是-个对面、颈部肌氟甲基-3-(2-甲苯基)-4-(3H)-喹唑啉酮，肉痉挛有良好疗效的松弛剂。是从上世纪70年代安眠酮(methaqualone)的结构修文献3]合成氟喹酮使用了剧毒的氟乙酸导致饰中所得,是对中枢神经起效的肌肉松弛药12。其难以工业化。为此我们选择了图1的合成路线。NH2C0OH1. soCl2/Toluene_ O2N、CONH1. H/Pd- c AcHN、CONH