氟喹酮的合成

華西藥學(xué)雜志2006 21(2):160~ 162W CJ.PS24.9 25.1 30.0 29.2 29.3 29.4 ,29.4 29.4 31.7，進(jìn)一步將6的端羥基氧化成羧基經(jīng)反復摸索,確定34.4 42.7 ,74.5 ,171.1 179.9。以較溫和的Jone's試劑作為氧化劑不僅收率較高,1.2.5 外消旋藥喇叭酸甲酯(8)的合成 將430 mg且后處理簡(jiǎn)便)。最終,我們通過(guò)7步反應以總收71.37mmol)溶于2ml乙醚和2ml甲醇混合液的率7.2%合成了外消旋藥喇叭酸甲酯8。此方法的冰水浴中。滴加由1.03 g亞硝基甲基脲在10 ml乙成本低廉,反應條件較溫和,適于大量合成,為進(jìn)-醚中新制備的重氮甲烷/乙醚溶液在冰水浴中振搖步合成樹(shù)脂糖苷創(chuàng )造了條件。至黃色不再褪去。減壓濃縮殘留物經(jīng)硅膠柱層析純化(環(huán)己烷-丙酮=25:1)，得200 mg白色固體8 ,參考文獻: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討論1008.[4]Furukawa J ,Sakairi N. Synthetic studies on resin glycosides[ J ]合成化合物4時(shí),我們考察了溫度對反應的影Trends in Glycosci Glycotech 2001 ,13(69):1- 10.響發(fā)現-78C時(shí)將正己醛的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)緩慢滴入格氏試劑中,能以較滿(mǎn)意的收率.[6] Shioiri T ,Terao Y ,Irako N ,et al . Synthesis of topostins B567 and(74.5% )制得4而在室溫下滴加則得不到4。合成D654( WB - 3559D ,lavoipin ) ,DNA topoisonerase 1 inhibitors of6時(shí),發(fā)現室溫無(wú)氫化反應溫度過(guò)高則使產(chǎn)物復bacterial origi[ J ]. Tetrahedron ,1998 54 ( 51 ):15701 - 15710.雜最后確定在60C氫解制得6(收率80.0%)。為收稿日期2005-09.氟喹酮的合成肖瑞琪張國堯吳勇(四川大學(xué)華西藥學(xué)院四川成都610041 )摘要:目的合成氟喹酮并改進(jìn)工藝。 方法以2-氨基-5- 硝基苯甲酸為起始原料經(jīng)縮合、還原、上保護基、環(huán)合、鹵素交換、脫保護基共七步反應制得氟喹酮。結果和結論改 進(jìn)后的方法避免了有毒有機溶劑的使用,在進(jìn)行鹵素交換反應時(shí),用聚乙二醇作催化劑、無(wú)水二甲基甲酰胺代替乙二醇可以減少副產(chǎn)物收率也有所提高。產(chǎn)物經(jīng)'HNMR ,IR ,MS 確證了結構。關(guān)鍵詞:氟喹酮;肌松藥合成中圖分類(lèi)號:R914.5文獻標識碼:A文章編號: 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.中國煤化工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.作者簡(jiǎn)介:肖瑞琪,女,正攻讀藥物化學(xué)專(zhuān)業(yè)的碩士學(xué)位。*通訊作者( 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的化學(xué)名稱(chēng)為6-氨基-2-經(jīng)過(guò)二十多年的臨床應用,證明是-個(gè)對面、頸部肌氟甲基-3-(2-甲苯基)-4-(3H)-喹唑啉酮，肉痙攣有良好療效的松弛劑。是從上世紀70年代安眠酮(methaqualone)的結構修文獻3]合成氟喹酮使用了劇毒的氟乙酸導致飾中所得,是對中樞神經(jīng)起效的肌肉松弛藥12。其難以工業(yè)化。為此我們選擇了圖1的合成路線(xiàn)。NH2C0OH1. soCl2/Toluene_ O2N、CONH1. H/Pd- c AcHN、CONH