泰利霉素和喹紅霉素工藝

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1、中文名稱泰利霉素別名紅霉酮(特利霉素)英文名稱?Telithromycin英文別名?KETEK;(1R,2R,4R,6S,7R,8R,10R,13R,14S)-7-[(2S,3R,4S,6R)-4-Dimethylamino-3-hydroxy-6-methyloxan-2-yl]oxy-13-ethyl-6-methoxy-2,4,6,8,10,14-hexamethyl-17-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-12,15-dioxa-17-azabicyclo[12.3.0]heptadecane-

2、3,9,11,16-tetroneCASNO.?191114-48-4EINECS?分子式C43H65N5O10分子結(jié)構(gòu)圖【藥物名稱】Telithromycin,RU-66647,HMR-3647,Levviax,Ketek化學(xué)結(jié)構(gòu)式(ChemicalStructure):參考文獻(xiàn)No.28301標(biāo)題:Novelerythromycinderivs.,methodfortheirpreparationandtheiruseasdrugs作者:Agouridas,C.;Chantot,J.-F.;Denis,A.;Gouind'Ambrieres,

3、S.;LeMartret,O.(AventisPharmaSA)來(lái)源:EP0680967;FR2719587;JP1996053489;JP1999152296;US5635485;WO9529929合成路線圖解說(shuō)明:Theselectivemesylationof2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycinA(I)withmethanesulfonicanhydridei

4、npyridinegivestheexpected11-O-methanesulfonylderivative(II),whichistreatedwith1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)inacetonetoyieldthe10,11-didehydroderivative(III).Theacylationof(III)withcarbonyldiimidazole(IV)bymeansofNaHinTHFaffordsthe12-O-acylderivative(V),whichisfinall

5、ycyclocondensedwith4-[4-(3-pyridyl)imidazol-1-yl]butylamine(VI)inhotacetonitrile.Theintermediatecompound4-[4-(3-pyridyl)imidazol-1-yl]butylamine(VI)isobtainedasfollows:ThecondensationofN-(4-bromobutyl)phthalimide(VII)with4-(3-pyridyl)imidazole(VIII)bymeansofNaHinDMFgivesN-[4-

6、[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide(IX),whichisthentreatedwithhydrazineinrefluxingethanol.參考文獻(xiàn)No.34565標(biāo)題:Novelerythromycinderivs.,theirprocessofpreparationandtheirapplicationasmedicines作者:Agouridas,C.;Chantot,J.F.;Denis,A.;Gouind'Ambrieres,S.;LeMartret,O.(AventisPha

7、rmaSA)來(lái)源:FR2732684合成路線圖解說(shuō)明:Theselectivemesylationof2'-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycinA(I)withmethanesulfonicanhydrideinpyridinegivestheexpected11-O-methanesulfonylderivative(II),whichistreatedwith1,8-

8、diazabicyclo[5.4.0]undec-7-ene(DBU)inacetonetoyieldthe10,11-didehydr