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1、布洛芬的合成第三步是亲核加成,氯进攻羰基C。第四步中右边的丙酸脱去后重排CHCH2CH3CH3CHCOOHCH3CH3CH2CHCH3NaCCH2CHCH3CH3CH3COClAlCl3CHCH2CH3CH3CCH3OClCH2COOC2H5C2H5ONaCHCH2CH3CH3CCHCOOC2H5OCH3NaOHHClCHCH2CH3CH3CHCHOCH3CHCH2CH3CH3CHCOONaCH3Ag2O-Cu2ONaOHH+吡罗昔康的合成第二步中在前一个化合物中N和羰基O中间的键断裂,原先直接与N连接的C和羰基C相连NSOOONaClCH2COOC2H5DMFNSOOCH2COOC2H5OC
2、2H5ONaNHSOOHOOOMe2SO4NaOHNSOOHOOOCH3NNH2NSNOHOOOCH3H塞来昔布的合成甲醇钠使羰基氧右边的那个C上的H变酸性,CF3CO2C2H5上的羰基C进攻与羰基连接的那个C,第二个化合物是酮式与烯醇式的互变异构,第一步反应连接后先酮式再转变为烯醇式。NNFFFSOH2NOCH3CH3CH3OCF3CO2C2H5CH3ONa/Et2OCH3OCF3OHNHNH2SH2NOOEtOH.HCl马来酸氯苯那敏的合成第三步NaNO2的目的是重氮化,红色的为关键中间体,NaNH2的目的是强碱提供H,HCOOH作为还原剂,DMF的意思是N,N-二甲基甲酰胺,这是一个水解
3、生成二甲胺与醛基反应,Et是乙基的缩写。ClNCHCH2CH2NCH3CH3CH COOHCH COOHNCH3Cl2NCH2ClNH2HClNCH2NH21 NaNO2 HCl2 Cu2Cl2NCH2ClBrCH2CH(OEt)2NaNH2ClNCHCH2CH(OEt)2HCOOHDMFClNCHCH2CH2NCH3CH3CHCOOHCHCOOH 雷尼替丁的合成雷尼替丁的合成ONCH2SNHCH3NHCH3CHNO2CH3OCHOOCH2OH(CH3)2NH,HCHOOCH2OH(CH3)2NCH2HSCH2CH2NH2OCH2SCH2CH2NH2(CH3)2NCH2CH3SC=CHNO2N
4、HCH3第二步是Mannich反应,第四步中的CH3-S极易离去。CH3NO2CS2KOHO2NCH=CSKSKCH3OHO2NCH=CSCH3SCH3CH3NH2O2NCH=CNHCH3SCH3(1-甲氨基甲氨基-2-硝基乙烯基)甲基硫醚硝基乙烯基)甲基硫醚12 法莫替丁的合成法莫替丁的合成NSCNHH2NHNSNH2NSO2NH2H2NCNHCNH2NH SCO(CH2Cl)2NSCH2Cl(H2N)2C=NH2NCNH2SNSCH2SCNH2(H2N)2C=NNHClCH2CH2CNNS(H2N)2C=NCH2SCNCH3OHNS(H2N)2C=NCH2SNHOCH3H2NSO2NH2奥
5、美拉唑的合成奥美拉唑的合成 NH3CCH3CH3LiTHFNH3CCH3CH3H2O2NH3CCH3CH3OHNO3H2SO4NH3CCH3CH3ONO2CH3ONaCH3OHNH3CCH3CH3OOCH3Ac2ONH3CCH3CH2OAcOCH3NaOHNH3CCH3CH2OHOCH3SOCl2NH3CCH3CH2ClOCH3NNHSOCH3HNH3CCH3CH2SOCH3NNOCH3HmCPBANCH2SOCH3OCH3H3CHNNOCH3第一步是亲核取代,第二步是氧化,后硝化,第四步的目的是引入甲氧基,Ac2O作为酸酐,后水解,再卤代,再SH-亲核取代ClCH3ONH2Ac2OCH3ON
6、HAcHNO3OH-CH3ONH2NO2H2NiCH3ONH2NH21 CS2KOH2 H+NNSHCH3OH12345醋酸孕甾双烯醇酮醋酸孕甾双烯醇酮醋酸去氢表雄酮的合成醋酸去氢表雄酮的合成O OO OH H O OE EF FA A c c2 2O OC C5 5H H5 5N N H H C C l lO OO OA A c cC C r rO O3 3H H A A c cC C O O C C H H3 3O OC CO OA A c cO OH H A A c cC C O O C C H H3 3C CN N O O H HC C H H3 3N N H H2 2O O H H
7、H H C C l lN N H H C C O O C C H H3 3P PO O C C l l3 3P Py yH H+O OA A c cO OA A c cO OA A c cO OA A c cO OA A c cO OA A c cO O200度或对甲苯磺酸1、水解2、沃氏氧化睾丸素甲基睾丸素丙酸睾丸素1、格氏反应2、水解沃氏氧化(少量)丙酸酐/吡啶雄性激素雄性激素的合成的合成O OA A c cO OO OO OO OO O H HO O H HH H O OM M n nO O2 2K K B B H H4 4O O H HHOC C H H3 3O O H HO OC C
8、 H H3 3O O C C O O C C2 2H H5 5O O(CH3)2CHO3AlO甲苯CH3MgBr,乙醚醋酸去氢表雄酮沃式氧化即AcO的水解,由于共轭更稳定,故双键也改变了位置,KBH4还原,随后成酯的目的是可以口服雌激素合成雌激素合成雌二醇雌二醇炔雌醇炔雌醇O OA A c cO OH H A A c cC C a a(C C l l O O)2 2A A c cO OO OO O H HC C l lH H g gO O,I I2 2C C l lO OA A c cO OO OH H2 2S SO O4 4,H H2 2C C r rO O4 4O OO OC C l lO
9、 OC C H H3 3C C O O O O K KO OO OO OZ Zn n,H H+O OO O H H O O C C H H2 2 A A r rt th hr ro ob ba ac ct te er r S Si i m m p pl l e ex xO OH H O OK K B B H H4 4,C C H H3 3O O H HH H O OO O H HH H C CC C H HK K O O H Hi i B B u uO O H HO O H HC CH H O OC C H HC C l lO OO OKOH,EtOHHO醋酸去氢表雄酮第一步是加成,第二步中先
10、碘进攻,再氧化汞进攻,第六步的反应是在酸性条件下开环炔诺酮的合成氢化可的松的合成氢化可的松的合成沃氏氧化梨头霉菌C CC C H H3 3O OA A c cO OC CC C H H3 3O OC CC C H H3 3O OO O H HH H O OO OH H O OH H2 2O O2 2,N N a aO O H H,C C H H3 3O O H H1 1 H H B B r r2 2R Ra an ne ey y N N i i/H H2 2I I2 2,C C a ao oH H O OC CC C H H2 2I IO OO O H HK K O O A A c c,D D
11、 M M F FC CO OO O H HH H O OC C H H2 2O O A A c cC C H H2 2O O A A c cC CO OO O H HO OO OC CO OO O H HC C H H2 2O O A A c cH H O OOH3COMg,THFCH2=CHClOHH3COOOH3COOOTsOHH3COOH2Pd/CaCO3H3COOKBH4H3COOHLi,NH3H3COOHH3COOCHCKH3COOHC CHHClOOHC CHCH3COCH3,(CH3)2CHO3Al炔诺孕酮合成炔诺孕酮合成Ts:对甲苯磺酸五、环丙沙星的合成五、环丙沙星的合成 FF
12、ClCH2COClAlCl3COCH2ClFFEt3NNNNCOCH2FFNNN(CH3)3SO I-FFNNNCH2CCH2ONNNNNNCH2COHFFCH2NNN氟康唑的合成氟康唑的合成Aciclovir(阿昔洛韦)合成(阿昔洛韦)合成法1NNNNOH2NHHAc2OHHONNNNAcHNAcOO对甲苯磺酸HONNNNAcHNCH2OCH2CH2OAc水解HH2NONNNNCH2OCH2CH2OH可以把氨基和羰基相连的部分看做是N=C-OH法 2返回返回NNNNOHH2NHHH2NNNNNOSi(CH3)3HONNNNH2NOOO水解HH2NONNNNCH2OCH2CH2OH(CH3)3
13、SiClXCH2OCH2CH2OCOCH312 C2H5OHZidovudine(齐多夫定)合成(齐多夫定)合成NNOOCH3HHNNOHCH3HO(CH3)3SiClNNCH3OSi(CH3)3(CH3)3SiOOOAcOAcOAcAcO12NH3HNNOOCH3OOHOHHOHOOHONNOOCH3HCH3CH2COBrBrHLiN3HOONNOOCH3HN3HOOHONNOOCH3HHFClC CF2N(C2H5)2HOONNOCH3O胸腺嘧啶胸腺嘧啶第二步是硅醚化,第三步是缩合环磷酰胺的合成环磷酰胺的合成POCl3Py(ClCH2CH2)2NPClClOH2NCH2CH2CH2OHEt
14、3NH2ONHHOCH2CH2HOCH2CH2NPONHO(ClCH2CH2)2NPONHO(ClCH2CH2)2H2ON经POCl3,一个Cl离去卡莫司汀的合成卡莫司汀的合成OHNH2+OH2NH2NDMFONHOH2NOHHONNOHHHOSOCl2ClNNClHHONaNO2HCOOHClNNClHONO氟尿嘧啶的合成氟尿嘧啶的合成ClCH2COOC2H5KFCH3CONH2FCH2COOC2H5HCOOC2H5CH3ONa OHCCHFCOOC2H5CH3ONaC=CCOOC2H5HNaOCH3OCNH2NHCH3OHNNFOHCH3OHClNNFOOHHF返回返回NSCH3CH3CO
15、OHONHO酰化酶NSH2NCH3CH3COOHO(6-APA)6-APA6-APA的来源的来源氨苄西林的合成氨苄西林的合成方法方法1 酰氯法酰氯法CHCOOHNH2SOCl2CHCOClNH2HCl6-APAEt3NNSCH3CH3COOHONHONH2乙酰化方法方法2 酸酐法酸酐法CHCOOHNH2NSCH3CH3COOHONHONH2CHCOONaNH3CCH2COOC2H5CH3COCH2COOEtCHCOONaNH3CCHCOC2H5OHClCOOEtCHCOOCOOEtNH3CCHCOC2H5OHAPANSCH3CH3COONaONHONHCCHCOOEtH3C6-CHCOOHNH
16、2CHOCN-CHCNOHNH3CHCNNH2CO2CHCONHHNCOOH-H+1、2、dl(-)酒石酸拆分CHCOOHNH2D(-)NSCH3CH3COOKONHOClCOOCH2CCl3PyNSCH3CH3COOCH2CCl3ONHOHCOOHH2O2NSCH3CH3COOCH2CCl3OONHOH3PO4NSCH3COOCH2CCl3OHCH2ONHONSCH3COOCH2CCl3ONHOPCl5NSCH3COOCH2CCl3OClNCH3OHNSCH3COOCH2CCl3OOCH3NH2ONSCH3COOCH2CCl3H2NO7-氨基去乙酰氧基头孢烷酸三氯乙酯 (7-ADCA酯)第一步Cl进攻K,第三步开环,后缩合,后Cl取代羰基O,由于共轭稳定故双键转移,后甲醇进攻Cl,最后水解头孢氨苄的合成头孢氨苄的合成NSCH3COOCH2CCl3O 7-ADCA酯CHNHCOOCH2CCl3COClCHCONHNHOCl3CCH2OZnHCOOHNSCH3COOHOCHCONHNH2第一步酯键水解,随后再水解既得氯霉素的合成氯霉素的合成COCH3O2NBr2COCH2BrO2N(CH