药化合成整理共31页

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CHCH2CH3CH3CHCOOHCH3CH3CH2CHCH3Na－CCH2CHCH3CH3CH3COClAlCl3CHCH2CH3CH3CCH3OClCH2COOC2H5C2H5ONaCHCH2CH3CH3CCHCOOC2H5OCH3NaOHHClCHCH2CH3CH3CHCHOCH3CHCH2CH3CH3CHCOONaCH3Ag2O-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NSOOONaClCH2COOC2H5DMFNSOOCH2COOC2H5OC2H5ONaNHSOOHOOOMe2SO4NaOHNSOOHOOOCH3NNH2NSNOHOOOCH3H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，这是一个水解生成二甲胺与醛基反应，Et是乙基的缩写。ClNCHCH2CH2NCH3CH3CHCOOHCHCOOHNCH3Cl2NCH2ClNH2HClNCH2NH21NaNO2HCl2Cu2Cl2NCH2ClBrCH2CH（OEt）2NaNH2ClNCHCH2CH（OEt）2HCOOHDMFClNCHCH2CH2NCH3CH3CHCOOHCHCOOH雷尼替丁的合成ONCH2SNHCH3NHCH3CHNO2CH3OCHOOCH2OH（CH3）2NH，HCHOOCH2OH（CH3）2NCH2HSCH2CH2NH2OCH2SCH2CH2NH2（CH3）2NCH2CH3SC=CHNO2NHCH3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-2-硝基乙烯基）甲基硫醚12法莫替丁的合成NSCNHH2NHNSNH2NSO2NH2H2NCNHCNH2NHSCO(CH2Cl)2NSCH2Cl(H2N)2C=NH2NCNH2SNSCH2SCNH2(H2N)2C=NNHClCH2CH2CNNS(H2N)2C=NCH2SCNCH3OHNS(H2N)2C=NCH2SNHOCH3H2NSO2NH2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ClCH3ONH2Ac2OCH3ONHAcHNO3OH-CH3ONH2NO2H2NiCH3ONH2NH21CS2KOH2H+NNSHCH3OH12345醋酸孕甾双烯醇酮醋酸去氢表雄酮的合成OOHOEFAc2OC5H5NHClOOAcCrO3HAcCOCH3OCOAcOHAcCOCH3CNOHCH3NH2OHHClNHCOCH3POCl3PyH+OAcOAcOAcOAcOAcOAcO200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/吡啶雄性激素的合成OAcOOOOOHOHHOMnO2KBH4OHHOCH3OHOCH3OCOC2H5O[(CH3)2CHO]3AlO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二醇炔雌醇OAcOHAcCa(ClO)2AcOOOHClHgO,I2ClOAcOOH2SO4,H2CrO4OOClOCH3COOKOOOZn,H+OOHOCH2ArthrobacterSimplexOHOKBH4,CH3OHHOOHHCCHKOHiBuOHOHCHOCHClOOKOH，EtOHHO醋酸去氢表雄酮第一步是加成，第二步中先碘进攻，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沃氏氧化梨头霉菌CCH3OAcOCCH3OCCH3OOHHOOHOH2O2,NaOH,CH3OH1HBr2RaneyNi/H2I2,CaoHOCCH2IOOHKOAc,DMFCOOHHOCH2OAcCH2OAcCOOHOOCOOHCH2OAcHOOH3COMg,THFCH2=CHClOHH3COOOH3COOOTsOHH3COOH2Pd/CaCO3H3COOKBH4H3COOHLi,NH3H3COOHH3COOCHCKH3COOHCCHHClOOHCCHCH3COCH3,[(CH3)2CHO]3Al炔诺孕酮合成Ts：对甲苯磺酸五、环丙沙星的合成FFClCH2COClAlCl3COCH2ClFFEt3NNNNCOCH2FFNNN(CH3)3SOI-FFNNNCH2CCH2ONNNNNNCH2COHFFCH2NNN氟康唑的合成Aciclovir（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NNNNOHH2NHHH2NNNNNOSi(CH3)3HONNNNH2NOOO水解HH2NONNNNCH2OCH2CH2OH(CH3)3SiClXCH2OCH2CH2OCOCH312C2H5OHZidovudine（齐多夫定）合成NNOOCH3HHNNOHCH3HO(CH3)3SiClNNCH3OSi(CH3)3(CH3)3SiOOOAcOAcOAcAcO12NH3HNNOOCH3OOHOHHOHOOHONNOOCH3HCH3CH2COBrBr[H]LiN3HOONNOOCH3HN3HOOHONNOOCH3HHFClCCF2N(C2H5)2HOONNOCH3O胸腺嘧啶第二步是硅醚化，第三步是缩合环磷酰胺的合成POCl3Py(ClCH2CH2)2NPClClOH2NCH2CH2CH2OHEt3NH2ONHHOCH2CH2HOCH2CH2NPONHO(ClCH2CH2)2NPONHO(ClCH2CH2)2H2ON经POCl3，一个Cl离去卡莫司汀的合成OHNH2+OH2NH2NDMFONHOH2NOHHONNOHHHOSOCl2ClNNClHHONaNO2HCOOHClNNClHONO氟尿嘧啶的合成ClCH2COOC2H5KFCH3CONH2FCH2COOC2H5HCOOC2H5CH3ONa[OHCCHFCOOC2H5]CH3ONaC=CCOOC2H5HNaOCH3OCNH2NHCH3OHNNFOHCH3OHClNNFOOHHF返回NSCH3CH3COOHONHO酰化酶NSH2NCH3CH3COOHO（6-APA）6-APA的来源氨苄西林的合成方法1酰氯法CHCOOHNH2SOCl2CHCOClNH2HCl6-APAEt3NNSCH3CH3COOHONHONH2乙酰化方法2酸酐法CHCOOHNH2NSCH3CH3COOHONHONH2CHCOONaNH3CCH2COOC2H5CH3COCH2COOEtCHCOONaNH3CCHCOC2H5OHClCOOEtCHCOOCOOEtNH3CCHCOC2H5OHAPANSCH3CH3COONaONHONHCCHCOOEtH3C6-CHCOOHNH2CHOCN-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NSCH3COOCH2CCl3O7-ADCA酯CHNHCOOCH2CCl3COClCHCONHNHOCl3CCH2OZnHCOOHNSCH3COOHOCHCONHNH2第一步酯键水解，随后再水解既得氯霉素的合成COCH3O2NBr2COCH2BrO2N（CH2）6N4Delepine反应COCH2BrO2N（CH2）6N4HClCOCH2NH2O2NHCl（CH3CO）2OCOCH2NHCOCH3O2NHCHO，C2H5OHTollens缩合CCHCH2OHO2NONHCOCH3Al（iOPr）3MeerweinPonndorf还原CCHCH2OHO2NNHCOCH3HOH1、HCl，H2O2、15%NaOHCCHCH2OHO2NNH2HOH拆分CCHCH2OHO2NNH2HOHD（-）Cl2CHCOOCH3CCHCH2OHO2NHOHNHCOCHCl2谢谢！