藥化合成整理

1、布洛芬的合成第三步是親核加成，氯進攻羰基C。第四步中右邊的丙酸脫去后重排CHCH2CH3CH3CHCOOHCH3CH3CH2CHCH3NaCCH2CHCH3CH3CH3COClAlCl3CHCH2CH3CH3CCH3OClCH2COOC2H5C2H5ONaCHCH2CH3CH3CCHCOOC2H5OCH3NaOHHClCHCH2CH3CH3CHCHOCH3CHCH2CH3CH3CHCOONaCH3Ag2O-Cu2ONaOHH+吡羅昔康的合成第二步中在前一個化合物中N和羰基O中間的鍵斷裂，原先直接與N連接的C和羰基C相連NSOOONaClCH2COOC2H5DMFNSOOCH2COOC2H5OC

2、2H5ONaNHSOOHOOOMe2SO4NaOHNSOOHOOOCH3NNH2NSNOHOOOCH3H塞來昔布的合成甲醇鈉使羰基氧右邊的那個C上的H變酸性，CF3CO2C2H5上的羰基C進攻與羰基連接的那個C，第二個化合物是酮式與烯醇式的互變異構，第一步反應連接后先酮式再轉(zhuǎn)變?yōu)橄┐际?。NNFFFSOH2NOCH3CH3CH3OCF3CO2C2H5CH3ONa/Et2OCH3OCF3OHNHNH2SH2NOOEtOH.HCl馬來酸氯苯那敏的合成第三步NaNO2的目的是重氮化，紅色的為關鍵中間體，NaNH2的目的是強堿提供H，HCOOH作為還原劑，DMF的意思是N,N-二甲基甲酰胺，這是一個水解

3、生成二甲胺與醛基反應，Et是乙基的縮寫。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反應，第四步中的CH3-S極易離去。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奧

5、美拉唑的合成奧美拉唑的合成 NH3CCH3CH3LiTHFNH3CCH3CH3H2O2NH3CCH3CH3OHNO3H2SO4NH3CCH3CH3ONO2CH3ONaCH3OHNH3CCH3CH3OOCH3Ac2ONH3CCH3CH2OAcOCH3NaOHNH3CCH3CH2OHOCH3SOCl2NH3CCH3CH2ClOCH3NNHSOCH3HNH3CCH3CH2SOCH3NNOCH3HmCPBANCH2SOCH3OCH3H3CHNNOCH3第一步是親核取代，第二步是氧化，后硝化，第四步的目的是引入甲氧基，Ac2O作為酸酐，后水解，再鹵代，再SH-親核取代ClCH3ONH2Ac2OCH3ON

6、HAcHNO3OH-CH3ONH2NO2H2NiCH3ONH2NH21 CS2KOH2 H+NNSHCH3OH12345醋酸孕甾雙烯醇酮醋酸孕甾雙烯醇酮醋酸去氫表雄酮的合成醋酸去氫表雄酮的合成O OO OH HO OE EF FA Ac c2 2O OC C5 5H H5 5N N H HC Cl lO OO OA Ac cC Cr rO O3 3H HA Ac cC CO OC CH H3 3O OC CO OA Ac cO OH HA Ac cC CO OC CH H3 3C CN NO OH HC CH H3 3N NH H2 2O OH H H HC Cl lN NH HC CO OC

7、 CH H3 3P PO OC Cl l3 3P Py yH H+O OA Ac cO OA Ac cO OA Ac cO OA Ac cO OA Ac cO OA Ac cO O200度或?qū)妆交撬?、水解2、沃氏氧化睪丸素甲基睪丸素丙酸睪丸素1、格氏反應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 Ac cO OO OO OO OO OH HO OH HH HO OMMn nO O2 2K KB BH H4 4O OH HHOC CH H3 3O OH HO OC CH H3 3O OC CO OC C2 2H H5 5O O(CH3)2CHO3AlO甲苯CH3

8、MgBr，乙醚醋酸去氫表雄酮沃式氧化即AcO的水解，由于共軛更穩(wěn)定，故雙鍵也改變了位置，KBH4還原，隨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 Ac cO OH HA Ac cC Ca a( (C Cl lO O) )2 2A Ac cO OO OO OH HC Cl lH Hg gO O, ,I I2 2C Cl lO OA Ac cO OO OH H2 2S SO O4 4, ,H H2 2C Cr rO O4 4O OO OC Cl lO OC CH H3 3C CO OO OK KO OO OO OZ Zn n, ,H H+O OO O H HO O

9、C CH H2 2 A Ar rt th hr ro ob ba ac ct te er r S Si immp pl le ex xO OH HO OK KB BH H4 4, ,C CH H3 3O OH HH HO OO OH HH HC CC CH HK KO OH Hi i B Bu uO OH HO OH HC CH HO OC CH HC Cl lO OO OKOH，EtOHHO醋酸去氫表雄酮第一步是加成，第二步中先碘進攻，再氧化汞進攻，第六步的反應是在酸性條件下開環(huán)炔諾酮的合成氫化可的松的合成氫化可的松的合成沃氏氧化梨頭霉菌C CC CH H3 3O OA Ac cO OC C

10、C CH H3 3O OC CC CH H3 3O OO OH HH HO OO OH HO OH H2 2O O2 2, ,N Na aO OH H, ,C CH H3 3O OH H1 1 H HB Br r2 2R Ra an ne ey y N Ni i/ /H H2 2I I2 2, ,C Ca ao oH HO OC CC CH H2 2I IO OO OH HK KO OA Ac c, ,D DMMF FC CO OO OH HH HO OC CH H2 2O OA Ac cC CH H2 2O OA Ac cC CO OO OH HO OO OC CO OO OH HC CH

11、H2 2O OA Ac cH HO OOH3COMg, THFCH2=CHClOHH3COOOH3COOOTsOHH3COOH2Pd/CaCO3H3COOKBH4H3COOHLi, NH3H3COOHH3COOCHCKH3COOHC CHHClOOHC CHCH3COCH3,(CH3)2CHO3Al炔諾孕酮合成炔諾孕酮合成Ts：對甲苯磺酸五、環(huán)丙沙星的合成五、環(huán)丙沙星的合成 FFClCH2COClAlCl3COCH2ClFFEt3NNNNCOCH2FFNNN(CH3)3SO I-FFNNNCH2CCH2ONNNNNNCH2COHFFCH2NNN氟康唑的合成氟康唑的合成Aciclovir（阿昔洛

12、韋）合成（阿昔洛韋）合成法1NNNNOH2NHHAc2OHHONNNNAcHNAcOO對甲苯磺酸HONNNNAcHNCH2OCH2CH2OAc水解HH2NONNNNCH2OCH2CH2OH可以把氨基和羰基相連的部分看做是N=C-OH法 2返回返回NNNNOHH2NHHH2NNNNNOSi(CH3)3HONNNNH2NOOO水解HH2NONNNNCH2OCH2CH2OH(CH3)3SiClXCH2OCH2CH2OCOCH312 C2H5OHZidovudine（齊多夫定）合成（齊多夫定）合成NNOOCH3HHNNOHCH3HO(CH3)3SiClNNCH3OSi(CH3)3(CH3)3SiOOO

13、AcOAcOAcAcO12NH3HNNOOCH3OOHOHHOHOOHONNOOCH3HCH3CH2COBrBrHLiN3HOONNOOCH3HN3HOOHONNOOCH3HHFClC CF2N(C2H5)2HOONNOCH3O胸腺嘧啶胸腺嘧啶第二步是硅醚化，第三步是縮合環(huán)磷酰胺的合成環(huán)磷酰胺的合成POCl3Py(ClCH2CH2)2NPClClOH2NCH2CH2CH2OHEt3NH2ONHHOCH2CH2HOCH2CH2NPONHO(ClCH2CH2)2NPONHO(ClCH2CH2)2H2ON經(jīng)POCl3，一個Cl離去卡莫司汀的合成卡莫司汀的合成OHNH2+OH2NH2NDMFONHOH

14、2NOHHONNOHHHOSOCl2ClNNClHHONaNO2HCOOHClNNClHONO氟尿嘧啶的合成氟尿嘧啶的合成ClCH2COOC2H5KFCH3CONH2FCH2COOC2H5HCOOC2H5CH3ONa OHCCHFCOOC2H5CH3ONaC=CCOOC2H5HNaOCH3OCNH2NHCH3OHNNFOHCH3OHClNNFOOHHF返回返回NSCH3CH3COOHONHO?；窷SH2NCH3CH3COOHO（6-APA）6-APA6-APA的來源的來源氨芐西林的合成氨芐西林的合成方法方法1 酰氯法酰氯法CHCOOHNH2SOCl2CHCOClNH2HCl6-APAEt3N

15、NSCH3CH3COOHONHONH2乙?；椒ǚ椒? 酸酐法酸酐法CHCOOHNH2NSCH3CH3COOHONHONH2CHCOONaNH3CCH2COOC2H5CH3COCH2COOEtCHCOONaNH3CCHCOC2H5OHClCOOEtCHCOOCOOEtNH3CCHCOC2H5OHAPANSCH3CH3COONaONHONHCCHCOOEtH3C6-CHCOOHNH2CHOCN-CHCNOHNH3CHCNNH2CO2CHCONHHNCOOH-H+1、2、dl（-）酒石酸拆分CHCOOHNH2D（-）NSCH3CH3COOKONHOClCOOCH2CCl3PyNSCH3CH3COO

16、CH2CCl3ONHOHCOOHH2O2NSCH3CH3COOCH2CCl3OONHOH3PO4NSCH3COOCH2CCl3OHCH2ONHONSCH3COOCH2CCl3ONHOPCl5NSCH3COOCH2CCl3OClNCH3OHNSCH3COOCH2CCl3OOCH3NH2ONSCH3COOCH2CCl3H2NO7-氨基去乙酰氧基頭孢烷酸三氯乙酯 （7-ADCA酯）第一步Cl進攻K，第三步開環(huán)，后縮合，后Cl取代羰基O，由于共軛穩(wěn)定故雙鍵轉(zhuǎn)移，后甲醇進攻Cl，最后水解頭孢氨芐的合成頭孢氨芐的合成NSCH3COOCH2CCl3O 7-ADCA酯CHNHCOOCH2CCl3COClCHCONHNHOCl3CCH2OZnHCOOHNSCH3COOHOCHCONHNH2第一步酯鍵水解，隨后再水解既得氯霉素的合成氯霉素的合成COCH3O2NBr2COCH2BrO2N（C