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Vinflunine, L-0070, F-12158, Javlor

长春氟宁Chemical Name: 4(R)-Acetoxy-9-[4(R)-(1,1-difluoroethyl)-8(S)-(methoxycarbonyl)-2,3,4,5,6(R),7,8,9-octahydro-1H-2,6-methanoazecino[4,3-b]indol-8-yl]-3a(R)-ethyl-5(S)-hydroxy-8-methoxy-6-methyl-3a,4,5,5a(R),6,11,12,12a(R)-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylic acid methyl ester; 4'-Deoxy-20,20'-difluoro-8'-norvincaleukoblastine
CAS No. 162652-95-1
项目整合开发状态: Phase III
项目研究机构: Pierre Fabre (Originator), Bristol-Myers Squibb (Licensee)
合成路线:Fluorination of vinorelbine bitartrate (I) with SbF5 and NBS,NCS,Br2 or Ca(OCl)2 (1),with SbF5 and CCl4 (2,3) or with SbF5 and CHCl3 (3),all in anhydrous HF,gives directly vinflunine (1).Alternatively,fluorination of vinblastine (II) or 3',4'-anhydrovinblastine (III) with SbF5 and CHCl3,2,2-dichloropropane,CBr4,BBr3 or CH2Br2 in anhydrous HF yields 4'-deoxy-20',20'-difluorovinblastine (IV),which is submitted to a C'-ring contraction by treatment with trifluoroacetic acid and NBS in CH2Cl2,then neutralization with NaHCO3 and finally hydrolysis in THF/H2O/CH2Cl2,optionally in the presence of AgBF4 (4).
📌 参考资料/链接:
参考文献标题:Novel antimitotic binary alkaloid derivs.extracted from catharanthus roseus
文献作者:Jacquesy,J.-C.; Fahy,J.; Berrier,C.; Bigg,D.; Jouannetaud,M.-P.; Zunino,F.; Kruczynski,A.; Kiss,R.(Pierre Fabre M閐icament)
参考来源:EP 0710240; FR 2707988; US 5620985; WO 9503312

📄 详细内容


合成路线:Fluorination of vinorelbine bitartrate (I) with SbF5 and NBS,NCS,Br2 or Ca(OCl)2 (1),with SbF5 and CCl4 (2,3) or with SbF5 and CHCl3 (3),all in anhydrous HF,gives directly vinflunine (1).Alternatively,fluorination of vinblastine (II) or 3',4'-anhydrovinblastine (III) with SbF5 and CHCl3,2,2-dichloropropane,CBr4,BBr3 or CH2Br2 in anhydrous HF yields 4'-deoxy-20',20'-difluorovinblastine (IV),which is submitted to a C'-ring contraction by treatment with trifluoroacetic acid and NBS in CH2Cl2,then neutralization with NaHCO3 and finally hydrolysis in THF/H2O/CH2Cl2,optionally in the presence of AgBF4 (4).

参考文献标题:Vinca alkaloid antimitotic halogenated derivs.
文献作者:Duflos,A.; Fahy,J.; Hill,B.; Barret,J.-M.; Thillaye du Boullay,V.(Pierre Fabre M閐icament)
参考来源:EP 0975640; JP 2001518892; US 6127377; WO 9845301


合成路线:Fluorination of vinorelbine bitartrate (I) with SbF5 and NBS,NCS,Br2 or Ca(OCl)2 (1),with SbF5 and CCl4 (2,3) or with SbF5 and CHCl3 (3),all in anhydrous HF,gives directly vinflunine (1).Alternatively,fluorination of vinblastine (II) or 3',4'-anhydrovinblastine (III) with SbF5 and CHCl3,2,2-dichloropropane,CBr4,BBr3 or CH2Br2 in anhydrous HF yields 4'-deoxy-20',20'-difluorovinblastine (IV),which is submitted to a C'-ring contraction by treatment with trifluoroacetic acid and NBS in CH2Cl2,then neutralization with NaHCO3 and finally hydrolysis in THF/H2O/CH2Cl2,optionally in the presence of AgBF4 (4).

参考文献标题:Vinca alkaloids in superacidic media: A method for creating a new family of antitumor derivatives
文献作者:Fahy,J.; et al.
参考来源:J Am Chem Soc 1997,119(36),8576


合成路线:Fluorination of vinorelbine bitartrate (I) with SbF5 and NBS,NCS,Br2 or Ca(OCl)2 (1),with SbF5 and CCl4 (2,3) or with SbF5 and CHCl3 (3),all in anhydrous HF,gives directly vinflunine (1).Alternatively,fluorination of vinblastine (II) or 3',4'-anhydrovinblastine (III) with SbF5 and CHCl3,2,2-dichloropropane,CBr4,BBr3 or CH2Br2 in anhydrous HF yields 4'-deoxy-20',20'-difluorovinblastine (IV),which is submitted to a C'-ring contraction by treatment with trifluoroacetic acid and NBS in CH2Cl2,then neutralization with NaHCO3 and finally hydrolysis in THF/H2O/CH2Cl2,optionally in the presence of AgBF4 (4).

参考文献标题:Fluorination in superacids: A novel access to biologically active compounds
文献作者:Jacquesy,J.-C.; Berrier,C.; Jouannetaud,M.-P.; Zunino,F.; Fahy,J.; Duflos,A.; Ribet,J.-P.
参考来源:J Fluorine Chem 2002,114(2),139


合成路线:Fluorination of vinorelbine bitartrate (I) with SbF5 and NBS,NCS,Br2 or Ca(OCl)2 (1),with SbF5 and CCl4 (2,3) or with SbF5 and CHCl3 (3),all in anhydrous HF,gives directly vinflunine (1).Alternatively,fluorination of vinblastine (II) or 3',4'-anhydrovinblastine (III) with SbF5 and CHCl3,2,2-dichloropropane,CBr4,BBr3 or CH2Br2 in anhydrous HF yields 4'-deoxy-20',20'-difluorovinblastine (IV),which is submitted to a C'-ring contraction by treatment with trifluoroacetic acid and NBS in CH2Cl2,then neutralization with NaHCO3 and finally hydrolysis in THF/H2O/CH2Cl2,optionally in the presence of AgBF4 (4).
参考文献标题:Vinflunine
文献作者:McIntyre,J.A.; Castar,J.
参考来源:Drugs Fut 2004,29(6),574


产品链接: CAS No. 162652-95-1››