【药物名称】Vinflunine, L-0070, F-12158, Javlor
化学结构式(Chemical Structure):
参考文献No.26071
标题:Novel antimitotic binary alkaloid derivs. extracted from catharanthus roseus
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)
来源:EP 0710240; FR 2707988; US 5620985; WO 9503312
合成路线图解说明:

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No.37546
标题:Vinca alkaloid antimitotic halogenated derivs.
作者:Duflos, A.; Fahy, J.; Hill, B.; Barret, J.-M.; Thillaye du Boullay, V. (Pierre Fabre M閐icament)
来源:EP 0975640; JP 2001518892; US 6127377; WO 9845301
合成路线图解说明:

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No.685341
标题:Vinca alkaloids in superacidic media: A method for creating a new family of antitumor derivatives
作者:Fahy, J.; et al.
来源:J Am Chem Soc 1997,119(36),8576
合成路线图解说明:

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No.796610
标题:Fluorination in superacids: A novel access to biologically active compounds
作者:Jacquesy, J.-C.; Berrier, C.; Jouannetaud, M.-P.; Zunino, F.; Fahy, J.; Duflos, A.; Ribet, J.-P.
来源:J Fluorine Chem 2002,114(2),139
合成路线图解说明:

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No.816574
标题:Vinflunine
作者:McIntyre, J.A.; Casta馿r, J.
来源:Drugs Fut 2004,29(6),574
合成路线图解说明:

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).

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us