Abstract
Novel C-17-chloro-substituted derivative of vinorelbine or vinflunine has been regio-selectively synthesized via the chlorination reaction in the presence of Lewis acid. The catalyst Cp2TiCl2 plays a key role in the chlorination reaction.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aapro MS, Harper P, Johnson SA, Vermorken JB. Developments in cytotoxic chemotherapy: Advances in treatment utilising vinorelbine. Critical Rev Oncology Hematology, 2001, 40: 251–263
Checchi PM, Nettles JH, Zhou J, Snyder JP, Joshi HC. Microtubule-interacting drugs for cancer treatment. Trends Pharmacol Sci, 2003, 24: 361–365
Gigant B, Wang C, Ravelli RBG, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M. Structural basis for the regulation of tubulin by vinblastine. Nature, 2005, 435: 519–522
Sasaki Y, Kato D, Boger DL. Asymmetric total synthesis of vindorosine, vindoline, and key vinblastine analogues. J Am Chem Soc, 2010, 132: 13533–13544
Ishikawa H, Colby DA, Boger DL. Direct coupling of catharanthine and vindoline to provide vinblastine: Total synthesis of (+)- and ent-(−)-vinblastine. J Am Chem Soc, 2008, 130: 420–421
Miyazaki T, Yokoshima S, Simizu S, Osada H, Tokuyama H, Fukuyama T. Synthesis of (+)-vinblastine and its analogues. Org Lett, 2007, 9: 4737–4740
Yokoshima S, Ueda T, Kobayashi S, Sato A, Kuboyama T, Tokuyama H, Fukuyama T. Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc, 2002, 124: 2137–2139
Tam A, Gotoh H, Robertson WM, Boger DL. Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: Preparation and evaluation of a key series of vinblastine analogues. Bioorg Med Chem Lett, 2010, 20: 6408–6410
Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guenard D, Gueritte F. Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids. J Med Chem, 2009, 52: 134–142
Passarella D, Giardini A, Peretto B, Fontana G, Sacchetti A, Silvani A, Ronchi C, Cappelletti G, Cartelli D, Borlak J, Danieli B. Inhibitors of tubulin polymerization: Synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III. Bioorg Med Chem, 2008, 16: 6269–6285
Shao Y, Ding H, Tang W, Lou L, Hu L. Synthesis and structure-activity relationships study of novel anti-tumor carbamate anhydrovinblastine analogues. Bioorg Med Chem, 2007, 15: 5061–5075
Kuehne ME, Bornmann WG, Marko I, Qin Y, LeBoulluec KL, Frasier DA, Xu F, Mulamba T, Ensinger CL, Borman LS, Huot AE, Exon C, Bizzarro FT, Cheung JB, Bane SL. Syntheses and biological evaluation of vinblastine congeners. Org Biomol Chem, 2003, 1: 2120–2136
Danieli B, Lesma G, Martinelli M, Passarella D, Silvani A. Vinblastine-type antitumor alkaloids: A method for creating new C17 modified analogues. J Org Chem, 1998, 63: 8586–8588
Mangeney P, Andriamialisoa RZ, Langlois N, Langlois Y, Potier P. A new class of antitumor compounds: 5′-Nor and 5′,6′-seco derivatives of vinblastine-type alkaloids. J Org Chem, 1979, 44: 3765–3768
Potier P. Synthesis of the antitumor dimeric indole alkaloids from catharanthus species (vinblastine group). J Nat Prod, 1980, 43:72–86
Conrad RA, Cullinan GJ, Gerzon K, Poore GA. Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted deacetylvinblastine amide (vindesine) sulfates. J Med.Chem, 1979, 22: 391–400
Langlois N, Gueritte F, Langlois Y, Potier P. Application of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloids. J Am Chem Soc, 1976, 98: 7017–7024
Pearce HL. 12′-Iodo derivatives of dimeric indole-dihydroindole alkaloids, and process for preparing them. US Patent 4430269, 1984-02-07; Chem Abstr, 1984, 100: 192142
Lu Y, Shi T, Wang Y, Yang H, Yan X, Luo X, Jiang H, Zhu W. Halogen bonding: A novel interaction for rational drug design? J Med Chem, 2009, 52: 2854–2862
Jacquesy JC. Reactivity of Vinca alkaloids in superacid: An access to vinflunine, a novel anticancer agent. J Fluorine Chem, 2006, 127: 1484–1487
Fahy J, Boullay VT, Bigg DCH. New method of synthesis of vinca alkaloid derivatives. Bioorg Med Chem Lett, 2002, 12: 505–507
Jacquesy JC, Berrier C, Jouannetaud MP, Zunino F, Fahy J, Duflos A, Ribet JP. Fluorination in superacids: A novel access to biologically active compounds. J Fluorine Chem, 2002, 114: 139–141
Lafitte C, Jouannetaud MP, Jacquesy JC, Fahy J, Duflos A. Stereoselective ionic hydrogenation of vinca alkaloids and vinorelbine in superacids: An access to 4′R-reduced analogs. Tetrahedron Lett, 1998, 39: 8281–8282
Fahy J, Duflos A, Ribert JP, Jacquesy JC, Berrier C, Jouannetaud MP, Zunino F. Vinca alkaloids in superacidic media: A method for creating a new family of antitumor derivatives. J Am Chem Soc, 1997, 119: 8576–8577
Lei XS, Yu XD, Yin L, Liu ZH, Tang PC. Synthesis and biological evaluation of C-12′ substituted vinflunine derivatives. Bioorg Med Chem Lett, 2008, 18: 4602–4605
Voss ME, Ralph JM, Xie D, Manning DD, Chen X, Frank AJ, Leyhane AJ, Liu L, Stevens JM, Budde C, Surman MD, Friedrich T, Peace D, Scott IL, Wolf M, Johnson R. Synthesis and SAR of vinca alkaloid analogues. Bioorg Med Chem Lett, 2009, 19: 1245–1249
Ribet JP, Zalavari P, Fahy J, Duflos A, Beltran T. Complete assignment of 1H and 13C NMR spectra of vinflunine. Magn Reson Chem, 2001, 39: 43–48
Ribet JP, Zalavari P, Commenges G, Fahy J, Duflos A, Schambel P. Analyse structurale de la vinorelbine en solution determinee par spectrometrie de resonance magnetique nucleaire. Ann Pharmaceutiques Francaises, 1997, 55: 20–34
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fang, L., Zhang, Q., Deng, C. et al. Regio-selective chlorination of vinca alkaloids catalyzed by Lewis acid. Sci. China Chem. 54, 1039–1043 (2011). https://doi.org/10.1007/s11426-011-4310-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11426-011-4310-2