38390-45-3Relevant articles and documents
Preparation method of vinorelbine tartrate
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Paragraph 0078-0085; 0104-0111, (2021/03/30)
The invention discloses a preparation method of vinorelbine tartrate, which comprises the following steps: 1) preparation of dehydrated vinblastine: taking vinblastine sulfate and vindoline as initialraw materials, and carrying out ferric trichloride catalysis and sodium borohydride reduction to obtain dehydrated vinblastine; 2) preparation of bromo-dehydrated vinblastine: carrying out bromination reaction on dehydrated vinblastine and N-bromo-succinimide to obtain a bromo-dehydrated vinblastine crude product; carrying out column purification on the bromo-dehydrated vinblastine crude productto improve the purity of the bromo-dehydrated vinblastine crude product so as to obtain bromo-dehydrated vinblastine; 3) preparation of vinorelbine: carrying out debromination rearrangement on bromo-dehydrated vinblastine and a silver tetrafluoroborate aqueous solution to obtain a vinorelbine crude product; and recrystallizing the vinorelbine crude product to obtain a vinorelbine pure product; and4) preparation of vinorelbine tartrate: carrying out a salt forming reaction on the pure vinorelbine tartrate and tartaric acid to obtain vinorelbine tartrate. The method has the advantages of simpleoperation, few side reactions, great increase of the purity and the yield, reduction of the production cost, and suitableness for large-scale production.
Triarylaminium Radical Cation Promoted Coupling of Catharanthine with Vindoline: Diastereospecific Synthesis of Anhydrovinblastine and Reaction Scope
Boon, Byron A.,Boger, Dale L.
supporting information, p. 14349 - 14355 (2019/10/11)
A new triarylaminium radical cation promoted coupling of catharanthine with vindoline is disclosed, enlisting tris(4-bromophenyl)aminium hexachlororantimonate (BAHA, 1.1 equiv) in aqueous 0.05 N HCl/trifluoroethanol (1-10:1) at room temperature (25 °C), that provides anhydrovinblastine in superb yield (85%) with complete control of the newly formed quaternary C16′ stereochemistry. A definition of the scope of aromatic substrates that participate with catharanthine in the BAHA-mediated diastereoselective coupling reaction and simplified indole substrates other than catharanthine that participate in the reaction are disclosed that identify the key structural features required for participation in the reaction, providing a generalized indole functionalization reaction that bears little structural relationship to catharanthine or vindoline.
Vinblastine 20′ Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance
Lukesh, John C.,Carney, Daniel W.,Dong, Huijun,Cross, R. Matthew,Shukla, Vyom,Duncan, Katharine K.,Yang, Shouliang,Brody, Daniel M.,Brütsch, Manuela M.,Radakovic, Aleksandar,Boger, Dale L.
, p. 7591 - 7604 (2017/09/22)
A series of 180 vinblastine 20′ amides were prepared in three steps from commercially available starting materials, systematically exploring a typically inaccessible site in the molecule enlisting a powerful functionalization strategy. Clear structure-activity relationships and a structural model were developed in the studies which provided many such 20′ amides that exhibit substantial and some even remarkable enhancements in potency, many that exhibit further improvements in activity against a Pgp overexpressing resistant cancer cell line, and an important subset of the vinblastine analogues that display little or no differential in activity against a matched pair of vinblastine sensitive and resistant (Pgp overexpressing) cell lines. The improvements in potency directly correlated with target tubulin binding affinity, and the reduction in differential functional activity against the sensitive and Pgp overexpressing resistant cell lines was found to correlate directly with an impact on Pgp-derived efflux.
Synthesis and antiproliferativeactivity of new vinca alkaloids containing an α,β-unsaturated aromatic side chain
Ngo, Quoc Anh,Nguyen, Le Anh,Vo, Ngoc Binh,Nguyen, Thuy Hang,Roussi, Fanny,Nguyen, The Hung,Nguyen, Van Tuyen
, p. 5597 - 5600 (2015/11/17)
A new series of vinca-alkaloids derivatives containing various α,β-unsaturated aromatic side chains was synthesized. Four new vinca-alkaloids derivatives showed selective cytotoxicities against KB tumor cell lines with IC50 value below 0.1 μM, thus comparable with vinblastine.
New insights into the mechanism and an expanded scope of the Fe(III)-mediated vinblastine coupling reaction
Gotoh, Hiroaki,Sears, Justin E.,Eschenmoser, Albert,Boger, Dale L.
supporting information; experimental part, p. 13240 - 13243 (2012/09/22)
A definition of the scope of aromatic substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examination of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addition to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aqueous buffer may be radical mediated, the studies provide new opportunities for the preparation of previously inaccessible vinblastine analogs and define powerful new methodology for the synthesis of indole-containing natural and unnatural products.
10′-fluorovinblastine and 10′-fluorovincristine: Synthesis of a key series of modified vinca alkaloids
Gotoh, Hiroaki,Duncan, Katharine K.,Robertson, William M.,Boger, Dale L.
scheme or table, p. 948 - 952 (2012/02/01)
A study on the impact of catharanthine C10 and C12 indole substituents on the biomimetic Fe(III)-mediated coupling with vindoline led to the discovery and characterization of two new and substantially more potent derivatives, 10′-fluorovinblastine and 10′-fluorovincristine. In addition to defining a pronounced and unanticipated substituent effect on the biomimetic coupling, fluorine substitution at C10′, which minimally alters the natural products, was found to uniquely enhance the activity 8-fold against both sensitive (IC50 = 800 pM, HCT116) and vinblastine-resistant tumor cell lines (IC50 = 80 nM, HCT166/VM46). As depicted in the X-ray structure of vinblastine bound to tubulin, this site resides at one end of the upper portion of the T-shaped conformation of the tubulin-bound molecule, suggesting that the 10′-fluorine substituent makes critical contacts with the protein at a hydrophobic site uniquely sensitive to steric interactions.
Synthesis of anti-tumor dimeric indole alkaloids in catharanthus roseus was promoted by irradiation with near-ultraviolet light at low temperature
Asano, Mamiko,Harada, Kazuo,Yoshikawa, Tomoaki,Bamba, Takeshi,Hirata, Kazumasa
body text, p. 386 - 389 (2010/10/03)
We have found that coupling between catharanthine and vindoline occurs non-enzymatically in the presence of flavin mononucleotide and manganese ions with near- ultraviolet light irradiation in vitro. The present study found that the concentrations of cath
Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: Preparation and evaluation of a key series of vinblastine analogues
Tam, Annie,Gotoh, Hiroaki,Robertson, William M.,Boger, Dale L.
supporting information; scheme or table, p. 6408 - 6410 (2010/12/18)
The examination of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 methyl ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16′ methyl ester with an ethyl ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold) or a primary carboxamide (>1000-fold) led to surprisingly large reductions in cytotoxic activity.
Process for the preparation of bisindole alkaloid derivatives
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Page/Page column 6, (2009/12/28)
A process for the coupling of catharantine and vindoline catalyzed by Laccases is described. The coupling produces anhydrovinblastine and anhydrovinblastine eniminium, which can be transformed to vinblastine or vinorelbine.
Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids
Ngo, Quoc Anh,Roussi, Fanny,Cormier, Anthony,Thoret, Sylviane,Knossow, Marcel,Guenard, Daniel,Gueritte, Frangoise
scheme or table, p. 134 - 142 (2009/09/06)
Ten hybrids of vinca alkaloids and phomopsin A have been synthesized by linking the octahydrophomopsin lateral chain to the tertiary amine of the cleavamine moiety of anhydrovinblastine (AVLB) and vinorelbine. These compounds have been elaborated in order
