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.
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.
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.
