Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR.
Bioorg Med Chem Lett
; 23(21): 5865-9, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-24055047
ABSTRACT
The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (-)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alcaloides de Vinca
/
Vincamina
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article