RCM macrocyclization made practical: an efficient synthesis of HCV protease inhibitor BILN 2061.
Org Lett
; 10(6): 1303-6, 2008 Mar 20.
Article
em En
| MEDLINE
| ID: mdl-18293994
ABSTRACT
We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteases
/
Quinolinas
/
Tiazóis
/
Carbamatos
/
Hepacivirus
/
Compostos Macrocíclicos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article