Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: asymmetric glycolate aldol reactions and biological evaluation.
J Org Chem
; 68(21): 8162-9, 2003 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-14535799
ABSTRACT
The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 101 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.
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Base de dados:
MEDLINE
Assunto principal:
Quinonas
/
Aldeídos
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos