Synthesis of tricyclic benzimidazole-iminosugars as potential glycosidase inhibitors via a Mitsunobu reaction.
Carbohydr Res
; 485: 107807, 2019 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-31520817
ABSTRACT
A series of tricyclic benzimidazole-iminosugars 1(a-f) and 2(a-f) were synthesized and evaluated for their their inhibitory activities against five glycosidases. The synthesis initiated from the benzyl protected sugar (aldehyde) 5 that reacted with 1,2-diaminobenzene to afford aldo-benzimidazole 6 by the iodine-induced oxidative condensation. Then, tricyclic compound 7 was obtained in high yields of 73%-87% by the key Mitsunobu reaction through intramolecular cyclization of the unprotected OH and the NH in 6. After removal of the benzyl group in CF3SO3H, the target tricyclic benzimidazole-iminosugars 1 and 2 were achieved. The protocol was effective for the preparation of the tricyclic iminosugar in satisfactory yield. The results of the glycosidase inhibitory activities of 1 and 2 showed that three compounds derived from d-ribose exhibited specific and good inhibitory effects on ß-glucosidase. Among them, 1e-1 was the best one with IC50 value of 5.37⯵M. All hydroxyl groups on ß-position would be favourable to the inhibitory activity of such tricyclic benzimidazole-iminosugars against ß-glucosidase.
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MEDLINE
Assunto principal:
Benzimidazóis
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Inibidores Enzimáticos
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Imino Açúcares
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Glicosídeo Hidrolases
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article