| Autor: |
Somsak, L., Kovacs, L., Toth, M., Osz, E., Szilagyi, L., Gyorgydeak, Z., Dinya, Z., Docsa, T., Toth, B., Gergely, P. |
| Zdroj: |
Journal of Medicinal Chemistry; August 2001, Vol. 44 Issue: 17 p2843-2848, 6p |
| Abstrakt: |
d-Gluco- and d-xylopyranosylidene-spiro-hydantoins and -thiohydantoins were prepared from the parent sugars in a six-step, highly chemo-, regio-, and stereoselective procedure. In the key step of the syntheses C-(1-bromo-1-deoxy-β-d-glycopyranosyl)formamides were reacted with cyanate ion to give spiro-hydantoins with a retained configuration at the anomeric center as the major products. On the other hand, thiocyanate ions gave spiro-thiohydantoins with an inverted anomeric carbon as the only products. On the basis of radical inhibition studies, a mechanistic rationale was proposed to explain this unique stereoselectivity and the formation of C-(1-hydroxy-β-d-glycopyranosyl)formamides as byproducts. Enzyme assays with a and b forms of muscle and liver glycogen phosphorylases showed spiro-hydantoin 12 and spiro-thiohydantoin 14 to be the best and equipotent inhibitors with Ki values in the low micromolar range. The study of epimeric pairs of d-gluco and d-xylo configurated spiro-hydantoins and N-(d-glucopyranosyl)amides corroborated the role of specific hydrogen bridges in binding the inhibitors to the enzyme. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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