| Autor: |
Tang Y; College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA., Dong Y, Wang X, Sriraghavan K, Wood JK, Vennerstrom JL |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of organic chemistry [J Org Chem] 2005 Jun 24; Vol. 70 (13), pp. 5103-10. |
| DOI: |
10.1021/jo050385+ |
| Abstrakt: |
Single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. The complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. To help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4-oxo-TEMPO. Our results suggest a small preference for attack of Fe(II) on the nonketal peroxide oxygen atom of 1. For 4, but not for 5 and 6, there was a strong preference for attack of Fe(II) on the less hindered peroxide bond oxygen atom. The steric hindrance afforded by a spiroadamantane in a five-membered trioxolane is evidently much greater than that for a corresponding six-membered trioxane. Unlike 1, 5-7 fragment by entropically favored beta-scission pathways forming relatively stable alpha-oxa carbon-centered radicals. These data suggest that formation of either primary or secondary carbon-centered radicals is a necessary but insufficient criterion for antimalarial activity of 1 and synthetic peroxides. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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