Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz

We report the oxidation of the first line anti-HIV drug efavirenz (EFV), mediated by a bio-inspired nonheme Fe-complex. Depending upon the experimental conditions this system can be tuned either to yield the major EFV metabolite, 8-hydroxy-EFV, in enantiomerically pure form or to mimic cytochrome P4...

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Published in:Organic & biomolecular chemistry 2012-06, Vol.1 (23), p.4554-4561
Main Authors: Wanke, Riccardo, Novais, David A, Harjivan, Shrika G, Marques, M. Matilde, Antunes, Alexandra M. M
Format: Article
Language:English
Subjects:
Animals
Anti-HIV Agents - chemistry
Benzoxazines - chemistry
Biomimetic Materials - chemistry
Horses
Human immunodeficiency virus
Molecular Structure
Oxidation-Reduction
Phenol - chemistry
Phenol - metabolism
Xenobiotics - chemistry
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cited_by cdi_FETCH-LOGICAL-c368t-77e60b81888e92f53a4e7433e1027925ae31e118e0424c07e84adf961b1175723
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creator Wanke, Riccardo
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description We report the oxidation of the first line anti-HIV drug efavirenz (EFV), mediated by a bio-inspired nonheme Fe-complex. Depending upon the experimental conditions this system can be tuned either to yield the major EFV metabolite, 8-hydroxy-EFV, in enantiomerically pure form or to mimic cytochrome P450 (CYP) activity, yielding 8-hydroxy-EFV and 7-hydroxy-EFV, the two phenolic EFV metabolites reported to be formed in vivo . The successful oxidation of the anti-estrogen tamoxifen and the equine estrogen equilin into their CYP-mediated metabolites supports the general application of bio-inspired nonheme Fe-complexes in mirroring CYP activity. We report the oxidation of efavirenz, equilin and tamoxifen by a bio-inspired Fe-complex, yielding the phenolic metabolites of these xenobiotics.
doi_str_mv 10.1039/c2ob25212k
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source Royal Society of Chemistry
subjects Animals
Anti-HIV Agents - chemistry
Benzoxazines - chemistry
Biomimetic Materials - chemistry
Horses
Human immunodeficiency virus
Molecular Structure
Oxidation-Reduction
Phenol - chemistry
Phenol - metabolism
Xenobiotics - chemistry
title Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz
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