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...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1477-0520
1477-0539
DOI:10.1039/c2ob25212k