title: Biomimetic oxidation of aromatic xenobiotics: synthesis of the phenolic metabolites from the anti-HIV drug efavirenz.
abstract: 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.
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, 1049-001, Lisboa, Portugal. riccardowanke@ist.utl.pt
authors.forename: Riccardo
authors.initials: R
authors.lastname: Wanke
authors.forename: David A
authors.initials: DA
authors.lastname: Novais
authors.forename: Shrika G
authors.initials: SG
authors.lastname: Harjivan
authors.forename: M Matilde
authors.initials: MM
authors.lastname: Marques
authors.forename: Alexandra M M
authors.initials: AM
authors.lastname: Antunes
mesh_terms: D000480:Alkynes; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry*; D048588:Benzoxazines / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry*; D003521:Cyclopropanes; D006736:Horses; D015394:Molecular Structure; D010084:Oxidation-Reduction; D019800:Phenol / Q000737:chemistry* / Q000378:metabolism; D015262:Xenobiotics / Q000737:chemistry*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015262:Xenobiotics; D019800:Phenol; C098320:efavirenz