Biomimetic oxidation studies of monensin A catalyzed by metalloporphyrins: identification of hydroxyl derivative product by electrospray tandem mass spectrometry

Author(s)

José N. Sousa-Junior ^[1] ; Bruno A. Rocha ^[2] ; Marilda D. Assis ^[2] ; Ana P. F. Peti ^[2] ; Luiz A. B. Moraes ^[2] ; Yassuko Iamamoto ^[2] ; Paul J. Gates ^[3] ; Anderson R. M. de Oliveira ^[2] ; Norberto P. Lopes ^[4]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Ciêcias Farmacêuticas. Departamento de Física e Química - Brasil

^[2] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Bristol, Sch Chem, Bristol, Avon - England

^[4] Univ Sao Paulo, Nucleo Pesquisas Prod Nat & Sintet, Fac Ciencias Farmaceut, Dept Fis & Quim, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY; v. 23, n. 4, p. 621-629, 2013-08-09.

Abstract

Monensin A is an important commercially available natural product isolated from Streptomyces cinnamonensins that shows antibiotic and anti-parasitic activities. This molecule has a significant influence in the antibiotic market, but until now there are no studies on putative metabolite formations. Bioorganic catalysts applying metalloporphyrins and mono-oxygen donors are able to mimic the cytochrome P450 reactions. This model has been employed for natural product metabolism studies affording several new putative metabolites and in vivo experiments confirming the relevance of this procedure. In this work we evaluated the potential of 10,15,20-tetrakis (pentafluorophenyl) porphyrin metal(III) chloride [Fe(TFPP)Cl] catalyst models to afford a putative monensin A metabolite. Oxidation agents such as meta-chloroperoxy benzoic acid, iodosylbenzene, hydrogen peroxide 30 wt.% and tert-butyl hydroperoxide 70 wt.%, were used to investigate different reaction conditions, in addition to the analysis of the influence of the solvent. The quantification of total monensin A conversion and the structure of the new hydroxylated putative metabolite were proposed based on electrospray ionization tandem mass spectrometry analysis. The porphyrin tested, afforded moderate conversions of monensin A in all reaction conditions and the selectivity was found to be dependent on the oxidation/medium employed. (AU)

• FAPESP's process: 11/05800-0 - Evaluation of Microbiological and Chemical Models for the Study of Bio(transformations) of Antibiotic Monensin A
• Grantee: Bruno Alves Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate