BIOCONVERSION OF INHOFFEN-LYTHGOE’S DIACETATE BY FUSARIUM VERTICILLIOIDES

ACIAR R, ALLENDES J, RAVETTI S, ROSA M, SANTANDREU N, BUSTOS D, MOURIÑO A, BUSTOS DA

Córdoba, Argentina

Otro; Primera Reunión Internacional de Ciencias Farmacéuticas; 2010

Departamento de Farmacia de Facultad de Ciencias Químicas de la Universidad Nacional de Córdoba y Departamento de Farmacia de Facultad de Ciencias Bioquímicas y Farmacéuticas de la Universidad Nacional de Rosario

Biotransformations are a good example of ability of microorganisms to change one of several functional groups with similar reaction properties or to functionalize low reactive positions in organic compounds through enzymatic reactions, allowing to obtain novel compounds with potential biological activity. During last years both in industry and in pharmaceutical chemistry innovation and productivity of drugs is one of the most important processes, which is done by chemical synthesis, semi-synthesis or by harmless biotechnological procedures known as biotransformation or bioconversion that involve the use of microorganisms. This technique include oxidation-reduction modifications, rearrangement, opening or ring closure, C-C bond formation, addition-elimination, racemic mixture resolution, among others. Besides microorganisms can be used as a model of mammalian metabolism, allowing to predict and prepare metabolites related to drugs administered to animals and humans. This methodology has permitted to obtain a wide variety of products of high value added so the aim of this work is about biotransformation the substrate, the diol of Inhoffen-Lythgoe which is related to some portion of vitamin D and has two rings. Nowadays biotechnology is applied to several areas. Looking for the best biocatalysts and using new technologies to keep competitive and innovative pharmaceutical industries obtain active drugs economically attractive so that quiral intermediates are an important task of fine chemical market, showed by the increased claim of these products. Biotransformation was carried out using the filamentous fungus Fusarium verticillioides, which has the capability to hydroxylate several compounds.This process was done using liquid culture medium and appropriate conditions for microorganism growth, followed by preparative scale under the same conditions as preliminary screening. Several metabolites were obtained and two of them in higher amounts which were isolated by chromatographic techniques. This derivatives as well as starting material were identified using besides classical spectroscopic methods, NMR techniques like homo and heteronuclear COSY, DEPT and IR. Those spectra were compared with substrate spectrum and hydroxyl group signals in different positions were found. In structures of metabolites close related to calcitriol has been found that modifications of the cyclopentane ring side chain have incidence on the selectivity to biological response of physiological functions related to calcium and phosphorous homeostasis processes.3 So it is expected this compounds shows a higher biological activity as a consequence of changes on chemical structure. Several metabolites were obtained and two of them in higher amounts which were isolated by chromatographic techniques. This derivatives as well as starting material were identified using besides classical spectroscopic methods, NMR techniques like homo and heteronuclear COSY, DEPT and IR. Those spectra were compared with substrate spectrum and hydroxyl group signals in different positions were found. In structures of metabolites close related to calcitriol has been found that modifications of the cyclopentane ring side chain have incidence on the selectivity to biological response of physiological functions related to calcium and phosphorous homeostasis processes.3 So it is expected this compounds shows a higher biological activity as a consequence of changes on chemical structure. Several metabolites were obtained and two of them in higher amounts which were isolated by chromatographic techniques. This derivatives as well as starting material were identified using besides classical spectroscopic methods, NMR techniques like homo and heteronuclear COSY, DEPT and IR. Those spectra were compared with substrate spectrum and hydroxyl group signals in different positions were found. In structures of metabolites close related to calcitriol has been found that modifications of the cyclopentane ring side chain have incidence on the selectivity to biological response of physiological functions related to calcium and phosphorous homeostasis processes.3 So it is expected this compounds shows a higher biological activity as a consequence of changes on chemical structure.