Biotransformation of Colchicinoids into Their Corresponding 3-O-Glucosyl Derivatives by Selected Strains of Bacillus megaterium |
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Authors: | Cesare Ponzone Davide Berlanda Fabio Donzelli Valter Acquati Rosalba Ciulla Alberto Negrini Marco Rovati Douglas Evangelista Emilio Fata Daniele Ciceri Federico Perterlongo Walter Cabri |
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Affiliation: | 1. Indena S.p.A., Via Don Minzoni, 6, Settala, 20090, Milan, Italy 2. Indena S.p.A., Viale Ortles 12, 20139, Milan, Italy
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Abstract: | Natural colchicinoids and their semisynthetic derivatives are important active ingredients for pharmaceutical applications. Thiocolchicoside (3-demethoxy-3-glucosyloxythiocolchicine) is used in several countries as standard therapy for the treatment of diseases of the muscle–skeletal system, due to its potent antiinflammatory and myorelaxant properties. Manufacturing of thiocolchicoside requires a key step, the regioselective demethylation and glucosylation of chemically derivative thiocolchicine. High selectivity and efficiency of this transformation cannot be achieved in a satisfactory way with a chemical approach. In particular, the chemical demethylation, a part from requiring toxic and aggressive reagents, generates a complex mixture of products with no industrial usefulness. We report herein an efficient, direct and green biotransformation of thiocolchicine into thiocolchicoside, performed by a specific strain of Bacillus megaterium. The same process, with minor modifications, can be used to convert the by-product 3-O-demethyl-thiocolchicine into thiocolchicoside. In addition, we describe the B. megaterium strain selection process and the best conditions for this effective double biotransformation. The final product has a pharmaceutical quality, and the process has been industrialised. |
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