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.

Ponzone, C., Berlanda, D., Donzelli, F., et al. (2014). 100- “Biotransformation of Colchicinoids into Their Corresponding 3-O-Glucosyl Derivatives by Selected Strains of Bacillus megaterium. MOLECULAR BIOTECHNOLOGY, 56, 653-659 [10.1007/s12033-014-9741-5].

100- “Biotransformation of Colchicinoids into Their Corresponding 3-O-Glucosyl Derivatives by Selected Strains of Bacillus megaterium

Cabri W
2014

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.
2014
Ponzone, C., Berlanda, D., Donzelli, F., et al. (2014). 100- “Biotransformation of Colchicinoids into Their Corresponding 3-O-Glucosyl Derivatives by Selected Strains of Bacillus megaterium. MOLECULAR BIOTECHNOLOGY, 56, 653-659 [10.1007/s12033-014-9741-5].
Ponzone; C.; Berlanda; D.; Donzelli; F.; Acquati; V.; Ciulla; R.; Negrini; A.; Rovati; M.; Evangelista; D.; Fata; E.; Ciceri; D.; Perterlongo; F.; Cabri W
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/756752
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