Chemo-enzymatic synthesis of rivastigmine intermediate by Locally Isolated Soil Fungus Fusarium graminearum

Abstract

Biocatalytic and bioconversion processes are increasingly playing key roles in the development of pharmaceutical enantiopure drugs. This work describes a process for the production of a key chiral intermediate N-ethyl-N-methyl-carbamic acid-3-(1S-hydroxy-ethyl)-phenyl ester which can be further converted into rivastigmine. (S)-rivastigmine is a chiral drug for the treatment of mild to moderate dementia of Alzheimer’s type. A fungi Fusarium graminearum isolated locally from soil samples was used for regioselective reduction of an acetophenone derivative. The various parameters (pH, temperature, and agitation) of the growth condition were optimized for the culture. The reaction under fermentative condition for 48 hours at a temperature of 30 °C with an agitation speed of 200rpm with 82% final yield was found to be an optimal condition for the overall bioreduction process of the ketone employed in this study. Further, the product is obtained on a gram scale using the selected fungi in a fermentative reduction approach. Biocatalytic and bioconversion processes are increasingly playing key roles in the development of pharmaceutical enantiopure drugs synthesis of rivastigmine intermediate by Locally Isolated Soil Fungus Fusarium graminearum by chemo enzymatic process using the growing organism screening of fungi from soil by plate dilution method, for bior-eduction of specific ketones. The reaction time of 48 h set as optimal because the maximum conversion of the substrate with desired stereo selectivity of 98