Development of a biocatalytic process for the production of the drug, rasagiline mesylate

摘要

Development of a biocatalytic process for the production of the drug niesilato rasagiline the present invention relates to the development of a biocatalytic process for the synthesis of the drugRasagiline mesylate, used in the treatment monoteru00e1pico of Parkinson's disease in the initial state and as an adjuvant therapy in advanced disease.This drug is a potent propargilamino Inn farmacu00f3foro of segtmda generation that selectively and irreversibly inhibits the enzyme B monoamine oxidase (MAO-B).The enantiu00f4mero configuration (R) is a thousand times more potent than con? Configurations (s).The main strategy in the development of this process includes resolving enzyme kinetics in the presence of serum of the CM - 1 - aminoindano for obtaining the (R) - L - aminoindano,A key intermediate in the synthesis of rasagiline mesylate.The enzyme reaction was carried out by adding the buffer HEPES (PL (7.5), cofator PLP, RAC - L - aminoindano in isopropanol, 4 - hidroxibenzaldeu00eddo and serum ATA - L 13 (Codexis u00ae).The resulting solution remained in the stirring for 24 h at 25 u00b0 C and then raised the pH to 10.After the treatment of the reaction, the crude product was obtained, which was Puri? The chromatography. Ash in the silica gel, leading to the (R) - L - aminoindano, with excess enantiomu00e9rico 99%.Subsequently, the (R) - L - aminoindano was subjected to a reaction of N - alkylation in the presence of propargila chloride, followed by treatment with acid metanossulfu00f4nico,Leading to the production of rasagiline mesylate, with overall yield of 30%.This biocatalytic process is in line with the areas of green chemistry.Since it makes use of a catalyst, biodegradable and suggests a process attractive from an economic point of view, and environmentally friendly.