(7S) -3,4-Dimethoxybicyclo [4.2.0] enzymatic synthesis method of octa-1,3,5-triene-7-carboxylic acid and application in the synthesis of ivabradine and its salts
Synthesizing (7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid compound (I), comprises enantioselective enzymatic hydrolysis of 3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile compounds (IV), using the nitrilase of Rhodococcus rhodochrous NCIMB 11216 over expressed in another organism having a competent biological system, in a mixture of an organic solvent and an aqueous solution having a pH of 5-10, at a concentration of 1-500 g of (IV) per liter of solvent mixture, at a ratio of an enzyme/substrate (IV) of 1:1-1:100, and at a temperature of 25-40[deg] C. Synthesizing (7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid compound of formula (I) or its enantiomer, comprises enantioselective enzymatic hydrolysis of racemic or not optically pure 3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carbonitrile compounds of formula (IV), using the nitrilase of Rhodococcus rhodochrous NCIMB 11216 over expressed in another organism having a competent biological system, in a mixture of an organic solvent and an aqueous solution having a pH of 5-10, at a concentration of 1-500 g of (IV) per liter of solvent mixture, at a ratio of an enzyme/substrate (IV) of 1:1-1:100, and at a temperature of 25-40[deg] C. An independent claim is included for synthesizing ((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl-methyl)-methyl-amine compound (III) or its enantiomer, comprising hydrolyzing (IV) to form (I), and then converted into (S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-carboxylic acid methylamide compound (xx) and reducing which yields of (III). [Image] ACTIVITY : Cardiant； Vasotropic； Antianginal. MECHANISM OF ACTION : None given.
