REGIOSELECTIVE ENZYMATIC SYNTHESIS OF QUERCETIN AND MYRICETIN DERIVATIVES Russian patent published in 2023 - IPC C07D311/32 

FIELD: pharmacy; chemical and pharmaceutical industry.

SUBSTANCE: invention concerns a regioselective method of obtaining esters of flavonoids selected from esters of quercetin or myricetin, and can be used to obtain standard samples and drugs based on these compounds. The proposed method includes the following steps: at the 1st step, quercetin pentabenzoate or myricetin hexabenzoate is obtained at a temperature of 35°C within 1 hour; at the 2nd stage quercetin pentabenzoate or mirecetin hexabenzoate dried at a temperature of 60°C is dissolved in acetonitrile, hydrolyzed only at position 3, which is ensured by heating to 80°C, adding concentrated sulfuric acid, stirring at 200 rpm for 2 hours; at the 3rd stage, esterification is carried out at position 3, neutralizing the medium to pH=6 with a 10% alcoholic solution of potassium hydroxide, using the Novozyme 435 biocatalyst, as acids — either 2-hydroxybenzoic (salicylic) acid, or 4-hydroxybenzoic acid, or 2,6-dihydroxybenzoic acid, or 3,4-dihydroxybenzoic (procatechuic) acid, or 3,4,5-trihydroxybenzoic (gallic) acid, stirring the reaction medium at a speed of 120 rpm at a temperature of 50°C within 6 hours; at the 4th stage, alkaline hydrolysis of blocked hydroxyl groups is carried out using a 10% alcohol solution of potassium hydroxide at a temperature of 70°C for 7 minutes with further neutralization with a 10% sulfuric acid solution, washing with chloroform, recrystallization of the target product at a temperature of -10°C; at the 5th stage, the target product is purified on a column filled with 5 g of silica gel by washing with a mobile phase consisting of a mixture of ethyl acetate-methanol, taken in a volume ratio of 1:9, and drying for 2 hours at a pressure of 25 mm Hg and 60°C.

EFFECT: proposed method makes it possible to obtain esters only at position 3 of quercetin and myricetin, which is achieved by preliminary chemical blocking of all more reactive hydroxyl groups.

1 cl, 10 ex