Betulin glycoconjugates, a method for their preparation and use thereof

Abstract

Betulin glycoconjugates of general formula 3 are characterized in that a betulin derivative of general formula 1, where: R1=OAc, OH, is connected by a linker containing a chain of the O(CO)CH2CH2(CO)OCH2 type and a triazole system, where X=C2HN3, C2HN3CH2CH2O, C2HN3CH2CH2CH2O, with α-D-glycopyranose of general formula 2, where: R2=H, OAc, OBn, R3=H, OAc, OBn, R4=OAc, OBn. The method for the preparation of betulin glycoconjugates of the general formula 3, where: R1=OAc, OH, R2=H, OAc, OBn, R3=H, OAc, OBn, R4=OAc, OBn, X=C2HN3, C2HN3CH2CH2O, C2HN3CH2CH2CH2O, consists in contacting a betulin derivative of the formula 1 in an amount of at least 0.11 mmol with an α-D-glycopyranose derivative of the formula 2, where R2=H, OAc, OBn, R3=H, OAc, OBn, R4=OAc, OBn, R5=N3, OCH2CH2N3, OCH2CH2CH2N3, in a molar ratio ranging from 0.11 mmol to 0.15 mmol 2 / 0.11 mmol 1, in an organic solvent system, preferably in tetrahydrofuran in an amount of 1.0 mL to 1.5 mL THF / 0.11 mmol 1,and in isopropyl alcohol in an amount of 1.0 mL to 1.5 mL of i-PrOH / 0.11 mmol 1, then at room temperature there are added dropwise from 0.7 mL to 1.0 mL of an aqueous solution of copper sulfate in an amount of 16.4 mg to 21 mg of CuSO4 / 0.11 mmol 1 and from 0.7 mL to 1.0 mL of an aqueous solution of sodium ascorbate in an amount of 24 mg to 30 mg of NaASC / 0.11 mmol 1, the whole is stirred at a temperature of 20°C to 35°C for 4 to 7 days, then extracted with organic solvents, preferably dichloromethane, dried with anhydrous MgSO4, the solvent is evaporated under reduced pressure from 10 mmHg to 40 mmHg, preferably 20 mmHg, and then the product is purified by the method Column chromatography. Use of betulin glycoconjugates in the production of pharmaceuticals intended to inhibit the proliferation of breast cancer cells.