METHOD OF OBTAINING PHOTOSENSITIZER FOR PHOTODYNAMIC DESTRUCTION OF TUMOR CELLS Russian patent published in 2023 - IPC C07D257/08 C07D309/02 

FIELD: organic and pharmaceutical chemistry.

SUBSTANCE: invention relates to a method of producing an organic compound for the photodynamic destruction of tumor cells. A method of producing a photosensitizer for the photodynamic destruction of tumor cells with the specified structural formula is disclosed, the said method includes the interaction of 1 molar equivalent of (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(2-azidoethoxy)tetrahydro-2H-pyran- 3,4,5-triyl triacetate with 1 molar equivalent of 6-(4-ethynylphenyl)-1-(1-(4-nitrophenyl)ethyl)-2,4-diphenyl-1,4-dihydro-1,2,4,5-tetrazin-3(2H)-one in a deoxygenated mixture of tetrahydrofuran and water, obtained at a ratio of 6:3 ml per 1 mmol (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-( 2-azidoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate in the presence of 0.8 molar equivalents of sodium ascorbate and 0.4 molar equivalents of copper (II) sulfate at a temperature of 70°C with constant stirring in an argon atmosphere for 2 hours, after which the reaction mass is cooled to room temperature, the solvent is removed in vacuo, the residue is dissolved in water and extracted with ethyl acetate, the organic layer is separated, dried using anhydrous magnesium sulfate and then evaporated, the product reactions are isolated by column chromatography on silica gel using hexane and ethyl acetate, then 1 molar equivalent of the resulting product is dissolved in 100 ml of anhydrous methanol per 1 mmol of tetraacetate 1-(1-(4-nitrophenyl)ethyl)-2,4-diphenyl-6-(4-(1-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)phenyl)-1,4-dihydro-1,2,4,5-tetrazin-3(2H)-one and add 1.5 molar equivalents of sodium methoxide, stir at room temperature for 2 hours, the pH of the solution is adjusted to 7 using an ion exchange resin, then the solution is filtered from the ion exchange resin, the resin on the filter is washed with methanol 3 times and the combined methanol solution is evaporated to dryness in vacuum on a rotary evaporator, the target product is isolated by column chromatography on silica gel using dichloromethane and methanol, resulting in 1-(1-(4-nitrophenyl)ethyl)-2,4-diphenyl-6-(4-(1-(2-(((2R,3R,4S, 5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-1,2,3-triazol-4-yl)phenyl)- 1,4-dihydro-1,2,4,5-tetrazin-3(2H)-one with the general formula C₄₄H₄₄N₈O₁₂.

EFFECT: invention provides a new photosensitizer that exhibits cytotoxic activity when exposed to light with a wavelength of 395–410 nm for 20 minutes, and its solubility in an aqueous solution is 400 μM.

1 cl, 1 dwg, 1 ex