The compound 5,7-dihydroxy-2-(4-(prop-2-ine-1-eloxy)phenyl)-4hez-chromen-4-one is used as a tracer and targeting agent for antiviral drugs against dengue, Zika, and chikungunya.

Abstract

------07 / 08 / 2568------(OCR) OCR 09WP A compound 5,7-dihydroxy-2-(4-(prop-2-ine-1-eloxy)phenyl)-4H-chromen-4-one, for use as a tracer and target locator for antiviral drugs against dengue, Zika, and chikungunya, as described in this invention, with the following structural formula (chemical formula): which has the property of tracking and locating target proteins and sites of viral infection, can be further developed for tracking other infections or cancer in the future.

Claims

------07 / 08 / 2568------(OCR) OCR 09WP1.

1. The compound 5,7-dihydroxy-2-(4-(prop-2-yne-1-eloxy)phenyl)-4h-chromen-4-one for use as a tracer and target finder for antiviral drugs of dengue, Zika, and chikungunya, with the following structural formula (chemical formula), which has the property of tracking and locating target proteins and sites of viral infection.

2. The procedure for preparing the compound 5,7-dihydroxy-2-(4-(prop-2-yne-1-eloxy)phenyl)-4h-chromen-4-one for use as a tracer and target finder for antiviral drugs of dengue, Zika, and chikungunya according to claim 1, which consists of the following steps: a. Alkylation reaction between... 4-Hydroxybenzaldehyde and Propagyl Bromide (a) Dissolve 4-hydroxybenzaldehyde (300 mg, 2.45 mmol, 1.0 equivalent) and potassium carbonate (1 g, 7.35 mmol, 3.0 equivalent) in acetone (8 ml) while stirring the solution for 30 minutes at room temperature. Slowly drop propagyl bromide (557 µl, 7.35 mmol, 3.0 equivalent) into the solution.0 equivalent) When all the drops are used up, continue stirring the solution under reflux for 4 to 5 hours. Monitor the product with thin-plate chromatography when the reaction is complete and cool to room temperature. Filter out the potassium carbonate. Collect the resulting solution layer. Evaporate the solvent under depressurization to obtain a pale brown solid. Purify by washing with cold hexane to obtain a pale cream solid of 4-(prop-2-in-1-eloxy)benzaldehyde (590 mg, 3.68 mmol, 100%). b. Hydroxy(-OH) shielding reaction using methoxymethyl chloride (MOM-Cl) (b) Dissolve 2,4,6-trihydroxyacetophenone monohydrate (300 mg, 1.78 mmol, 1.0 equivalent) and potassium carbonate (615 mg, 4.45 mmol, 2.5 equivalents) in acetone (8 ml) while stirring the solution for 30 minutes at room temperature. Slowly drop methoxymethyl chloride into the solution, stirring continuously under reflux. Monitor the product with thin-plate chromatography. Once the reaction is complete and the solution has cooled to room temperature, filter out the potassium carbonate. Collect the resulting solution layer. Evaporate the solvent under reduced pressure to obtain a light brown viscous liquid. Purification by column chromatography using silica gel with ethyl acetate and hexane in a ratio of 1:49 to 5:95 as solvent will yield a clear, colorless viscous liquid of 1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)ethane-1-one (91 mg, 0.355 mmol, 20%). c. Aldol condensation reaction between (c) Dissolve 4-(prop-2-ine-1-eloxy)benzaldehyde (114 mg, 0.71 mmol, 2.0 equivalent) in ethanol (1.5 ml). Add a few drops of 1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)ethane-1-one (91 mg, 0.355 mmol, 1.0 equivalent) solution in ethanol (1.5 ml).Stir the mixture at 0°C while slowly adding 50% potassium hydroxide solution (263 µL, 7.1 mmol, 20 equivalents) drop by drop. Continue stirring the mixture at room temperature overnight. Monitor the product using thin-plate chromatography. Upon completion of the reaction, neutralize the resulting solution with 1 M hydrochloric acid solution and extract it three times with 20 ml of ethyl acetate each time. Wash the ethyl acetate fraction three times with 20 ml of water each time, followed by washing it once with 20 ml of saline solution. Dry the obtained ethyl acetate fraction by adding anhydrous magnesium sulfate. Filter out the magnesium. Evaporate the ethyl acetate from the resulting solution under reduced pressure to obtain a viscous yellow liquid. It was purified by column chromatography using silica gel with ethyl acetate, hexane and dichloromethane in a ratio of 8:1:1 as solvents to obtain a yellow solid product of transe-1-(2-hydroxy-4,6-bis(methoxymethoxy)phenyl)-3-(4-prop-2-ine-1-eloxy)phenyl)prop-2-ine-1-one (1) (80 mg, 0.20 mmol, 57%) d. Removal of protective group (d) Dissolve the yellow solid product obtained from step c. (220 mg, 0.55 mmol, 1.The product was reacted with a 15% hydrochloric acid solution in isopropanol at a ratio of 1:5 (33 ml) and stirred at room temperature for 4 to 5 hours. The product was monitored using thin-plate chromatography. Upon completion of the reaction, the resulting solution was neutralized with a saturated sodium bicarbonate solution and extracted with ethyl acetate three times, 40 ml each time. The ethyl acetate fraction was washed with water three times, 40 ml each time, followed by a saline solution once, 20 ml each time. The obtained ethyl acetate fraction was then dried by adding anhydrous sodium sulfate, and the sodium was filtered out. The resulting solution was evaporated from the ethyl acetate under pressure reduction, yielding a yellow solid. This solid was then purified using column chromatography with silica gel, using ethyl acetate and hexane in a ratio of 5:95 to 1:4 as the solvent, resulting in a yellow solid product. Trans-3-(4-prop-2-ine-1-eloxy)phenyl)-1-(2,4,6-trihydroxyphenyl)prop-2-ine-1-one (2) (65 mg, 0.21 mmol, 38%). Cycle reaction (e) Dissolve iodine (0.8 mg, 0.003 mmol, 0.05 Equivalent) in dry dimethyl sulfoxide (454 μL) was dropped into a round-bottom flask containing the yellow solid product obtained from step d (20 mg, 0.064 mmol, 1.The solution was then heated to 90 to 100 °C (equivalent to 00 ml) under a nitrogen gas atmosphere. The solution was stirred at 90 to 100 °C for 6 to 8 hours. The product was monitored using thin-layer chromatography. Once the reaction was complete, water was added at 0 °C to stop the reaction, and the solution was extracted three times with 15 ml of ethyl acetate each time. The ethyl acetate fraction was then washed three times with 15 ml of water each time, followed by one application of sodium thiosulfate solution (20 ml each time). The obtained ethyl acetate fraction was then dried by adding anhydrous sodium sulfate. The sodium was filtered out. The resulting solution was evaporated to remove the ethyl acetate under pressure, yielding a pale yellow solid. This solid was then purified using preparative thin-layer chromatography with ethyl acetate and hexane in a 1:4 ratio as solvents, resulting in a pale yellow solid product. 5,7-dihydroxy-2-(4-(prop-2-in-1-eloxy)phenyl)-4h-chromen-4-one (3) (3.9 mg, 0.13 mmol, 20%) ------------.

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