Method for preparing diselenide compound

Abstract

The present disclosure provides a method for preparing diselenide compound. A polar solvent is added to a dihydroflavonol compound, heated to 80° C.˜100° C., kept for 40˜50 minutes, then the base in the amount of 0.4˜1.0 times the amount of the dihydroflavonol compound is added and reacted at 80° C.˜100° C. for 5˜60 minutes, then selenium dioxide in the amount of 0.6˜1.2 times the amount of dihydroflavonol compounds at 80° C.˜100° C. The diselenide compound of the dihydroflavonol compound is obtained by reacting at a temperature of 80° C.˜100° C. for 30˜150 minutes. The method of the present disclosure has mild reaction, low pollution, does not require an anhydrous and oxygen-free environment, and is suitable for large-scale industrial production.

Claims

1. A method for preparing a diselenide compound of a dihydrofalvonol compound, comprising steps of: adding polar solvent to dihydroflavonol compound, heating to 80° C.˜100° C., and keeping for 40˜50 minutes; then adding base in the amount of 0.4˜1.0 times the amount of the dihydroflavonol compound, reacting for 5˜60 minutes at a temperature of 80° C.˜100° C.; then adding selenium dioxide in the amount of 0.6˜1.2 times the amount of the dihydroflavonol compound, reacting for 30˜150 minutes at a temperature of 80° C.˜100° C.; and obtaining the diselenide compound of the dihydroflavonol compound.

2. The method for preparing the diselenide compound according to claim 1, wherein the dihydroflavonol compound is of the following formula: ##STR00013## wherein R.sub.1 is —H, —OH, CH.sub.3O—, CH.sub.3CH.sub.2O—, (CH.sub.3).sub.3CO—, C.sub.6H.sub.6CH.sub.2O—, or a glycoside; R.sub.2 is —H, —OH, CH.sub.3O—, CH.sub.3CH.sub.2O—, (CH.sub.3).sub.3CO—, C.sub.6H.sub.6CH.sub.2O—, or a glycoside; R.sub.4 is —H, —OH, CH.sub.3O—, CH.sub.3CH.sub.2O—, (CH.sub.3).sub.3CO—, C.sub.6H.sub.6CH.sub.2O—, or a glycoside; R.sub.5 is —H, —OH, CH.sub.3O—, CH.sub.3CH.sub.2O—, (CH.sub.3).sub.3CO—, C.sub.6H.sub.6CH.sub.2O—, or a glycoside; R.sub.6 is —H, —OH, CH.sub.3O—, CH.sub.3CH.sub.2O—, (CH.sub.3).sub.3CO—, C.sub.6H.sub.6CH.sub.2O—, or a glycoside.

3. The method for preparing the diselenide compound according to claim 1, wherein the polar solvent is water, methanol or ethanol.

4. The method for preparing the diselenide compound according to claim 1, wherein the dihydroflavonol compound comprises racemates, 2S,3S isomers, and 2R,3R isomers of the dihydroflavonol compound.

5. The method for preparing the diselenide compound according to claim 1, wherein the diselenide compound is obtained by naturally cooling to room temperature after the reaction is completed, adjusting the pH value of the reaction solution to 3˜6.5, extracting, separating by column chromatography, and lyophilizing.

Description

BREIF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a 1H nuclear magnetic resonance (NMR) spectrum of the product in Example 1 of the present disclosure;

(2) FIG. 2 is a 13C nuclear magnetic resonance (NMR) spectrum of the product in Example 1 of the present disclosure;

(3) FIG. 3 is a mass spectrum of the product in Example 1 of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

(4) In order to make the technical means, creative features, achieved purpose and efficacy realized by the present disclosure easy to understand, the method of preparing diselenide compound of the present disclosure is specified below in conjunction with the embodiments.

EXAMPLE 1

(5) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(6) ##STR00005##

(7) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 80° C., and kept for 45 minutes. 2.81 g of sodium hydroxide was added, and reacted for 10 minutes under the temperature being controlled at 80° C., and 7.80 g of selenium dioxide was added and reacted for 70 minutes under the temperature being controlled at 80° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 3˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 8.63%.

EXAMPLE 2

(8) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(9) ##STR00006##

(10) 15 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 90° C., and kept for 45 minutes. 0.75 g of sodium hydroxide was added, and reacted for 60 minutes under the temperature being controlled at 90° C., and 4.16 g of selenium dioxide was added and reacted for 70 minutes under the temperature being controlled at 90° C., and then the reaction was completed. Then, the heating was turned off, the pH was adjusted to 3-6.5 with hydrochloric acid after naturally cooling to room temperature after, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 10.26%.

EXAMPLE 3

(11) In this embodiment, dihydromyricetin is selected as the dihydroflavonol compound, which has the following general formula:

(12) ##STR00007##

(13) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 100° C., and kept for 45 minutes. 2.53 g of sodium hydroxide was added and reacted for 40 minutes under the temperature being controlled at 100° C., and 9.36 g of selenium dioxide was added and reacted for 30 minutes under the temperature being controlled at 100° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 3˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 9.86%.

EXAMPLE 4

(14) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(15) ##STR00008##

(16) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 90° C., and kept for 40 minutes. 1.69 g of sodium hydroxide was added and reacted for 20 minutes under the temperature being controlled at 90° C., and 6.24 g of selenium dioxide was added and reacted for 60 minutes under the temperature being controlled at 90° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 3˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 20.2%.

EXAMPLE 5

(17) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(18) ##STR00009##

(19) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 90° C., and kept for 50 minutes. 2.36 g of sodium hydroxide was added and reacted for 50 minutes under the temperature being controlled at 90° C., and 6.24 g of selenium dioxide was added and reacted for 80 minutes under the temperature being controlled at 90° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 3˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 21.75%.

EXAMPLE 6

(20) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(21) ##STR00010##

(22) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 95° C., and kept for 45 minutes. 4.05 g of sodium tert-butoxide was added and reacted for 20 minutes under the temperature being controlled at 95° C., and 4.69 g of selenium dioxide was added and reacted for 70 minutes under the temperature being controlled at 95° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 3˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 13%

EXAMPLE 7

(23) In this embodiment, dihydromyricetin was selected as the dihydroflavonol compound, which has the following general formula:

(24) ##STR00011##

(25) 22.5 g of dihydromyricetin was added into a four-necked flask (specification 500 mL), 200 mL of water was added, heated to 90° C., and kept for 45 minutes. 4.05 g of sodium tert-butoxide was added and reacted for 5 minutes under the temperature being controlled at 90° C., and 6.24 g of selenium dioxide was added and reacted for 150 minutes under the temperature being controlled at 90° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 6˜6.5 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dimyricetin-based diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 38%.

(26) The products obtained in the above seven embodiments were analyzed by NMR and mass (MS) spectrometry, respectively. All of them were verified to be dimyricetin-based diselenide. Only the MS spectrum, 1H NMR spectrum and 13C spectrum measured in Example 1 are listed below.

(27) According to the 1H NMR spectrum shown in FIG. 1, the 1H NMR spectrum data of the product are as follows:

(28) 1H NMR (400 MHZ, DMSO-d6): δ 12.73(s,1H), 10.7(s,1H) 9.15(s,1H), 8.93 (S,2H), 8.68(s, 1H), 7.26 (S,2H), 6.08(s,1H).

(29) According to the 13C NMR spectrum shown in FIG. 2, the data of the 13C NMR spectrum of the product is as follows:

(30) 13C NMR (400 MHZ, DMSO-d6): δ 175.95, 166.25, 162.39, 156.95, 147.55, 145.87, 145.87, 136.30, 136.30, 121.63, 107.97, 107.97, 103.67, 98.14, 95.00.

(31) According to the MS spectrum shown in FIG. 3, the highest molecular ion peak is 790.887, and selenium has multiple isotope peaks.

(32) From the information provided by the 1H NMR spectrum, 13C NMR spectrum and MS spectrum, it can be seen that the product obtained is dimyricetin-based diselenide.

EXAMPLE 8

(33) In this embodiment, dihydroflavonol was selected as the dihydroflavonol compound, which has the following general formula:

(34) ##STR00012##

(35) 22.5 g of dihydroflavonol was added into a four-necked flask (specification 500 mL), 200 mL of 30% methanol was added, heated to 90° C., and kept for 45 minutes. 3.62 g of sodium hydroxide was added and reacted for 40 minutes under the temperature being controlled at 90° C., and 9.24 g of selenium dioxide was added and reacted for 70 minutes under the temperature being controlled at 90° C., and then the reaction was complete. Then, the heating was turned off, the pH was adjusted to 5˜6 with hydrochloric acid after naturally cooling to room temperature, and methanol was used for extraction. Dihydroflavonol diselenide product was obtained by lyophilizing after column chromatography separation, the yield was 12.6%.

(36) The resulting products were analyzed by NMR and mass spectrometry, respectively, and the analysis confirmed that the product is dihydroflavonol diselenide.

(37) The method for preparing diselenide compound related to the present disclosure is not limited to the scope of specific embodiments. The above content is only a basic description of the present disclosure, and any equivalent transformations made based on the technical solutions of the present disclosure shall fall within the scope of protection of the present disclosure.