Method for synthesizing macrocyclic polydithioether compound gymnorrhizol

Abstract

The invention relates to a method for synthesizing novel macrocyclic polydisulfide gymnorrhizol with an active constitutional formula as follows for resisting II-type diabetes. The method comprises: 3, 3'- disulfide group di (2- hydroxy propyl-1- thiosulfate) reacts with 2-hydroxide radical-1, 3- thioglycerin dibasic salt to obtain the gymnorrhizol, or the 3, 3'- disulfide group di (2- hydroxy propyl-1- thiosulfate) reacts with 2-hydroxide radical-1, 3-trimethylene thiosulfate to obtain the gymnorrhizol. The synthetic method of the gymnorrhizol provided by the invention has a new synthetic route, simple operation; compared with the prior art, the method has high yield and good reproduction quality.

Description

technical field

[0001] The invention relates to a synthesis method of a novel macrocyclic polydisulfide compound gymnorrhizol with anti-type II diabetes activity. Background technique

[0002] Hexathiol is a fifteen-membered ring polydisulfide compound (Tetrahedron Letters, Vol.45, No.28, 2004, 5533) with a new skeleton structure isolated from marine organisms. Its structural formula As follows:

[0003]

[0004] Formula 1

[0005] Studies have shown that this compound has good inhibitory activity on the type II diabetes target PTP1B, and its inhibitory concentration is IC50=14.9 μM. In addition, according to literature reports, cyclic thioether compounds can also be used as phase transfer catalysts and complexing agents for metal ions. Therefore, the macrocyclic polydisulfide compound hexathiol has a good application prospect. The previous synthesis method of this compound was obtained by oxidizing 1,3-dimercapto-2-propanol (CN200510025808.6). Althou...

Examples

Embodiment 1

[0054] Example 1: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0055] Add 3 grams of sodium borohydride and 7.7 grams of sulfur powder into a three-necked flask with nitrogen gas, reflux condenser and drying tube, cool in an ice bath to below 5°C, and slowly add 40 milliliters of anhydrous tetrahydrofuran dropwise, and the material gradually turns red. , and gas was released, the ice bath was removed after the addition, and the stirring was continued for 30 minutes, and a yellow solid was formed. Slowly add 3.7 g of epichlorohydrin dissolved in 10 ml of anhydrous tetrahydrofuran dropwise to the above reactant, and stir at room temperature for 5 hours; add water to decompose excess sodium trithioborohydride, separate the organic layer, and use diethyl ether for the aqueous phase Extract, combine the extracts, dry over anhydrous magnesium sulfate, filter and evaporate the solvent under reduced pressure, use petroleum ether: acetone (volume ratio 5:1) as the eluent, and ob...

Embodiment 2

[0057] Example 2: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0058] Mix 8.2 grams of sodium sulfide nonahydrate and 1.1 grams of sulfur powder, add 40 milliliters of 95% ethanol and heat to reflux, add 4 grams of 1-bromo-3-chloro-2-propanol after 30 minutes, continue to heat and reflux for 3 hours, evaporate under reduced pressure The solvent was removed, the residue was extracted with diethyl ether, the organic phase was dried with sodium sulfate, filtered, and concentrated to obtain a red oil, using petroleum ether: acetone (volume ratio 5:1) as the eluent, the white powder 4.8 was obtained by silica gel column chromatography gram, yield 85%. Since bromine is more reactive than chlorine, a chlorine-only product is obtained.

Embodiment 3

[0059] Example 3: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0060] Dissolve 2.16 g of 1-bromo-3-chloroisopropanol in 15 ml of 50% ethanol, add 3.1 g of sodium thiosulfate pentahydrate, heat to reflux for 2 hours, add 3.2 g of solid iodine while hot, and continue heating to reflux for 1 hour After cooling down, the reactant was extracted with ethyl acetate, and the combined organic phases were washed successively with sodium bicarbonate solution, sodium thiosulfate solution, saturated brine, dried over magnesium sulfate, concentrated by filtration, and the residue was prepared with petroleum ether: acetone (volume ratio 5:1) was used as the eluent, and 1 g of white solid was obtained by silica gel column chromatography with a yield of 65%.

technical field

[0001] The invention relates to a synthesis method of a novel macrocyclic polydisulfide compound gymnorrhizol with anti-type II diabetes activity. Background technique

[0002] Hexathiol is a fifteen-membered ring polydisulfide compound (Tetrahedron Letters, Vol.45, No.28, 2004, 5533) with a new skeleton structure isolated from marine organisms. Its structural formula As follows:

[0003]

[0004] Formula 1

[0005] Studies have shown that this compound has good inhibitory activity on the type II diabetes target PTP1B, and its inhibitory concentration is IC50=14.9 μM. In addition, according to literature reports, cyclic thioether compounds can also be used as phase transfer catalysts and complexing agents for metal ions. Therefore, the macrocyclic polydisulfide compound hexathiol has a good application prospect. The previous synthesis method of this compound was obtained by oxidizing 1,3-dimercapto-2-propanol (CN200510025808.6). Althou...

Examples

Embodiment 1

[0054] Example 1: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0055] Add 3 grams of sodium borohydride and 7.7 grams of sulfur powder into a three-necked flask with nitrogen gas, reflux condenser and drying tube, cool in an ice bath to below 5°C, and slowly add 40 milliliters of anhydrous tetrahydrofuran dropwise, and the material gradually turns red. , and gas was released, the ice bath was removed after the addition, and the stirring was continued for 30 minutes, and a yellow solid was formed. Slowly add 3.7 g of epichlorohydrin dissolved in 10 ml of anhydrous tetrahydrofuran dropwise to the above reactant, and stir at room temperature for 5 hours; add water to decompose excess sodium trithioborohydride, separate the organic layer, and use diethyl ether for the aqueous phase Extract, combine the extracts, dry over anhydrous magnesium sulfate, filter and evaporate the solvent under reduced pressure, use petroleum ether: acetone (volume ratio 5:1) as the eluent, and ob...

Embodiment 2

[0057] Example 2: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0058] Mix 8.2 grams of sodium sulfide nonahydrate and 1.1 grams of sulfur powder, add 40 milliliters of 95% ethanol and heat to reflux, add 4 grams of 1-bromo-3-chloro-2-propanol after 30 minutes, continue to heat and reflux for 3 hours, evaporate under reduced pressure The solvent was removed, the residue was extracted with diethyl ether, the organic phase was dried with sodium sulfate, filtered, and concentrated to obtain a red oil, using petroleum ether: acetone (volume ratio 5:1) as the eluent, the white powder 4.8 was obtained by silica gel column chromatography gram, yield 85%. Since bromine is more reactive than chlorine, a chlorine-only product is obtained.

Embodiment 3

[0059] Example 3: Synthesis of 3,3'-dithiobis(1-chloro-2-propanol):

[0060] Dissolve 2.16 g of 1-bromo-3-chloroisopropanol in 15 ml of 50% ethanol, add 3.1 g of sodium thiosulfate pentahydrate, heat to reflux for 2 hours, add 3.2 g of solid iodine while hot, and continue heating to reflux for 1 hour After cooling down, the reactant was extracted with ethyl acetate, and the combined organic phases were washed successively with sodium bicarbonate solution, sodium thiosulfate solution, saturated brine, dried over magnesium sulfate, concentrated by filtration, and the residue was prepared with petroleum ether: acetone (volume ratio 5:1) was used as the eluent, and 1 g of white solid was obtained by silica gel column chromatography with a yield of 65%.

Images