Application of isoalantolactone derivative and salt thereof in preparation of medicines for treating lung fibration

Abstract

The invention relates to an application of an isoalantolactone derivative and a salt thereof in the preparation of medicines for treating lung fibration, and provides an isoalantolactone derivative represented by formula (I). An acid for forming the salt is an inorganic acid or an organic acid, the inorganic acid is selected from hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, boric acid, seleninic acid, phosphomolybdic acid, phosphorous acid and sulfurous acid, and the organic acid is selected from citric acid, maleic acid, D-malic acid, L-malic acid, DL-malic acid, L-lactic acid, D-lactic acid, DL-lactic acid, oxalic acid, methanesulfonic acid, pentanoic acid, oleic acid, lauric acid, p-methyl benzenesulfonic acid, 1-naphthalenesulfonic acid, 2-naphthalenesulfonic acid, phthalic acid, tartaric acid, propane diacid, succinic acid, fumaric acid, glycollic acid, thioglycollic acid, glycine, sarcosine, sulfonic acid, nicotinic acid, methylpyridine acid, isonicotinic acid, benzoic acid and substituted benzoic acid.

Description

[0001] Technical field:

[0002] The present invention relates to inulin derivatives and their salts and their application and preparation.

[0003] Background technique:

[0004] Inula helenium is a plant of the genus Inula in the family Compositae, a perennial herb whose roots are used for medicinal purposes. It has the functions of invigorating the spleen and harmonizing the stomach, regulating qi and relieving depression, relieving pain and preventing miscarriage. It is used for chest and flank, abdominal distension and pain, vomiting and diarrhea, chest and flank contusion, pain in the chest and flank, restless fetal movement and other diseases. The volatile oil of inulin contains iso-inuricolide, iso-inuricolide and other components. Its chemical structure is similar to that of Sandonian, and it has anthelmintic effect on pigs, dogs, and cats. Its curative effect is better than that of Sandonian, and its toxicity is lower. Low.

[0005] Isoacarina lactone (CAS: 470-17-7...

Examples

Embodiment 1

[0028] Preparation of compound (II)

[0029]

[0030] 1) Preparation of Compound (1.1)

[0031]

[0032] 1) Isoaurinolide (1.0g, 4.3mmol) was dissolved in dichloromethane (16mL), and peroxybenzoic acid (1.1g, 5.2mmol) was slowly added to the system in batches, reacted at room temperature for 3 hours, saturated The reaction was quenched with sodium thiosulfate (16 mL), extracted with dichloromethane (16 mL×3), the organic phase was washed with saturated aqueous sodium bicarbonate (16 mL), dried and concentrated, and purified by column chromatography (petroleum ether: ethyl acetate=20: 1) Obtain compound 1.2 (white solid, 984 mg, yield 92.0%).

[0033] 2) preparation of compound (I-II),

[0034]

[0035] The compound 1.2 obtained in step 1) was dissolved in dichloromethane (98mL), potassium carbonate (16.4g, 118.9mmol) and dimethylamine hydrochloride (4.8g, 59.4mmol) were added to the system in turn, and the mixed system was stirred Reflux reaction for 3 hours, after...

Embodiment 2

[0041] Preparation of compound (III)

[0042]

[0043] 1) Preparation of compound 1.3

[0044]

[0045] At 0°C, dissolve selenium dioxide (87.5mg, 0.75mmol) in dichloromethane (5mL), add tert-butanol peroxide (0.37mL), and stir for 30 minutes. , 2.15mmol) of dichloromethane (5mL) solution was slowly added to the above system, stirred at room temperature for 24 hours, quenched with saturated aqueous sodium thiosulfate (8mL), extracted with dichloromethane (8mL×3), dried Concentrate and purify by column chromatography (petroleum ether: ethyl acetate = 9:1 to 3:1) to obtain compound 1.23 (white solid, 350 mg, yield: 82.8%).

[0046] 2) Preparation of compound (I-III)

[0047]

[0048] The compound 1.3 obtained in the previous step was dissolved in dichloromethane (35mL), potassium carbonate (5.8g, 42.2mmol) and dimethylamine hydrochloride (1.7g, 21.1mmol) were added to the system successively, and the mixed system was stirred and refluxed Reacted for 3 hours. After th...

Embodiment 3

[0053] Preparation of Compound IV

[0054]

[0055] 1) Preparation of compound 1.4

[0056]

[0057] Compound 1.3 (112mg, 0.45mmol) was dissolved in dichloromethane (1mL), and a solution of peroxybenzoic acid (100mg, 0.60mmol) in dichloromethane (1mL) was slowly added dropwise to the above system, and reacted at room temperature for 2 hours , quenched the reaction with saturated sodium thiosulfate (2 mL), extracted with dichloromethane (2 mL×3), dried and concentrated, and purified by column chromatography (petroleum ether: ethyl acetate = 4:1 to 1:1) to obtain compound 1.4 ( White solid, 89 mg, yield: 74.5%).

[0058] 2) Preparation of compound (I-IV)

[0059]

[0060] The compound 1.4 obtained in the previous step was dissolved in dichloromethane (35mL), potassium carbonate (5.8g, 42.2mmol) and dimethylamine hydrochloride (1.7g, 21.1mmol) were added to the system successively, and the mixed system was stirred and refluxed Reacted for 3 hours. After the reaction, ...

[0001] Technical field:

[0002] The present invention relates to inulin derivatives and their salts and their application and preparation.

[0003] Background technique:

[0004] Inula helenium is a plant of the genus Inula in the family Compositae, a perennial herb whose roots are used for medicinal purposes. It has the functions of invigorating the spleen and harmonizing the stomach, regulating qi and relieving depression, relieving pain and preventing miscarriage. It is used for chest and flank, abdominal distension and pain, vomiting and diarrhea, chest and flank contusion, pain in the chest and flank, restless fetal movement and other diseases. The volatile oil of inulin contains iso-inuricolide, iso-inuricolide and other components. Its chemical structure is similar to that of Sandonian, and it has anthelmintic effect on pigs, dogs, and cats. Its curative effect is better than that of Sandonian, and its toxicity is lower. Low.

[0005] Isoacarina lactone (CAS: 470-17-7...

Examples

Embodiment 1

[0028] Preparation of compound (II)

[0029]

[0030] 1) Preparation of Compound (1.1)

[0031]

[0032] 1) Isoaurinolide (1.0g, 4.3mmol) was dissolved in dichloromethane (16mL), and peroxybenzoic acid (1.1g, 5.2mmol) was slowly added to the system in batches, reacted at room temperature for 3 hours, saturated The reaction was quenched with sodium thiosulfate (16 mL), extracted with dichloromethane (16 mL×3), the organic phase was washed with saturated aqueous sodium bicarbonate (16 mL), dried and concentrated, and purified by column chromatography (petroleum ether: ethyl acetate=20: 1) Obtain compound 1.2 (white solid, 984 mg, yield 92.0%).

[0033] 2) preparation of compound (I-II),

[0034]

[0035] The compound 1.2 obtained in step 1) was dissolved in dichloromethane (98mL), potassium carbonate (16.4g, 118.9mmol) and dimethylamine hydrochloride (4.8g, 59.4mmol) were added to the system in turn, and the mixed system was stirred Reflux reaction for 3 hours, after...

Embodiment 2

[0041] Preparation of compound (III)

[0042]

[0043] 1) Preparation of compound 1.3

[0044]

[0045] At 0°C, dissolve selenium dioxide (87.5mg, 0.75mmol) in dichloromethane (5mL), add tert-butanol peroxide (0.37mL), and stir for 30 minutes. , 2.15mmol) of dichloromethane (5mL) solution was slowly added to the above system, stirred at room temperature for 24 hours, quenched with saturated aqueous sodium thiosulfate (8mL), extracted with dichloromethane (8mL×3), dried Concentrate and purify by column chromatography (petroleum ether: ethyl acetate = 9:1 to 3:1) to obtain compound 1.23 (white solid, 350 mg, yield: 82.8%).

[0046] 2) Preparation of compound (I-III)

[0047]

[0048] The compound 1.3 obtained in the previous step was dissolved in dichloromethane (35mL), potassium carbonate (5.8g, 42.2mmol) and dimethylamine hydrochloride (1.7g, 21.1mmol) were added to the system successively, and the mixed system was stirred and refluxed Reacted for 3 hours. After th...

Embodiment 3

[0053] Preparation of Compound IV

[0054]

[0055] 1) Preparation of compound 1.4

[0056]

[0057] Compound 1.3 (112mg, 0.45mmol) was dissolved in dichloromethane (1mL), and a solution of peroxybenzoic acid (100mg, 0.60mmol) in dichloromethane (1mL) was slowly added dropwise to the above system, and reacted at room temperature for 2 hours , quenched the reaction with saturated sodium thiosulfate (2 mL), extracted with dichloromethane (2 mL×3), dried and concentrated, and purified by column chromatography (petroleum ether: ethyl acetate = 4:1 to 1:1) to obtain compound 1.4 ( White solid, 89 mg, yield: 74.5%).

[0058] 2) Preparation of compound (I-IV)

[0059]

[0060] The compound 1.4 obtained in the previous step was dissolved in dichloromethane (35mL), potassium carbonate (5.8g, 42.2mmol) and dimethylamine hydrochloride (1.7g, 21.1mmol) were added to the system successively, and the mixed system was stirred and refluxed Reacted for 3 hours. After the reaction, ...

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