The preparation method of antrodia

Abstract

The invention discloses an antrocin preparation method. Carnosic acid is taken as a raw material, and an ozone oxidation cleavage reaction, a Birch reduction reaction, an ester condensation reaction and an iodine substitution-elimination reaction are carried out, so that a molecular skeleton structure is constructed rapidly, thus asymmetrical total synthesis of the antrocin is completed. The antrocin preparation method can be used to synthesize large amounts of antrocin, and the synthesized antrocin can be used to research pathology, toxicology and structure-activity relationships, in addition, biological activity of the antrocin can be clarified and improved by structure modification.

Description

technical field

[0001] The invention relates to a preparation method of antrodiadin. Background technique

[0002] Antrocin (Antrocin) was obtained from Taiwan, China in 1994 by Professor Hung-Chen Chiang and his collaborators. Antrodiacamphorata), the molecular structure is

[0003] The active ingredient triterpenoids of Antrodia Cinnamomea are also found in other fungi of the genus Lepidobacterium except for some special ones. However, the sesquiterpene compound Antrodia can only be isolated from the fruiting body of Antrodia camphorata, and it has not been reported that Antrodia camphorata obtained from artificially cultivated Antrodia camphorata.

[0004] Structurally, antrodiacin is a sesquiterpene lactone with a 6.6.5 tricyclic structure, including three chiral centers and two all-carbon substitution centers. In 2011, Professor Zeng Yaoming of Chaoyang University of Science and Technology in Taiwan conducted research on the biological activity of antrodia. Studie...

Examples

preparation example Construction

[0031] In the preparation method of antrocardine of the present invention, each step of the reaction is carried out under the protection of nitrogen, in a dry solvent, and under the condition of anhydrous.

[0032] In the preparation method of antrocharin of the present invention, all the chemical reagents used are commercially available raw materials without further treatment.

[0033] Such as figure 1 The preparation method of the antrocardin of one embodiment shown, comprises the steps:

[0034] S10. Dissolving carnosic acid in the first organic solvent, then cooling to -78° C., blowing air into ozone, and obtaining the first reaction liquid after sufficient reaction.

[0035] The structural formula of carnosic acid is

[0036] In S10, the first organic solvent may be dichloromethane, methanol or a mixed liquid of dichloromethane and methanol with a volume ratio of 2-6:1.

[0037] In S10, the operation time of air blowing into ozone is 1 hour.

[0038] Preferably, the...

Embodiment 1

[0083] Under anhydrous conditions, the structural formula is Carnosic acid (carnosic acid, 25.0g, 75.3mmol) was dissolved in a 3:1 mixed solvent of dichloromethane and methanol (400mL), then cooled to -78°C, ozone was introduced, and the first gas was obtained after bubbling for 1 hour. a reaction solution.

[0084] Sodium borohydride (12.6g, 450.0mmol) was added to the first reaction solution, and after vigorous stirring for 1 hour, a saturated ammonium chloride solution was added to quench the reaction, extracted with ethyl acetate (3×400mL), and the organic phase was washed with saturated Washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purify with silica gel column chromatography then, obtain 11.5g structural formula is Compound A, yield 58%. The detection data of compound A are as follows:

[0085] (c=0.1, CHCl 3 ); IR (thin film, ν cm -1 ):2956,2917,1768,1447,1345,1216,1023,767; 1 H NMR (400MHz, CDC...

Embodiment 2

[0092] Under anhydrous conditions, the structural formula is Carnosic acid (carnosic acid, 25.0g, 75.3mmol) was dissolved in a 3:1 mixed solvent of dichloromethane and methanol (400mL), then cooled to -78°C, ozone was introduced, and the first gas was obtained after bubbling for 1 hour. a reaction solution.

[0093] Sodium borohydride (12.6g, 450.0mmol) was added to the first reaction solution, and after vigorous stirring for 1 hour, a saturated ammonium chloride solution was added to quench the reaction, extracted with ethyl acetate (3×400mL), and the organic phase was washed with saturated Washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purify with silica gel column chromatography then, obtain 11.5g structural formula is Compound A, yield 56%. The detection data of compound A are as follows: (c=0.1, CHCl 3 ); IR(thinfilm,νcm -1 ):2956,2920,1765,1443,1341,1209,1023,767; 1 H NMR (400MHz, CDCl 3 )δ10.19(s...

technical field

[0001] The invention relates to a preparation method of antrodiadin. Background technique

[0002] Antrocin (Antrocin) was obtained from Taiwan, China in 1994 by Professor Hung-Chen Chiang and his collaborators. Antrodiacamphorata), the molecular structure is

[0003] The active ingredient triterpenoids of Antrodia Cinnamomea are also found in other fungi of the genus Lepidobacterium except for some special ones. However, the sesquiterpene compound Antrodia can only be isolated from the fruiting body of Antrodia camphorata, and it has not been reported that Antrodia camphorata obtained from artificially cultivated Antrodia camphorata.

[0004] Structurally, antrodiacin is a sesquiterpene lactone with a 6.6.5 tricyclic structure, including three chiral centers and two all-carbon substitution centers. In 2011, Professor Zeng Yaoming of Chaoyang University of Science and Technology in Taiwan conducted research on the biological activity of antrodia. Studie...

Examples

preparation example Construction

[0031] In the preparation method of antrocardine of the present invention, each step of the reaction is carried out under the protection of nitrogen, in a dry solvent, and under the condition of anhydrous.

[0032] In the preparation method of antrocharin of the present invention, all the chemical reagents used are commercially available raw materials without further treatment.

[0033] Such as figure 1 The preparation method of the antrocardin of one embodiment shown, comprises the steps:

[0034] S10. Dissolving carnosic acid in the first organic solvent, then cooling to -78° C., blowing air into ozone, and obtaining the first reaction liquid after sufficient reaction.

[0035] The structural formula of carnosic acid is

[0036] In S10, the first organic solvent may be dichloromethane, methanol or a mixed liquid of dichloromethane and methanol with a volume ratio of 2-6:1.

[0037] In S10, the operation time of air blowing into ozone is 1 hour.

[0038] Preferably, the...

Embodiment 1

[0083] Under anhydrous conditions, the structural formula is Carnosic acid (carnosic acid, 25.0g, 75.3mmol) was dissolved in a 3:1 mixed solvent of dichloromethane and methanol (400mL), then cooled to -78°C, ozone was introduced, and the first gas was obtained after bubbling for 1 hour. a reaction solution.

[0084] Sodium borohydride (12.6g, 450.0mmol) was added to the first reaction solution, and after vigorous stirring for 1 hour, a saturated ammonium chloride solution was added to quench the reaction, extracted with ethyl acetate (3×400mL), and the organic phase was washed with saturated Washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purify with silica gel column chromatography then, obtain 11.5g structural formula is Compound A, yield 58%. The detection data of compound A are as follows:

[0085] (c=0.1, CHCl 3 ); IR (thin film, ν cm -1 ):2956,2917,1768,1447,1345,1216,1023,767; 1 H NMR (400MHz, CDC...

Embodiment 2

[0092] Under anhydrous conditions, the structural formula is Carnosic acid (carnosic acid, 25.0g, 75.3mmol) was dissolved in a 3:1 mixed solvent of dichloromethane and methanol (400mL), then cooled to -78°C, ozone was introduced, and the first gas was obtained after bubbling for 1 hour. a reaction solution.

[0093] Sodium borohydride (12.6g, 450.0mmol) was added to the first reaction solution, and after vigorous stirring for 1 hour, a saturated ammonium chloride solution was added to quench the reaction, extracted with ethyl acetate (3×400mL), and the organic phase was washed with saturated Washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purify with silica gel column chromatography then, obtain 11.5g structural formula is Compound A, yield 56%. The detection data of compound A are as follows: (c=0.1, CHCl 3 ); IR(thinfilm,νcm -1 ):2956,2920,1765,1443,1341,1209,1023,767; 1 H NMR (400MHz, CDCl 3 )δ10.19(s...

Images