Preparation method of guineensine

Abstract

A synthesis method of guineensine includes steps of: 1) performing a nucleophilic reaction on a compound A with 1-phenyl-5-thiol-1H-1,2,3,4-tetrazole under alkaline conditions to obtain a compound B;2) oxidizing the compound B with ammonium tungstate and hydrogen peroxide to give compound C; 3) oxidizing a compound D to obtain a compound E; 4) mixing and stirring the compound C and compound E under alkaline condition at -78 DEG C to obtain a compound F; 5) in the presence of n-butyllithium, adding ethyl chloroformate to the compound F to obtain a compound G at -78 DEG C; 6) refluxing the compound G with triphenylphosphine and phenol in a toluene solvent to prepare a compound H; 7) performing ester group hydrolysis on the compound H with NaOH in a mixed solvent of ethanol / water to preparea compound I; 8) condensing the compound I with isobutylamine to obtain the guineensine J. The structure formulas of the compound A, B, C ... J are represented as the specification. The guineensine can overcome the defects of a natural extract, ganoderiol, and is suitable for pharmaceutical preparation technology.

Description

technical field

[0001] The invention relates to the field of drug synthesis, in particular to a preparation method of guinea piperine. Background technique

[0002] Guineensine is an active natural product that exists in the Piperaceae family. Studies have shown that Guinea piperine has good anti-cardiovascular and cerebrovascular effects. It has been reported in the literature that guinea piperine can be extracted from the traditional Chinese medicine Smilax smilax. However, the content of guinea piperine extracted from natural products cannot meet the demand for medicine, and there are unfavorable factors such as unstable plant planting yield and high extraction cost. Therefore, obtaining guinea piperine by chemical synthesis in a relatively economical method has a great practical demand. Contents of the invention

[0003] In view of this, it is necessary to seek a preparation method of guinea piperine to make up for the deficiency of guinea piperine, thereby satisfyi...

Examples

preparation example Construction

[0009] Such as figure 1 Shown, the preparation method of guinea piperine, comprises the steps:

[0010]

[0011] Compound A (1.0 equiv) was dissolved in acetone, 1-phenyl-1H-tetrazol-5-thiol (1.0 equiv) was added, followed by potassium carbonate (1.5 equiv). The reaction system was heated to reflux and reacted overnight. After the reaction, the reaction system was concentrated, acetone was removed, ethyl acetate was added to redissolve, filtered, potassium carbonate was removed, the organic phase was washed twice with water, the organic phase was dried, and concentrated to obtain the crude product B. The crude product B can be directly put into the next reaction.

[0012]

[0013] Compound B (1.0 equivalent) was dissolved in ethanol, ammonium heptamolybdatetetrahydrate (0.2 equivalent) was added, and the temperature of the reaction system dropped to 0°C. The same volume of hydrogen peroxide as ethanol was then added, and the reaction was stirred for 18 hours. After t...

Embodiment

[0027] The following is the specific example part, wherein, the proton nuclear magnetic resonance spectrum and the carbon nuclear magnetic resonance spectrum of the following compounds are all obtained by the method of nuclear magnetic resonance, and the instrument and test conditions used in the test are as follows: Brüker Advance 300 ( 1 H: 300MHz, 13 C: 75MHz), Brüker Advance 400 ( 1 H: 400MHz, 13 C: 100MHz), Brüker Advance 500 ( 1 H: 500MHz, 13 C: 125MHz), using TMS or the residual non-deuterated solvent in the deuterated solvent as internal standard. The preparation method of the Guinea piperine of the present embodiment is as follows:

[0028]

[0029] Compound A (50.8 g) was dissolved in acetone (700 mL), 1-phenyl-1H-tetrazol-5-thiol (53.9 g) was added, followed by potassium carbonate (62.7 g). The reaction system was heated to reflux and reacted overnight. After the reaction was finished, the reaction system was concentrated, acetone was removed, ethyl acetate...

technical field

[0001] The invention relates to the field of drug synthesis, in particular to a preparation method of guinea piperine. Background technique

[0002] Guineensine is an active natural product that exists in the Piperaceae family. Studies have shown that Guinea piperine has good anti-cardiovascular and cerebrovascular effects. It has been reported in the literature that guinea piperine can be extracted from the traditional Chinese medicine Smilax smilax. However, the content of guinea piperine extracted from natural products cannot meet the demand for medicine, and there are unfavorable factors such as unstable plant planting yield and high extraction cost. Therefore, obtaining guinea piperine by chemical synthesis in a relatively economical method has a great practical demand. Contents of the invention

[0003] In view of this, it is necessary to seek a preparation method of guinea piperine to make up for the deficiency of guinea piperine, thereby satisfyi...

Examples

preparation example Construction

[0009] Such as figure 1 Shown, the preparation method of guinea piperine, comprises the steps:

[0010]

[0011] Compound A (1.0 equiv) was dissolved in acetone, 1-phenyl-1H-tetrazol-5-thiol (1.0 equiv) was added, followed by potassium carbonate (1.5 equiv). The reaction system was heated to reflux and reacted overnight. After the reaction, the reaction system was concentrated, acetone was removed, ethyl acetate was added to redissolve, filtered, potassium carbonate was removed, the organic phase was washed twice with water, the organic phase was dried, and concentrated to obtain the crude product B. The crude product B can be directly put into the next reaction.

[0012]

[0013] Compound B (1.0 equivalent) was dissolved in ethanol, ammonium heptamolybdatetetrahydrate (0.2 equivalent) was added, and the temperature of the reaction system dropped to 0°C. The same volume of hydrogen peroxide as ethanol was then added, and the reaction was stirred for 18 hours. After t...

Embodiment

[0027] The following is the specific example part, wherein, the proton nuclear magnetic resonance spectrum and the carbon nuclear magnetic resonance spectrum of the following compounds are all obtained by the method of nuclear magnetic resonance, and the instrument and test conditions used in the test are as follows: Brüker Advance 300 ( 1 H: 300MHz, 13 C: 75MHz), Brüker Advance 400 ( 1 H: 400MHz, 13 C: 100MHz), Brüker Advance 500 ( 1 H: 500MHz, 13 C: 125MHz), using TMS or the residual non-deuterated solvent in the deuterated solvent as internal standard. The preparation method of the Guinea piperine of the present embodiment is as follows:

[0028]

[0029] Compound A (50.8 g) was dissolved in acetone (700 mL), 1-phenyl-1H-tetrazol-5-thiol (53.9 g) was added, followed by potassium carbonate (62.7 g). The reaction system was heated to reflux and reacted overnight. After the reaction was finished, the reaction system was concentrated, acetone was removed, ethyl acetate...

Images