Method for synthesizing artepillin C and intermediate compound thereof
The present invention relates to a method for synthesizing artepillin C and a synthetic method for synthesizing an intermediate compound for use in preparing artepillin C. The structural formula of artepillin C is shown in the following formula (IV), and the intermediate compound is shown in the following formula (II). The synthesis method includes the following steps: a first reaction step: in the presence of a base initiator, a compound A shown in formula I and 3,3-dimethylallyl bromide are mixed, the reaction continues for a first reaction time and is stopped to generate an intermediate of artepillin C shown in formula II; and a second reaction step: the intermediate of artepillin C is dissolved in an aqueous alcohol solution and then mixed with an alkali metal salt, and the reaction continues for a second reaction time to generate artepillin C.
1. A method for synthesizing artepillin C, which comprises the following steps:
a first reaction step: in the presence of a base initiator, a compound A shown in formula I and 3,3-dimethylallyl bromide are mixed in a solvent including at least one selected from toluene, dimethylformamide, tetrahydrofuran, and dimethylsulfoxide to lead a first reaction in an ice bath continuously for 72 hrs, and then water is poured into the reaction solution to stop the reaction to generate a first reaction product, which comprises an intermediate of artepillin C shown in formula II,
in which R is C 1-6 alkyl, and
a second reaction step: the intermediate of artepillin C is dissolved in an aqueous alcohol solution and then mixed with an alkali metal salt, and the reaction continues for a second reaction time to generate a second reaction product, which comprises artepillin C shown in formula IV;
wherein
in the first reaction step, the molar ratio of the compound A to 3,3-dimethylallyl bromide is 1:2, the molar ratio of the compound A to the base initiator is 1:2, and the first reaction is carried out in a vacuum environment with argon; and
in the second reaction step, the second reaction time is in the range of 8 h to 20 h.
2. The method for synthesizing artepillin C of claim 1 , wherein the base initiator is sodium hydride.
3. The method for synthesizing artepillin C of claim 1 , wherein after the first reaction step, a first purification step is further comprised:
in an acidic environment, the first reaction product is extracted with ethyl acetate to obtain a first crude extract, and then the first crude extract is purified by normal phase column chromatography to obtain the intermediate of artepillin C with a purity of above 95%.
4. The method for synthesizing artepillin C of claim 3 , wherein the product yield of the intermediate of artepillin C after purification is above 35%.
5. The method for synthesizing artepillin C of claim 1 , wherein after the second reaction step, a second purification step is further comprised:
in an acidic environment, the second reaction product is extracted with ethyl acetate to obtain a second crude extract, and then the second crude extract is purified by normal phase column chromatography to obtain artepillin C with a purity of above 95%.
6. The method for synthesizing artepillin C of claim 5 , wherein the product yield of artepillin C after purification is above 35%.
7. A method for synthesizing an intermediate of artepillin C, which comprises the following steps:
a reaction step: in the presence of a base initiator, a compound A shown in formula I and 3,3-dimethylallyl bromide are mixed in a solvent including at least one selected from toluene, dimethylformamide, tetrahydrofuran, and dimethylsulfoxide to lead a reaction in an ice bath continuously for 72 hrs, and then water is poured into the reaction solution to stop the reaction to generate an intermediate of artepillin C shown in formula II;
in which R is C 1-6 alkyl; wherein
the molar ratio of the compound A to 3,3-dimethylallyl bromide is 1:2, the molar ratio of the compound A to the base initiator is 1:2; and
the reaction is carried out in a vacuum environment with argon.
8. The method for synthesizing an intermediate of artepillin C of claim 7 , wherein after the reaction step, a purification step is further comprised:
in an acidic environment, the reaction mixture obtained by completing the reaction step is extracted with ethyl acetate to obtain a crude extract, and then the crude extract is purified by normal phase column chromatography to obtain the intermediate of artepillin C with a purity of above 95%.
9. The method for synthesizing an intermediate of artepillin C of claim 7 , wherein the base initiator is sodium hydride.
10. The method for synthesizing an intermediate of artepillin C of claim 7 , wherein the product yield of the intermediate of artepillin C is above 35%.