Method for synthesizing xanthohumol
A method for synthesizing xanthohumol (XN) from naringenin comprising includes the steps of acylating hydroxyl groups of a naringenin flavone moiety to obtain an acylation product, a reaction of conversion of the flavone moiety into a chalcone moiety, and subjecting the chalcone compound to a reaction of hydrolysis of its ester groups, and next to a reaction of substitution of a prenyl moiety of the chalcone moiety to obtain xanthohumol. The xanthohumol produced by this method can be purified using crystallisation.
1 . A method for synthesizing xanthohumol (XN), the method comprising the steps of:
providing naringenin,
acylating hydroxyl groups at carbons 7 and 4′ of a naringenin flavone moiety to obtain an acylation product,
subjecting the acylation product to a reaction of alkylation of a free hydroxyl to an alkoxyl moiety and to a reaction of conversion of the naringenin flavone moiety into a chalcone moiety, in a presence of a non-nucleophilic base, in a polar aprotic solvent, to obtain a chalcone compound,
subjecting the chalcone compound to:
a reaction of hydrolysis of its ester groups at carbons 4, 4′ and 6 of the chalcone moiety to obtain hydroxyl groups, and next
a reaction of substitution of a prenyl moiety at carbon 5′ of the chalcone moiety to obtain xanthohumol.
2 . The method according to claim 1 , comprising carrying out the step of acylating using acetic anhydride.
3 . The method according to claim 1 , comprising purifying the acylation product by way of crystallisation.
4 . The method according to claim 1 , comprising carrying out the reaction of alkylation using an alkylating agent selected from a group consisting of C1-C8 alkyl iodides and bromides.
5 . The method according to claim 4 , comprising carrying out the reaction of alkylation using the alkylating agent selected from a group consisting of methyl iodide and methyl bromide.
6 . The method according to claim 1 comprising carrying out the reaction of conversion of the flavone moiety into the chalcone moiety in a presence of a non-nucleophilic base selected from a group consisting of: 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO) and 4-(N,N-dimethylamino) pyridine (DMAP).
7 . The method according to claim 1 , comprising carrying out the reaction of conversion of the flavone moiety into the chalcone moiety in a polar aprotic solvent selected from a group consisting of: dimethylformamide (DMF), N-methylpyrrolidone (NMP) and dimethylacetamide (DMAc).
8 . The method according to claim 1 , comprising subjecting the obtained chalcone compound to a hydrolysis reaction carried out using ethyl alcohol in an alkaline medium.
9 . The method according to claim 1 , comprising carrying out the substitution reaction of the prenyl moiety using a prenylating agent comprising 1,1-dimethylallyl moiety.
10 . The method according to claim 9 wherein the prenylating agent used is 1,1-dimethylallyl alcohol or acetic acid ester of 1,1-dimethylallylalcohol.
11 . The method according to claim 1 , comprising carrying out the substitution reaction of the prenyl moiety in the presence of boron trifluoride etherate (BF 3 ·O(CH 2 CH 3 ) 2 ) in dioxane, at elevated temperature.
12 . The method according to claim 11 , comprising carrying out the substitution reaction at a temperature of 40° C.