The Synthesis Of Resveratrol

Resveratrol,a kind of unflavonoid polyphenol compounds containing stilbenoid scaffold,possesses apparent pharmacological activity and health care function.It is widely applied in pharmaceuticals,foods,health care products and cosmetics.So it is necessary to develop a green and economic synthetic route.In this study,the synthetic routes and reaction conditions of resveratrol are analyzed and optimized based on a large of reports.Firstly,benzyl 3,5-dibenzyloxybenzoate was prepared by esterification,etherification of 3,5-dihydroxy benzoic acid,and 4-benzyloxybenzaldehyde was prepared by etherification of 4-hydroxybenzaldehyde.Then benzyl 3,5-dibenzyloxybenzoate was reduced to produce 3,5-dibenzyloxybenzyl alcohol by sodium borohydride.3,5-dibenzyloxybenzyl chloride was synthesized by reaction of 3,5-dibenzyloxybenzyl alcohol with thionyl chloride.3,5-dibenzyloxybenzylmethane sulfonate was synthesized by reaction of 3,5-dibenzyloxybenzyl alcohol with methylsulfonyl chloride.Diethyl?3,5-dibenzyloxybenzyl?phosphonatecouldbepreparedbyreactionof3,5-dibenzyloxybenzylchloride,3,5-dibenzyloxybenzylmethanesulfonateor3,5-dibenzyloxybenzyl alcohol with ethyl phosphine.The total yield of diethyl?3,5-dibenzyloxybenzyl?phosphonate from 3,5-dibenzyloxybenzyl alcohol is 35.1%,72.1%,80.0%in these respective three methods.1-?3,5-benzyloxystyryl?-4-benzyloxybenzene was synthesized by reaction of diethyl?3,5-dibenzyloxybenzyl?phosphonate with4-benzyloxybenzaldehyde in the alkaline solution with yield of 97.0%.The de-benzyl reaction of 1-?3,5-benzyloxystyryl?-4-benzyloxybenzene can be promoted by Pd/C and Ni/C through the hydrogenolysis reaction.Unfortunately,the double bond between two phenyl groups also reduced at same time to give hydrogenated Resveratrol.Under promotion of AlCl₃ the debenzyl reaction was very slow to give complex mixture.No reactions occurred using hydrochloric acid,hydrobromic acid and hydrogen bromide as a catalyst.Under promotion of perchloric acid,the protonation of double bond and Friedel-crafts alkylation reaction was occurred to give lousy mixture.Using isooctyl alcohol as solvent,three benzyloxy resveratrol reacted with pyridine hydrochloride to produce resveratrol with yield of 72.7%.And 3,5-benzyl was also found to be more easier to deprotect than 4?-benzyl group.After optimization,through the process containing wittig-horner reaction using 3,5-dihydroxy benzoic acid and 4-Hydroxybenzaldehyde as basic starting material,resveratrol can be prepared with a total yield of 53.4%.Additionally,two other routes were tested unsuccessful.The routes are as follow:1)Claisen condensation reaction between methyl 3,5-bis?benzyloxy?benzoate and methyl4-benzyloxyphenylacetate was not occurred under the sodium hydride,the only observed reaction was self-condensation of methyl 4-benzyloxyphenylacetate.2),Perkin condensationreactionbetween3,5-dibenzyloxybenzaldehydewithsodium4-benzyloxyphenylacetate was not occurred using L-proline as the catalyst.And cross condensation of 3,5-dibenzyloxybenzaldehyde with methyl 4-benzyloxyphenylacetate using sodium ethoxide as a catalyst was also failed to Cannizzaro product of3,5-dibenzyloxybenzaldehyde.