Synthesis Anti-HIV Active Ingredients Of Arnebia Euchroma PHDF Intermediates And Activity Screening

Objective: Synthesis Anti-HIV active ingredients of Arnebia euchroma PHDF（2-(4’-hydroxy-3’-methoxy-phenyl)-3-(hydroxymethyl)-6-methoxy-2,3-dihydro-benzofuran-5-formicacid）intermediates and Activity screening. Methods:1. Using vanillinand4-hydroxy-2-methoxybenzaldehyde as raw material, to synthetic key intermediatecompound4[2-(3-methoxy-4-hydroxyphenyl)-3-methoxycarbonyl-5-methoxycarbonylvi-nyl-6-methoxy-2,3-dihydro-benzofuran],with the Knoevenagel condensation, esterificati-on,cross-oxidation coupling method.2. Screening of the preparation methods and reactionconditions for intermediate compound8[(E)3-(4-hydroxy-2-methoxyphenyl) acrylate].3.Investigat the effect of silver oxide, lead dioxide, potassium ferricyanide, anddi-tert-butyl peroxide, four different oxidant on the yied for compound4in the oxidativecoupling reaction.4. Investigation on inhibitory activity of intermediate compound againstHIV-1protease, the integrase enzyme HIV-1and the HIV-1reverse transcriptase. Results:1. the optimization of intermediate compound8were the compound9[(E)-3-(4-hydroxy-2-methoxyphenyl)-acrylic acid] and dehydrationagent EDC HCl (1:1.5)conditions,40℃reaction4h, the yield was67%.2. The lead dioxide has the better effectin the four kinds of oxidants with yied38%.3. Synthesis of6intermediate compound，respectively Compound6:(E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid, Compound7:(E)-3-(4-hydroxy-3-meth-oxyphenyl)acrylate, Compound9:(E)-3-(4-hydroxy-2-methox-yphenyl)acrylic acid, Compound8:(E)-3-(4-hydroxy-3-methoxyphenyl)acrylate, Comp-ound11:2-(3-methoxy-4-hydroxy-phenyl)-3-methoxycarbonyl-5-acrylic acid-6-methoxy-2,3-dihydro-benzofuran and Compound4：2-(3-methoxy-4-hydroxyphenyl)-3-methoxy-carbonyl-5-acrylate-6-methoxy-2,3-dihydro-benzofuran.4. At50μg/ml, the compound4inhibitory activity show relatively strong activity in the anti-HIV-1protease; The IC50ofcompound4was68.3%, slightly stronger than the other compounds, compared to positive drug inhibition remains weak in the anti-HIV-1reverse transcriptase; six compounds hadno inhibitory effect, in the anti-HIV-1integrase enzyme studies. Conclusion: Successfulpreparation of the intermediate compound4with oxidative coupling reaction and fiveother compounds. Synthesis of the intermediate compound4and11(containingDihydrobenzofuran skeleton) have a certain extent inhibitory effect on HIV-1protease;Preliminary structure-activity shows, compound6,9esterified of anti-HIV proteaseinhibitory activity enhanced.