SYNTHESIS OF DERIVATIVES OF FERULIC ACID

Ferulie acid is an ingredient of "Dang-Gui" (Angelica sinensis (Oliv.) Diels) and "Chuan Xiong" (Ligusticum wellichit Franch) which had been used for the treatment of thrombotic diseases in traditional Chinese medicine. Three types of derivatives related to ferulie acid have been synthesized. They are alkamine esters of ferulie acid (compounds Ⅰ_1～9), 5-amino-methyl ferulic acids (compounds Ⅱ_5～8) and bisferulie acid ethers (compounds Ⅲ_6～9).Compounds (Ⅰ_1～6) were synthesized from 4-0-carbethoxy-ferulie acids by treatment with thionyl chloride to give acid chlorides which were esterified with various amino-alcohols.Compounds (Ⅰ_7～9) were obtained by treatment of compounds (Ⅰ_1,3,4) with aminoethanol.Compounds (Ⅱ_5～8) were prepared from vanillin which underwent Mannich Reaction to provide the intermediates, 5-substituted-amino-methyl-4-hydroxy-3-methoxybenzaldehydes, followed by condensation with malonie acid in pyridine to yield various 5-substituted-amino-methyl-ferulic acids.Vanillin was reacted with dibromopropane-(1,3), dibromohexane-(1,6) or xylylene bromide to form the corresponding ethers.Compounds Ⅲ_1～4 underwent Knoevenagel Reaction to form derivatives of bisferulie acid ether (Ⅲ_6～8). Vanillin was treated with 3-chloro-1,2-epoxypropane in dilute sodium hydroxide solution to form bis-vanillin-glycerin ether (Ⅲ₄) which reacted with malonic acid in pyridine to afford bisferulie acid-glycerin ether (Ⅲ₉).Preliminary pharmacological results showed that compounds in the (Ⅰ)series inhibited rat platelet aggregation in vitro at concentration much lower than that of ferulie acid itself.