SYNTHESIS OF DERIVATIVES OF FERULIC ACID
MO Ruo-Ying, SHAO Guo-Xian, ZHU Li-Lian and HE Wen-Yi(Department of Organic Synthesis, Institute of Materia Medcea, Chinese Academy of Medical Sciences, Beijing)
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 (Ⅲ_4) which reacted with malonic acid in pyridine to afford bisferulie acid-glycerin ether (Ⅲ_9).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.