Synthesis of 3-cyclohexylpropyl caffeate from 5-caffeoylquinic acid with consecutive enzymatic conversions in ionic liquid

We developed a convenient one-pot procedure for conversion of 5-caffeoylquinic acid to 3-cyclohexylpropyl caffeate, which exhibits an antiproliferative effect toward various human tumor cells. The procedure was comprised of two consecutive reactions by chlorogenate hydrolase (EC 3.1.1.42) from Aspergillus japonicus and Candida antarctica lipase B, and was performed using an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, as the reaction solvent. When various caffeoylquinic acids from coffee beans, namely, 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid were used, the first alcoholysis reaction with methanol using chlorogenate hydrolase produced methyl caffeate with conversion yields of 60.0%, 61.3%, 86.0%, 92.7%, and 114.0%, respectively, to each individual substrate. Two caffeoyl groups of dicaffeoylquinic acids would be used for the synthesis of methyl caffeate. In the subsequent transesterification reaction by C. antarctica lipase B with 3-cyclohexyl-1-propanol, the methyl caffeate produced was converted to 3-cyclohexylpropyl caffeate under reduced pressure to remove the by-product methanol. In the one-pot synthesis, the methyl caffeate was transesterified efficiently to 3-cyclohexylpropyl caffeate by C. antarctica lipase B with deactivation of chlorogenate hydrolase by taking advantage of the difference between the optimum temperatures for the two enzymes. This system provided 12.8 mM 3-cyclohexylpropyl caffeate from 15 mM 5-caffeoylquinic acid with conversion yield of 85.3%.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► 5-Caffeoylquinic acid (1) was converted to 3-cyclohexylpropyl caffeate (3). ► The procedure was comprised of consecutive enzymatic conversions in [BMIM][NTf2]. ► Chlorogenate hydrolase from Aspergillus japonicus acted on 5-caffeoylquinic acid (1). ► Candida antarctica lipase B acted on methyl caffeate (2).