title: Enzymatic synthesis of caffeic acid phenethyl ester analogues in ionic liquid.
abstract: An efficient procedure for transesterification of methyl caffeate was developed to produce caffeic acid phenethyl ester analogues with Candida antarctica lipase B using an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, as a solvent. The system provided 48.8mM 2-cyclohexylethyl caffeate and 46.9 mM 3-cyclohexylpropyl caffeate with conversion yields of 97.6% and 93.8%, respectively. Reusability of the system was investigated, and the yield of 4-phenylbutyl caffeate was increased from 30.4 to 45.7 mM when the transesterification was carried out under reduced pressure to remove a by-product, methanol. Additionally, we showed that both 2-cyclohexylethyl caffeate and 3-cyclohexylpropyl caffeate exhibit strong antiproliferative activities, which are comparable to that of 5-fluorouracil by MTT assay.
authors.affiliation: Graduate School of Applied Biological Chemistry, Kinki University, 3327-204 Nakamachi, Nara City, Nara 631-8505, Japan. kurata090401@nara.kindai.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurata
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Shiori
authors.initials: S
authors.lastname: Irie
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takemoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Akai
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirota
authors.forename: Tokio
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwai
authors.forename: Mina
authors.initials: M
authors.lastname: Furusawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kishimoto
mesh_terms: D002109:Caffeic Acids / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017743:Equipment Reuse; D004951:Esterification; D005656:Fungal Proteins; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry; D008049:Lipase / Q000378:metabolism*; D000432:Methanol / Q000737:chemistry / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011312:Pressure; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: C493485:1-butyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)amide; D002109:Caffeic Acids; D005656:Fungal Proteins; D007093:Imidazoles; D052578:Ionic Liquids; D013449:Sulfonamides; C042405:methyl caffeate; D008049:Lipase; C431349:lipase B, Candida antarctica; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D000432:Methanol