Enzymatic synthesis of caffeic acid phenethyl ester analogues in ionic liquid.
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.
Kurata
Atsushi
A
Graduate School of Applied Biological Chemistry, Kinki University, 3327-204 Nakamachi, Nara City, Nara 631-8505, Japan. kurata090401@nara.kindai.ac.jp
Kitamura
Yuki
Y
Irie
Shiori
S
Takemoto
Shintaro
S
Akai
Yoshiaki
Y
Hirota
Yoshitaka
Y
Fujita
Tokio
T
Iwai
Kazuya
K
Furusawa
Mina
M
Kishimoto
Noriaki
N
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*
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