title: New synthesis of artepillin C, a prenylated phenol, utilizing lipase-catalyzed regioselective deacetylation as the key step.
abstract: We have synthesized artepillin C, a diprenylated p-hydroxycinnamate originally isolated from Brazilian propolis and exhibiting antioxidant and antitumor activities, from 2,6-diallylphenol. Replacement of the terminal vinyl with 2,2-dimethylvinyl group by olefin cross-metathesis and subsequent transformation yielded 2,6-diprenyl-1,4-hydroquinone diacetate. Candida antarctica lipase B-catalyzed deacetylation in 2-propanol regioselectively removed the less hindered acetyl group to give 2,6-diprenyl-1,4-hydroquinone 1-monoacetate. After triflation of the liberated 4-hydroxy group, a three-carbon side chain was introduced by palladium-mediated alkenylation with methyl acrylate. Final hydrolysis of the esters furnished artepillin C.
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Science , Keio University , Tokyo , Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yashiro
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Science , Keio University , Tokyo , Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Hanaya
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Science , Keio University , Tokyo , Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shoji
authors.affiliation: a Faculty of Pharmacy, Department of Pharmaceutical Science , Keio University , Tokyo , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugai
mesh_terms: D000107:Acetylation; D000840:Anisoles / Q000737:chemistry; D055162:Biocatalysis; D060326:Chemistry Techniques, Synthetic; D005656:Fungal Proteins / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D019800:Phenol / Q000138:chemical synthesis* / Q000737:chemistry*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry*; D054876:Prenylation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000840:Anisoles; D005656:Fungal Proteins; D010666:Phenylpropionates; D019800:Phenol; C009760:mequinol; C102259:artepillin C; D008049:Lipase; C431349:lipase B, Candida antarctica
keywords: artepillin C; lipase; prenylated phenol; regioselective transesterification