title: Depigmenting activity of new kojic acid derivative obtained as a side product in the synthesis of cinnamate of kojic acid.
abstract: We synthesized cinnamate derivatives of kojic acid for use as depigmenting agents by various esterification methods. The cinnamate of 5-position of kojic acid (6) was obtained by EDC coupling, DCC coupling, acid chloride, and mixed anhydride methods. To obtain the cinnamate of the 2-position of kojic acid (7), we carried out the nucleophilic addition of the potassium salt of cinnamic acid to kojyl chloride. In this reaction, we discovered the occurrence of a side reaction and identified the structure of the side product thus formed. We evaluated the depigmenting activities of both the side product and the cinnamate derivatives of kojic acid. Interestingly, the side product (11) showed more potent depigmenting activity (IC(50)=23.51μM) than compound 7 (IC(50)>100μM) which is the mother compound of the side product. However, it has no tyrosinase inhibitory activity. Compound 6, the cinnamate of 5-position of kojic acid, also showed moderate depigmenting activity (IC(50)=46.64μM) without tyrosinase inhibitory activity. Production of this side product (11) may have originated from the proton exchange between the potassium salt of cinnamic acid and kojyl chloride. We then efficiently reduced the yield of the side product by controlling the equilibrium of the potassium salt of cinnamic acid. The addition of cinnamic acid greatly reduced the amount of the side product produced.
authors.affiliation: Division of Chemical Engineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Jun-Cheol
authors.initials: JC
authors.lastname: Cho
authors.forename: Ho Sik
authors.initials: HS
authors.lastname: Rho
authors.forename: Heung Soo
authors.initials: HS
authors.lastname: Baek
authors.forename: Soo Mi
authors.initials: SM
authors.lastname: Ahn
authors.forename: Byoung Young
authors.initials: BY
authors.lastname: Woo
authors.forename: Yong Deog
authors.initials: YD
authors.lastname: Hong
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Cheon
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Heo
authors.forename: Song Seok
authors.initials: SS
authors.lastname: Shin
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.forename: Kyung-Do
authors.initials: KD
authors.lastname: Suh
mesh_terms: D000818:Animals; D002460:Cell Line; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010858:Pigmentation / Q000187:drug effects*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002934:Cinnamates; D008543:Melanins; D011753:Pyrones; C029010:cinnamic acid; C011890:kojic acid; D014442:Monophenol Monooxygenase