Regioselective Enzymatic Synthesis of Kojic Acid Monoesters

Abstract

Kojic acid is a fungal metabolite and one of the strongest tyrosinase inhibitors. Its esters are used as lipid-compatible skin whitening components in cosmetic formulations. In this study, lipase PS, lipase AK, Lipolyve AN and pig pancreatic lipase catalyzed the acetylation of kojic acid under selective formation of the same product, kojic 7-acetate. However, the enzymes differed in their regioselectivity when catalyzing the alcoholysis of kojic acid diacetate. While lipase PS and lipase AK produced mixtures of both monoacetate regioisomers (7-acetate and 5-acetate of kojic acid), the pancreatic lipase almost exclusively produced 5-acetate. The enzyme displayed the same regioselectivity in the palmitoylation of kojic acid and in the alcoholysis of kojic acid dipalmitate. Simple reaction engineering with PPL as a catalyst thus provides the complementary monoesters of kojic acid. Kojic 7-acetate, 5-acetate, 7-palmitate and 5-palmitate were prepared with yields after purification of 57.3%, 38.2%, 31.7% and 31.4%, respectively.

Nanotechnology-Enhanced Cosmetic Application of Kojic Acid Dipalmitate, a Kojic Acid Derivate with Improved Properties

“…The esterification process involves removing the OH group and attaching the fatty acid (R) to create KA monoesters like 5-O-KA monoesters and 7-O-KA monoesters. Fatty acids have been synthesized chemically and enzymatically to link with KA at positions C-5 and C-7 [74]. Chemical esterification of KA oleate was facilitated by N,N ′ -dicyclohexylcarbodiimide (DCC)/4-dimethylaminopyridine (DMAP) in dichloromethane, resulting in yields of up to 80% within 24 to 48 h. However, this method necessitates the use of environmentally harmful and dangerous chemicals, requiring additional safety precautions.…”

Production of Kojic Acid by Aspergillus niger M4 with Different Concentrations of Yeast Extract as a Nitrogen Source

“…In cosmetics, it has been used as a skin-lightening agent [9,10] as it is a copper chelator and inhibits the activity of tyrosine containing copper ions at the active site, forming a KA-Cu-Tyrosine complex, which reduces enzyme activity in human cells by reducing melanin content [6,8]. KA (5hydroxy−2-hydroxymethyl-γ-pyrone) is a secondary metabolite produced by a wide range of fungi of the genus Aspergillus, such as A. terreus [11], A. parasiticus, and A. flavus [12]; fungi of the genus Penicillium; and certain bacteria [13]. A prominent strain is Aspergillus oryzae [14], called 'koji-kin' in Japanese, which is the origin of the common name of this organic acid [15].…”