Kojic acid derivatives

From the bacteriostatic activity data of kojic acid derivatives determined at pH 6, 7, and 8 with s. aureus, we have derived the following equations (13). 

Another ingenious route for the generation of the dipolar species involves the carbonyl-0-alkylation or 0-silylation of 3-oxygenated 4-pyrones. The example below shows 0-methylation of a kojic acid derivative, then deprotonation of the 3-hydroxyl using a hindered base to trigger the dipolar cycloaddition. 

To the solution of 5.31 g benzaldehyde (0.05 mol) and 4.66 g aniline (0.05 mol) in 50-100 mL 95% ethanol was added 7.11 g kojic acid. The mixture was stoppered and allowed to stand for 1 week, while the kojic acid derivatives precipitated within 1 day. The solid was Altered and washed, then puriAed by recrystaUization from ethanol to afford 13.58 g of the Betti amine, in a yield of 84%, m.p. 176°C. 

Some studies on synthetic kojic acid derivatives... 

Recently, it was foimd that kojic add-tripeptide amides showed similar tyrosinase inhibitoiy activities to those of kojic add-tripeptide free adds but exhibited superior storage stability than those of kojic acid and kojic add-trip>eptide free acids (Noh, 2007). To find further kojic acid derivatives with higher tyrosinase inhibitory activity, stability, and synthetic effidency, a library of kojic add-amino acid amides (KA-AA-NH2) prepared and screened for their tyrosinase inhibitoiy activities. It was also confirmed that the kojic add-phenylalanine amides reduced the amount of dopachrome production during the melanin formation. It was suggested that a tyrosinase inhibition mechanism of KA-AA-NH2 based on the possible hydrophobic interadions between the side chain of KA-AA-NH2 and tyrosinase active site by a docking program (Noh, 2009 Kim, 2004). 

Fig. 3. Chemical structure of some synthetic kojic acid derivatives as tyrosinase inhibitors.

Kojic acid is currently used as tyrosinase inhibitors which are commercially available. Unfortunately, unstabiUty during storage limits its use and new tyrosinase inhibitors of novel kojic acid derivatives are needed in cosmetics industry. More expended studies on this subject will be helpful in designing more suitable tyrosinase inhibitors for human use. 

Aytemir, M.D., Septioglu, E., Cali / U- (2010a). Synthesis and anticonvulsant activity of new kojic acid derivatives. Arzneim. Forsdi. Drug Res., Vol.60(l), pp.22-29. 

Fickova, M. Pravdova, E. Rondhai, L. Uher, M. Brtko, J. (2008) In vitro antiproliferative and cytotoxic activities of novel kojic acid derivatives 5-benzyloxy-2-selenocyanotomethyl- and 5-methoxy-2- selenocyanotomethyl d-pyranone.. App. Toxicol, Vol.28, p p.554-559. 

Ring Contraction Reactions.—The photochemical rearrangement of the kojic acid derivative (133) via the postulated intermediate (134) gave in low yield the ring-contracted cyclopentenedione (135) which was reduced in situ to terrein (136) (Scheme 43). °°... 

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