Some New Reactions and Derivatives of Kojic Acid

Abstract

The stability of the ring structure in kojic acid toward various reagents was investigated.Cleavage to an open-chain, dienol derivative in i V s o d i~~m hydroxide a t 25", or fragmentation of the structure, was very slow. The benzoyl group ill the fifth (phenolic) position of dibe~~zoylkojic acid was removed by hydroxy1-amine hydrochloride in pyridine so selectively that the method was of value in synthesizing certain new derivatibes. Although catalytic hydrogenation readily reduced the pyrone ring in kojic acid to undefined substances, zinc dust in glacial acetic acid reduced the hydroxyrnethyl group in the dibenzoate to a methyl group and yielded benzoylallomaltol. The ring in dibe~lzoylkojic acid was apparently opened, with retention of both benzoyl ~~O L I P S , by semicarbazide hydrochloride 2nd pyridine to yield two isomeric "dise~nicarbazones", C?~Hz?Ns07, decomp., 215" and 172-173", respectively. The higher-melting isomer when boiled with dilute acid gave a compoulld C21HljN3Ojr m.p. 241", which was apparently cyclic; the same isomer with nitrous acid yielded two isomeric, apparently open-chain "monosemicarbazones", C2LHleN30,, decomp., 215" and 178-179", respectively. The structures of these five compounds were not determined. The following substances were thought to be new: sodium lcojate, a white powder, and its crystalline tetrahydrate; 5-hydroxy-2-(methoxymethy1)-y-pyrone, m.p. 75-76', and its crystalline aluminum salt, decomp. 270-271"; molecular addition compound of dibenzoyllcojic acid and benzoic acid, m.p. 120-121"; 2-(acetoxyn~ethyl)-5-benzoxy-y-pyrone, m.p. 144"; 2-(benzoxymethy1)--5-hydroxy-y-pyrone, m.p. 180-181"; and 2-(benzoxy1nethyl)-5-rnetho.uy-~-pyrone, 1n.p. 110-111". A more convenient synthesis was discovered for 5-benzoxy-2-(hydroxymethy1)-y-pyrone, and the published melting point was revised from 136" to 1T3-144"; the melting point of 5-benzoxy-2-(triphenylmethoxyrnethy1)-y-pyrone was revised from 206-208" to 213-214O.

Anticonvulsant and Neurotoxicity Evaluation of Some Novel Kojic Acids and Allomaltol Derivatives

“…The hydroxyl group that is directly bound to the pyranone ring was probable more deprotonated than the hydroxymethyl group [19]. Quantum mechanical investigations on tautomeric equilibria of kojic acid were performed.…”

Pyrone derivatives and metals: From natural products to metal-based drugs

“…In this procedure, kojic acid is reacted with thionylchloride, yielding chlorokojic acid and subsequent reduction with zinc in hydrochloric acid affords the desired product (Scheme 1). Although other synthetic pathways are described in literature, e.g., by Beelik and Purves [11], who obtained allomaltol via the reduction of dibenzyl kojic acid with zinc in glacial acetic acid, Yabuta's method is still the most popular [12].…”

Production Technology and Applications of Kojic Acid

“…Reaction of kojic acid molecule with thionyl chloride is given below (Fig. 10) [48,49]. Reduction of chlorokojic acid with zinc dust in concentrated hydrochloric acid results in the production of allomaltol.…”

“…The addition of 5% kojic acid increases the toxicity of nicotine insecticide from 5 to 35% [49,76]. Natural compounds that pose no significant side effects in medicinal or environment field are potential sources of antifungal agents in agriculture either in normal form or as a structural backbone for more effective and efficient organic derivatives.…”