Amino Derivatives of Kojic Acid

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

“…Mannich-type reactions are three-component condensation reactions involving carbonyl compounds, existing as keto-enol tautomeric forms, formaline, and a primary or secondary amine. In 1912, Mannich and Krosche were the first to prepare some Mannich bases only at the 6-position; this is the reactive position of kojic acid [25]. Due to its phenol-like properties, kojic acid readily undergoes aminomethylation in the Mannich reaction at room temperature, ortho to the enolic hydroxyl group.…”

“…Due to its phenol-like properties, kojic acid readily undergoes aminomethylation in the Mannich reaction at room temperature, ortho to the enolic hydroxyl group. It is reported that di-Mannich derivatives can be obtained in an acidic medium from kojic acid, formaline, and an aromatic amine [25,26]. Mannich bases of kojic acid derivatives, which show various biological activities, were prepared and evaluated for their activities by different researchers [6 -9, 25, 27].…”

Design, synthesis and in vivo/in vitro screening of novel chlorokojic acid derivatives

“…These three compounds provided basis for our research area. Mannich bases of several hydroxypyranones including kojic acid and pyromeconic acid (3-hydroxy-4H-pyran-4-one) were synthesized before by different researchers 41,42 . They react with amines and formaline like phenols to produce the Mannich base as a result of aminoalkylation of the ortho position of the −OH group.…”

“…On the other hand, although there were two open nuclear positions of kojic acid (3-and 6-), because of its phenollike properties, the reaction occurred only at 6-position and mono-Mannich derivatives were obtained in basic medium (Scheme 3). When the enolic hydroxyl group converted to an ether group, 6-position was deactivated 41 . The mechanisms of this Mannich reaction both in an acidic and a basic medium were investigated and found that, enhanced reactivity in a basic medium is due to increase of the electronegativity at 6-position 42 .…”

Kojic acid in organic synthesis

“…However, reactions with L-asparic acid, L-asparagine, L-glutamic acid, L-glutamine, DL-phenyl alanine, and DL-tyrosine did not occur. In addition, O'Brien et al 82 in 1960 showed that the reaction of KA with secondary amines such as dimethyl and diethyl amine, pyrolidine, morpholine, piperidine, N -methylpiperazine, and 1,2,3,4-tetrahydroquinoline afforded a product similar to 78, but the reaction with lauryl and stearyl amines gave bis-Mannich adducts, similar to 79.…”