Antiallergic Activity of 3-O-Dodecyl-l-ascorbic Acid.

2-O-Alkyl-l-ascorbic acids and 3-O-alkyl-l-ascorbic acids were synthesized, and their degranulation inhibitory activities were evaluated. Among ascorbic acid derivatives with butyl, octyl, dodecyl, hexadecyl, and octadecyl groups introduced at the C-2 or C-3 positions, an AA derivative with a dodecyl group introduced at the C-3 position, 3-O-dodecyl-l-ascorbic acid (compound 8), showed the strongest inhibitory activity against antigen-stimulated degranulation. Compound 8 also inhibited calcium ionophore-stimulated degranulation. Compound 11, in which the hydroxyl group at the C-6 position of compound 8 was substituted with an amino group, and compound 12, in which the dodecyloxy group at the C-3 position of compound 8 was exchanged with a dodecylamino group, were synthesized, and these derivatives showed weaker inhibitory activity against antigen-stimulated degranulation than that of compound 8. In addition, orally administered compound 8 inhibited passive cutaneous anaphylaxis reactions in mice with a potency equal to that of oxatomide, an antiallergic agent. These results suggest that compound 8 may be a candidate for antiallergic treatment.

Synthesis of Ascorbic Acid Derivatives with Different Types of C8 Straight Acyl Chain and Their Neurite Outgrowth-Enhancing Activities.

We previously reported that 2-O-α-D-glucopyranosyl-6-O-octanoyl-L-ascorbic acid, having a C8 straight acyl chain, at a concentration of 100 µM remarkably enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells after being metabolized to L-ascorbic acid (AA) as an active form by esterase and α-glucosidase. In this study, to examine the structure-activity relationship of 6-O-substituted AA derivatives with a C8 straight acyl chain for neurite outgrowth-promoting activity, we synthesized AA derivatives 1-4 and compared their activities for promoting NGF-induced neurite outgrowth in PC12 cells. AA derivatives 1-4 showed neurite outgrowth-enhancing activity at 100 µM, while AA derivative 2 also showed the enhancing activity at 3 µM. Furthermore, AA derivative 2 as well as AA enhanced NGF-induced neurite outgrowth after being incorporated into PC12 cells via sodium-dependent vitamin C transporter as an anion transporter. The results suggested that AA derivative 2 has neurite outgrowth-enhancing activity in its intact form at a low concentration (3 µM) and that AA derivatives 1-4 showed their activities in the form of AA, a metabolite of these derivatives, at a higher concentration (100 µM).