アスコルビン酸誘導体の創製とその医薬品開発応用への可能性（日本薬学会第136回シンポジウム「ビタミンのケミカルバイオロジー研究」）

抄録

L-Ascorbic acid (AsA), known as vitamin C, plays key roles in many biological processes such as collagen formation, carnitine synthesis, and iron absorption. AsA is also an important antioxidant in food and biological systems, but it is unstable under various oxidative conditions, resulting in its rapid degradation. 2-O--D-Glucopyranosyl-L-ascorbic acid (AA-2G), a stable AsA derivative, has been developed to achieve an efficient action as an AsA source, a pro-vitamin C agent. AA-2G has been approved by the Japanese Government as a quasi-drug principal ingredient in skin care and as a food additive. AA-2G is now widely used as a medical additive in commercial cosmetics. This stable AsA derivative exhibits vitamin C activity in vitro and in vivo after enzymatic hydrolysis to AsA by -glucosidase. Recently, we have synthesized two types of monoacylated derivatives of AA-2G, 6-O-acyl-2-O--D-glucopyranosyl-L-ascorbic acids having a straight-acyl chain of varying length from C4 to C18 (6-sAcyl-AA-2G) and a branched-acyl chain of varying length from C6 to C16 (6-bAcyl-AA-2G), in order to improve the bioavailability of AA-2G and have indicated that 6-sAcyl-AA-2G and 6-bAcyl-AA-2G exert usually known vitamin C functions efficiently in vitro and in vivo. More recently, we found that, unexpectedly, 6-sAcyl-AA-2G per se had antiallergic activity based on a degranulation inhibiting action and that a 6-O-acyl AsA, an intermediate in the hydrolysis of 6-bAcyl-AA-2G to AsA, showed a significant antitumor activity in tumor-bearing mice. In this review, the author presents a possible application of created AsA derivatives to drug development.