Morisaki K, Ozaki S
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama, Japan.
Chem Pharm Bull (Tokyo). 1996 Sep;44(9):1647-55. doi: 10.1248/cpb.44.1647.
Novel hybrid L-ascorbic acid (vitamin C) derivatives with other biologically active substances, 5-hydroxy-2-hydroxymethyl-beta-pyrone (kojic acid) and alpha-tocopherol (vitamin E), linked at the C-2 or C-3 hydroxyl group were synthesized, and their thermal stability and inhibitory effects on tyrosinase activity, active oxygen species (AOS), and free radicals were estimated in vitro. It was found that a hydrophilic derivative, 2-O-(5-hydroxy-4H-pyran-4-one-2-methyl)-L-ascorbic acid (1), exhibited good thermal stability and inhibitory activities against tyrosinase catalyzed melanin formation, AOS, and free radicals compared to vitamin C and its conventional derivatives (such as the 2-phosphate 6-stearate and 2.6-dipalmitate, and 2-O-octadecylascorbic acid), as well as vitamin E, kojic acid, and arbutin. It is apparent that 1 has the biological properties of vitamin C and kojic acid, and acts synergistically. The hydroxyl groups at the C-3 position of the vitamin C moiety and the C-5 position of the kojic acid moiety are critical for the biological activities. We consider that the kojic acid moiety of 1 counterbalances the diminution of the biological activity due to shielding of the biologically important C-2 hydroxyl group of the vitamin C moiety. In addition, the thermal stability was significantly improved relative to not only vitamin C but also kojic acid. Further, a lipophilic derivative, 3-O-[(alpha-tocopheryloxy)-2-hydroxypropyl]-L-ascorbic acid, 2, was far more stable than vitamin C and its typical lipophilic derivatives. Compound 2 exhibited almost the same inhibitory activities against tyrosinase-catalyzed melanin formation, AOS, and free radicals as typical lipophilic derivatives, although these biological activities of 2 were lower than those of vitamin C.
合成了新型杂化L - 抗坏血酸（维生素C）衍生物，其与其他生物活性物质5 - 羟基 - 2 - 羟甲基 - β - 吡喃酮（曲酸）和α - 生育酚（维生素E）在C - 2或C - 3羟基处相连，并在体外评估了它们的热稳定性以及对酪氨酸酶活性、活性氧（AOS）和自由基的抑制作用。结果发现，一种亲水性衍生物2 - O -（5 - 羟基 - 4H - 吡喃 - 4 - 酮 - 2 - 甲基）- L - 抗坏血酸（1），与维生素C及其传统衍生物（如2 - 磷酸6 - 硬脂酸酯、2,6 - 二棕榈酸酯和2 - O - 十八烷基抗坏血酸）以及维生素E、曲酸和熊果苷相比，表现出良好的热稳定性，并且对酪氨酸酶催化的黑色素形成、AOS和自由基具有抑制活性。显然，1具有维生素C和曲酸的生物学特性，并具有协同作用。维生素C部分的C - 3位羟基和曲酸部分的C - 5位羟基对其生物学活性至关重要。我们认为化合物1的曲酸部分抵消了由于维生素C部分重要的C - 2羟基被屏蔽而导致的生物活性降低。此外，其热稳定性不仅相对于维生素C而且相对于曲酸都有显著提高。此外，一种亲脂性衍生物3 - O - [（α - 生育酚氧基）- 2 - 羟丙基] - L - 抗坏血酸（2）比维生素C及其典型的亲脂性衍生物稳定得多。化合物2对酪氨酸酶催化的黑色素形成、AOS和自由基的抑制活性与典型的亲脂性衍生物几乎相同，尽管其这些生物学活性低于维生素C。
