新型龙胆酸衍生物的合成及其抑制酪氨酸酶活性研究

Synthesis and Inhibition of Tyrosinase Acitivity of New Gentisic Acid Derivatives

为发现新型的美白活性化合物,以龙胆酸甲酯、卤代烃和α-羟基酸乙酯为原料,合成了10个未见文献报道的2-羟基-5-烷(H)氧基苯甲酸酯类衍生物(3a,3b和6a～6h),其结构经1H NMR,IR,MS和HRMS确认.初步生物活性测试结果表明6a,6b,6e和6f具有较强的抑制酪氨酸酶活性,进一步药理实验表明经取代改造后的6a～6h,其毒性和光学毒性都相对龙胆酸甲酯和氢醌更低.

To discover new whitening active compounds, ten novel 2-hydroxy-5-alkyl（H）oxybenzoic ester derivatives （3a, 3b and 6a-6h） were prepared via the starting materials of methyl gentisate, alkyl halides and a-hydroxy acid ethyl ester. Their chemical structures were confirmed by ^1H NMR, IR, MS and HRMS techniques. The preliminary bioassay test demonstrated that compounds 6a, 6b, 6e and 6f had stronger inhibition of tyrosinase activity. Further pharmacological experiments showed that after substitution modification of compounds 6a-6h, their toxicity and phototoxicity are lower than methyl gentisate and hydroquinone.