对苯二酚的氨基酸缀合物的合成、表征及美白活性

以新药设计原理中的拼合原理为指导,将对苯二酚一侧酚羟基与具有生物活性的氨基酸进行偶联,以期得到活性更好、毒性更低的对苯二酚氨基酸缀合物。 将对苯二酚的一侧酚羟基进行保护得到对苄氧基苯酚,将氨基被保护的氨基酸与其酚羟基进行偶联,去掉保护基后得到8种对苯二酚的氨基酸缀合物。 在对苄氧基苯酚的酚羟基上引入乙酸连接片段,与氨基酸甲酯盐酸盐进行偶联,去掉保护基后得到8种对苯二酚的氨基酸缀合物。 通过IR、¹H NMR、¹³C NMR和ESI-MS等技术手段对所合成的16种氨基酸缀合物进行了结构表征。 对目标产物进行了美白活性研究。 结果表明,化合物HQ-3b、HQ-3c、HQ-4a、HQ-4b、HQ-7c和HQ-8a对酪氨酸酶的抑制作用优于阳性对照物α-熊果苷(IC₅₀=3.60),其中HQ-4b的IC₅₀值低至0.15,有望成为新型化妆品美白剂。

Synthesis,Characterization and Whitening Activity ofAmino Acid-hydroquinone Conjugates

Based on the piecing together principle in the drug design, we directly couple the hydroxyl group of lead compounds with bioactive compounds in order to get hydroquinone derivatives with high efficiency and low toxicity. 4-(Benzyloxy)phenol was synthesized through the protection of phenolic hydroxyl group, and then coupled with amino acid whose amino group was protected. Moreover, we introduced carboxylic acid moeity into 4-(benzyloxy)phenol and coupled it with amino acid methyl ester hydrochloride. After the removal of the benzyl protecting group, sixteen amino acid-hydroquinone conjugates were synthesized. The sixteen conjugates were characterized by IR, 1H NMR, 13C NMR and ESI-MS. The study of whitening activity of these conjugates showed that HQ-3b, HQ-3c, HQ-4a, HQ-4b, HQ-7c and HQ-8a had significant inhibition to tyrosinase(IC₅₀=3.60) with the IC50 of HQ-4b as low as 0.15.