酚类糖苷缀合物的合成、表征及美白活性

doi:10.11944/j.issn.1000-0518.2016.07.160031

摘要/Abstract

摘要：

根据拼合原理,以对苯二酚(p-HQ)、间苯二酚(m-HQ)及邻苯二酚(o-HQ)为先导化合物,通过一侧酚羟基的苄基保护、引入溴乙酸甲酯、还原、与3种糖元偶联、脱除保护基得到9种目标化合物。同样以3-(4-羟基苯基)-1-丙醇为起始物质,通过苄基保护、与3种糖元偶联、脱除保护基得到3种目标化合物。通过IR、¹H NMR、¹³C NMR、HRMS等波谱分析方法对所合成的12种目标化合物进行了结构表征。对合成的酚类糖苷缀合物进行了美白活性研究。结果表明,化合物p-HQ-6a、m-HQ-7a、p-HQ-6b、m-HQ-6b、o-HQ-6b、p-HQ-6c、m-HQ-7c、L-3a和L-4b对酪氨酸酶有抑制作用,其中o-HQ-6b和p-HQ-6c对酪氨酸酶的抑制作用优于阳性对照物α-熊果苷。

关键词: 熊果苷, 糖苷, 美白

Abstract:

Three alcohol intermediates were synthesized through protection of one side phenolic hydroxyl group, coupling with methyl bromoacetate, and reduction using p-dihydroxybenzene, m-dihydroxybenzene and o-dihydroxybenzene as lead compounds. These three intermediates coupled with three different glycogens to get nine targeting compounds. Similarly, we protected phenolic hydroxyl of 3-(4-hydroxyphenyl)-1-propanol, and then coupled it with three different glycogens to yield three target compounds. The twelve target compounds were characterized by IR, ¹H NMR, ¹³C NMR and HRMS. The study of whitening activity of these conjugates shows that compounds p-HQ-6a, m-HQ-7a, p-HQ-6b, m-HQ-6b, o-HQ-6b, p-HQ-6c, m-HQ-7c, L-3a and L-4b have significant inhibition to tyrosinase, among of them compounds o-HQ-6b and p-HQ-6c against tyrosinase are obviously better than the positive control of α-Abutin.

Key words: arbutin, glycoside, whitening activity

李常, 孙竞阳, 支德福, 田甜, 陈艳华, 赵龙铉, 赵春晖. 酚类糖苷缀合物的合成、表征及美白活性[J]. 应用化学, 2016, 33(7): 780-791.

LI Chang, SUN Jingyang, ZHI Defu, TIAN Tian, CHEN Yanhua, ZHAO Longxuan, ZHAO Chunhui. Synthesis, Characterization and Whitening Activity of Glucoside-phenols Conjugates[J]. Chinese Journal of Applied Chemistry, 2016, 33(7): 780-791.

参考文献

[1]	CHEN Qingxi,SONG Kangkang. Progress Tyrosinase[J]. J Xiamen Univ,2006,45(6):731-736(in Chinese). 陈清西,宋康康. 酪氨酸酶的研究进展[J]. 厦门大学学报,2006,45(6):731-736.
[2]	Parvez S,Kang M,Chung H,et al.Survey and Mechanism of Skin Depigmenting and Lightening Agents[J]. Phytother Res,2006,20(11):921-934.
[3]	DING Dapeng. Progress Tyrosinase Inhibitors[J]. J Pract Med,2005,21(12):1364-1366(in Chinese). 丁大鹏. 酪氨酸酶抑制剂研究进展[J]. 实用医学杂志,2005,21(12):1364-1366.
[4]	SONG Kangkang,QIU Ling,HUANG Huang,et al.Arbutin as a Cosmetic Additive Inhibition of Tyrosinase[J]. J Xiamen Univ,2006,42(6):731-736(in Chinese). 宋康康,邱凌,黄璜,等. 熊果甙作为化妆品添加剂对酪氨酸酶抑制作用[J]. 厦门大学学报,2003,42(6):791-794.
[5]	Hsihe P W,Aljuffali I A,Fang C L,et al.Hydroquinone-salicylic Acid Conjugates as Novel Anti-Melasma Actives Show Superior Skin Targeting Compared to the Parent Drugs[J]. J Dermatol Sci,2014,76(2):120-131.
[6]	Hung C F,Chen W Y,Aljuffali I A. The Risk of Hydroquinone and Sunscreen Over-Absorption via Photodamaged Skin is not Greater in Senescent Skin as Compared to Young Skin:Nude Mouse as an Animal Model[J]. Int J Pharm,2014,471(1/2):135-145.
[7]	Lukas Brigitte,Schmiderer Corinna,Mitteregger Ulrike. Arbutin in Marjoram and Oregano[J]. Food Chem,2010,121(1):185-190.
[8]	Nakajima M,Shinoda I,Fukuwatari Y,et al.Arbutin Increases the Pigmentation of Cultured Human Melanocytes Through Mechanisms Other than the Induction of Tyrosinase Activity[J]. Pigm Cell Res,1998,11(1):12-17.
[9]	Piotr Migas,Miroslawa Krauze-Baranowska. The Significance of Arbutin and Its Derivatives in Therapy and Cosmetics[J]. Phytochem Lett,2015,13:35-40.
[10]	SUN Guanzhong,LIU Jingying. The Research on the Chemical Structure of Aspirin in Carbohydrate Modifying[J]. J Tianjin Med Univ,2003,1(9):19-20(in Chinese). 孙关中,刘景英. 糖类修饰阿司匹林化学结构的研究[J]. 天津医科大学学报,2003,9(1):19-20.
[11]	Han G D,Ma Z Y. Development of Synthesis of Steroid Drugs from Tigogenin in China[J]. Chinese J Pharm,2002,33(9):459-464.
[12]	ZHANG Wenzheng,DAI Liyan,WANG Xiaozhong,et al.Synthesis of 4-[(Tetrahydro-2H-pyran-2-yl)oxy] Phenol[J]. J Chem Eng Chinese Univ,2010,24(1):117-121(in Chinese). 张文征,戴立言,王晓钟,等. 4-[(2-四氢吡喃)氧]苯酚的合成[J]. 高校化学工程学报,2010,24(1):117-121.
[13]	FU Xiaolei,ZHAO Chunhui,ZHANG Yixuan,et al.Synthesis, Characterization and Whitening Activity of Amino Acid-Hydroquinone Conjugates[J]. Chinese J Appl Chem,2015,32(2):158-165(in Chinese). 付晓磊,赵春晖,张翼轩,等. 对苯二酚的氨基酸缀合物的合成、表征及美白活性[J]. 应用化学,2015,32(2):158-165.
[14]	Rok Frlan,Stanislav Gobec,Danijel Kikelj. Synthesis of Ethyl 3-(Hydroxyphenoxy)benzyl Butylphosphonates as Potential Antigen 85C Inhibitors[J]. Tetrahedron,2007,63(43):10698-10708.
[15]	LI Jing,DONG Jinhua,XU Liying. Facile Synthetic Method for 2-Benzyloxyphenol[J]. J Shenyang Pharm Univ,2003,20(2):114-115(in Chinese). 李静,董金华,徐莉英. 2-苄氧基苯酚的简易合成方法[J]. 沈阳药科大学学报,2003,20(2):114-115.