摘要
通过异亚丙基和苄基的选择性保护和脱保护法,分别方便地合成了6位带有自由羟基的半乳糖和葡萄糖,并进一步选择性地对其进行6位苯甲酰基化修饰从而获得相应糖给体。从6位苯甲酰基化半乳糖和葡萄糖糖给体出发,立体专一性地合成了β-构型的芳香碳糖苷中间体,再经硝酸铈铵(CAN)温和氧化烷氧基苯获得6-O-苯甲酰基苯醌碳糖苷目标化合物,其中4个结构未见文献报道。经1HNMR、13CNMR谱及高分辨质谱测试技术分析确证了目标化合物结构。采用MTT法考察了目标化合物对黑色素肿瘤细胞株A375的体外抑制活性。结果表明,2-(2,3,4-三-O-乙酰基-6-O-苯甲酰基-β-D-吡喃半乳糖)-1,4-苯醌(6)和2-(2,3,4-三-O-乙酰基-6-O-苯甲酰基-β-D-吡喃葡萄糖)-1,4-苯醌(15)显示体外抗肿瘤活性。对此类化合物进一步的结构优化,开发高选择性、高活性的抗肿瘤先导化合物提供了信息。
Galactopyranose and glucopyranose with 6-position hydroxyl were conveniently synthesized by selective protection and deprotection of isopropylidene group and benzyl group respectively. Selective benzoylation on 6-position of galactose and glucose could be achieved from the 6-position hydroxyl compounds and then β-aryl C-glycoside intermediates were obtained with high stereoselectivity by means of introducing the glycosyl donors onto 1,4-dimethoxyl benzene. Under moderate oxidation with CAN （eerie ammonium nitrate） , 6-O- benzoyl C-glycosyl benzoquinones were prepared and for of them have not been reported. The structures of target compounds were confirmed by ^1H NMR, ^13C NMR and HRMS spectroscopy. Anti-tumor activity tests including IC50 by MTT tetrazolium dye assay against human melanoma A375 cell line were carried out. The results show that 6-O-benzoyl C-glycosyl benzoquinones possess moderate anti-tumor activity. This character will make them useful in the structure modification and discovery of some potential antitumor with high selectivity and high activity.
出处
《应用化学》
CAS
CSCD
北大核心
2007年第10期1109-1114,共6页
Chinese Journal of Applied Chemistry
基金
国家自然科学基金(20576034)资助项目
上海市自然科学基金(05ZR14040)资助项目
关键词
O-选择性修饰
苯醌碳糖苷
合成
抗肿瘤生物活性
selective O-modification, C-glycosyl benzoquinones, synthesis, anti-tumor activity
