H5N1进入抑制剂马铃薯三糖吉托皂苷的合成

Synthesis of gitogenin 3β-O-chacotrioside as H5N1 entry inhibitor

目的设计并合成马铃薯三糖吉托皂苷(Ⅱ),研究先导化合物chlorogenin 3-O-β-chacotrioside(Ⅰ)苷元结构中不同C6-OH位点对目标化合物抑制H5N1假病毒活性的影响。方法采用逐步线性合成的策略,以3α-吉托皂苷类似物为起始原料,依次经酯化、氧化、还原、糖苷化、脱保护基等反应操作制备得到化合物Ⅱ;利用建立在细胞水平的H5N1假病毒活性检测方法测试了其抑制活性。结果目标化合物Ⅱ的总收率为20.9%,其化学结构经NMR、MS确证。结论将化合物Ⅰ结构中的6-羟基薯蓣皂苷元替换成吉托皂苷元可致抗病毒活性下降。

OBJECTIVE To design and synthesize gitogenin 313 - O - chacotrioside （Ⅱ） , and to study the influence of the different site of C6 - OH in the aglycone of the lead compound chlorogenin 313 - O - chacotrioside（Ⅰ ） on the inhibition activity of compound Ⅱagainst H5N1. METHODS Stepwise linear synthetic strategy was adopted, target compound was synthesized successively by ester- ification, oxidation, reduction, glycosylation and the removal of the protective group using 3α -gitogenin derivatives as the starting mate- rial. The inhibitory activity of the target compound Ⅱ against H5N1 influenza was tested at a celluar level by H5N1 pseudovirus activity detection method. RESULTS Target compound Ⅱ was obtained with the yield of 20.9%, and the structures were identified by NMR and MS. CONCLUSION The inhibitory activity against HSN1 influenza virus of the compound I has been decreased when changing the 6 - hydroxy diosgenin aglycone into gitogenin aglvcone.