BACKGROUND Podophyllotoxin is a natural lignan which possesses anticancer and antiviral activities. Etoposide and teniposide are semisynthetic glycoside derivatives of podophyllotoxin and are increasingly used in cancer medicine. OBJECTIVE The present work aimed to design and synthesize a series of 2, 4, 5-trideoxyhexopyranosides derivatives of 4'-demethylepipodophyllotoxin as novel anticancer agents. METHODS A divergent de novo synthesis of 2, 4, 5-trideoxyhexopyranosides derivatives of 4'- demethylepipodophyllotoxin has been established via palladium-catalyzed glycosylation. The abilities of synthesized glycosides to inhibit the growth of A549, HepG2, SH-SY5Y, KB/VCR and HeLa cancer cells were investigated by MTT assay. Flow cytometric analysis of cell cycle with propidium iodide DNA staining was employed to observe the effect of compound 5b on cancer cell cycle. RESULTS Twelve D and L monosaccharide derivatives 5a-5l have been efficiently synthesized in three steps from various pyranone building blocks employing de novo glycosylation strategy. Dmonosaccharide 5b showed the highest cytotoxicity on five cancer cell lines with the IC50 values ranging from 0.9 to 6.7 μM. It caused HepG2 cycle arrest at G2/M phase in a concentrationdependent manner. CONCLUSION The present work leads to the development of novel 2, 4, 5-trideoxyhexopyranosides derivatives of 4'-demethylepipodophyllotoxin. The biological results suggest that the replacement of the glucosyl moiety of etoposide with 2, 4, 5-trideoxyhexopyranosyl is favorable to their cytotoxicity. D-monosaccharide 5b was observed to cause HepG2 cycle arrest at the G2/M phase in a concentration- dependent manner.

中文翻译：

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2, 4, 5-Trideoxyhexopyranosides 4'-去甲基表鬼臼毒素衍生物：从头合成和抗癌活性。

背景技术鬼臼毒素是一种具有抗癌和抗病毒活性的天然木脂素。依托泊苷和替尼泊苷是鬼臼毒素的半合成糖苷衍生物，越来越多地用于癌症医学。目的本工作旨在设计和合成一系列4'-去甲基表鬼臼毒素的2, 4, 5-三氧代吡喃己糖苷衍生物作为新型抗癌药物。方法 已通过钯催化的糖基化建立了 4'-去甲基表鬼臼毒素的 2, 4, 5-三聚氧吡喃糖苷衍生物的不同从头合成。通过MTT法研究了合成的糖苷抑制A549、HepG2、SH-SY5Y、KB/VCR和HeLa癌细胞生长的能力。采用碘化丙啶DNA染色的细胞周期流式细胞术分析来观察化合物5b对癌细胞周期的影响。结果 12 种 D 和 L 单糖衍生物 5a-5l 已采用从头糖基化策略从各种吡喃酮结构单元分三步有效合成。Dmonosaccharide 5b 对五种癌细胞系表现出最高的细胞毒性，IC50 值范围为 0.9 至 6.7 μM。它以浓度依赖性方式导致 HepG2 周期停滞在 G2/M 期。结论 目前的工作导致了 4'-去甲基表鬼臼毒素的新型 2, 4, 5-trideoxy hexopyranosides 衍生物的开发。生物学结果表明，用2, 4, 5-三氧代吡喃己糖基取代依托泊苷的葡糖基部分有利于它们的细胞毒性。