Synthesis of 2′-paclitaxel 2-deoxy-2-fluoro-glucopyranosyl carbonate for specific targeted delivery to cancer cells
Synthesis of 2′-paclitaxel 2-deoxy-2-fluoro-glucopyranosyl carbonate for specific targeted delivery to cancer cells
复制标题
合成 2-紫杉醇 2-脱氧-2-氟-吡喃葡萄糖基碳酸酯，用于特异性靶向递送至癌细胞
DOI：
10.1016/j.carres.2020.108034
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发表时间：
2020
影响因子：
3.1
通讯作者：
Yan Zhang
中科院分区：
文献类型：
--
作者：
Xin Meng;Xujing Lian;Xiao Li;Qiang Ya;Tingshen Li;Yongmin Zhang;Yang Yang;Yan Zhang
利用紫杉醇的2′-OH与2-氟脱氧葡萄糖的C1-羟基之间的连接基团，合成了一种新型的紫杉醇2-氟脱氧葡萄糖共轭衍生物。在前药的制备中，选择烯丙基碳酸酯作为保护基团，并且在合成结束时使用钯化学有效地一步除去烯丙氧基羰基，以良好的产率得到目标分子。该前药不仅改善了紫杉醇的药物性质，如溶解度和稳定性，而且还表现出对癌细胞的细胞毒性和选择性增强，对正常HUVEC细胞的毒性降低。
A novel 2-fluorodeoxyglucose conjugated derivative of paclitaxel was efficiently synthesized using a linker.between 2′-OH of paclitaxel and C1-hydroxyl group of 2-fluorodeoxyglucose. In preparation of the prodrug, allyl.carbonates were selected as the protective group and the efficient one-step removal of allyloxycarbonyl groups at.the end of the synthesis using palladium chemistry gave the target molecule in good yield. The prodrug not only.improved the pharmaceutical properties of paclitaxel, such as solubility and stability, but also demonstrated.enhanced cytotoxicity and selectivity for cancer cells and less toxicity toward normal HUVEC cells.