Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin, 300457, PR China.
Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin, 300457, PR China.
Carbohydr Res. 2020 Jul;493:108034. doi: 10.1016/j.carres.2020.108034. Epub 2020 May 25.
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.
一种新型的紫杉醇 2-氟脱氧葡萄糖缀合物衍生物通过紫杉醇 2'-OH 与 2-氟脱氧葡萄糖 C1-羟基之间的连接子有效地合成。在制备前药时，选择碳酸烯丙酯作为保护基团，并且在合成结束时使用钯化学有效地一步去除烯丙氧基羰基基团，以良好的收率得到目标分子。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增强的细胞毒性和选择性，以及对正常 HUVEC 细胞的较低毒性。
