Synthesis of 2′-paclitaxel 2-deoxy-2-fluoro-glucopyranosyl carbonate for specific targeted delivery to cancer cells

Abstract

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.