Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Molecules. 2018 Jun 15;23(6):1457. doi: 10.3390/molecules23061457.
Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a -dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts.
卤素在规范核苷的各个位置的取代已经产生了许多具有生物活性的结构变体。在此，介绍了两种带有 -二氯基团的糖修饰核苷的独特系列的合成。该合成方案需要将五氯化磷受控添加到适当保护的 2′-或 3′-酮脱氧核苷中间体作为关键步骤，从而促进此类官能化分子的快速构建。在相同的反应条件下，观察到 2′,2′-二氯-2′,3′-二脱氧核苷的形成具有最高的化学选择性，而在 3′,3′-二氯类似物的情况下则发生竞争的 2′,3′-消除过程。
