Department of Chemistry, Boston College, Chestnut Hill, MA, 02467, USA.
Angew Chem Int Ed Engl. 2020 Oct 12;59(42):18435-18441. doi: 10.1002/anie.202007211. Epub 2020 Aug 20.
O-sulfation is an important chemical code widely existing in bioactive molecules, but the scalable and facile synthesis of complex bioactive molecules carrying O-sulfates remains challenging. Reported here is a general approach to O-sulfation by the sulfur(VI) fluoride exchange (SuFEx) reaction between aryl fluorosulfates and silylated hydroxy groups. Efficient sulfate diester formation was achieved through systematic optimization of the electronic properties of aryl fluorosulfates. The versatility of this O-sulfation strategy was demonstrated in the scalable syntheses of a variety of complex molecules carrying sulfate diesters at various positions, including monosaccharides, disaccharides, an amino acid, and a steroid. Selective hydrolytic and hydrogenolytic removal of the aryl masking groups from sulfate diesters yielded the corresponding O-sulfate products in excellent yields. This strategy provides a powerful tool for the synthesis of O-sulfate bioactive compounds.
-O- 磺化是生物活性分子中广泛存在的一种重要化学编码，但具有 -O- 磺酸盐的复杂生物活性分子的规模化和简便合成仍然具有挑战性。本文报道了一种通过芳基氟硫酸酯与硅烷化羟基之间的硫（VI）氟交换（SuFEx）反应进行 -O- 磺化的通用方法。通过系统优化芳基氟硫酸酯的电子性质，实现了高效的硫酸二酯形成。该 -O- 磺化策略的多功能性在各种复杂分子的规模化合成中得到了证明，这些分子在不同位置带有硫酸二酯，包括单糖、二糖、氨基酸和甾体。对硫酸二酯的芳基掩蔽基团进行选择性水解和氢解，可以以优异的收率得到相应的-O- 磺酸盐产物。该策略为 O- 磺酸盐生物活性化合物的合成提供了一种强大的工具。
