Chemistry Department, New York University, 100 Washington Square East, New York, NY, 10003, USA.
Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9433-9438. doi: 10.1002/anie.202014991. Epub 2021 Mar 10.
C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. C-aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C-aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional-group compatibility, and practicality. Challenges remain in the synthesis of C-aryl nucleosides and 2-deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross-coupling method to prepare C-aryl and heteroaryl glycosides, including nucleosides and 2-deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C-O bond homolysis. This strategy represents a new means to activate alcohols as a cross-coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.
C-芳基糖苷化合物相对于 O-和 N-糖苷类似物具有更好的体内稳定性。C-芳基糖苷被广泛研究作为药物候选物，并应用于化学生物学研究。以前，C-芳基糖苷是通过内酯、糖醛、糖苷锡烷和卤化物等方法衍生而来，这些方法在范围、官能团兼容性和实用性方面存在各种限制。从易于获得的碳水化合物前体合成 C-芳基核苷和 2-脱氧糖仍然存在挑战。在此，我们报告了一种交叉偶联方法，可从糖苷酯和溴代芳烃制备 C-芳基和杂芳基糖苷，包括核苷和 2-脱氧糖。碳水化合物底物的活化利用二氢吡啶 (DHP) 作为活化基团，然后通过 C-O 键均裂进行脱羧反应，通过 C-O 键均裂生成糖苷基自由基。该策略代表了一种将醇作为交叉偶联试剂的新方法。糖苷酯的方便制备及其稳定性体现了该方法在药物化学中的潜在应用。
