Fakultät für Chemie und Pharmazie, Universität Hamburg, Bundesstraße 45, 20146, Hamburg, Germany.
Fachbereich Chemie, Institut für Pharmazie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Chemistry. 2022 Dec 20;28(71):e202202619. doi: 10.1002/chem.202202619. Epub 2022 Oct 26.
Due to their high stability towards enzymatic hydrolysis C-acyl glycosidic compounds are useful synthetic intermediates for potential candidates in drug discovery. Syntheses for C-acyl mannosides have remained scarce and usually employ donors obtained from lengthy syntheses. Furthermore, syntheses of unprotected C-acyl mannosides have not been reported so far, due to the incapability of the C-acyl mannoside motif with deprotection conditions for protective groups commonly used in carbohydrate chemistry. Herein, we report an efficient and highly α-selective four-step one-pot method for the synthesis of C-acyl α-d-manno-, l-rhamno- and d-lyxopyranosides from easily accessible persilylated monosaccharides and dithianes requiring only trace amounts of a copper source as catalyst and explain the crucial role of the catalyst by mechanistic studies. Furthermore, the C-acyl α-glycosides were easily isomerized to give rapid access to their β-anomers.
由于 C-酰基糖苷化合物对酶解具有很高的稳定性，因此它们是药物发现中潜在候选物的有用合成中间体。C-酰基甘露糖苷的合成仍然很少见，通常使用来自冗长合成的供体。此外，由于无法使用碳水化合物化学中常用的保护基团的脱保护条件来保护 C-酰基甘露糖苷基元，因此到目前为止还没有报道未保护的 C-酰基甘露糖苷的合成。在此，我们报告了一种从易于获得的硅烷化单糖和二噻烷出发高效且高度α选择性的四步一锅法合成 C-酰基α-D-甘露糖苷，L-鼠李糖苷和 D-来苏糖苷的方法，该方法仅需痕量的铜源作为催化剂，通过机理研究解释了催化剂的关键作用。此外，C-酰基α-糖苷很容易异构化为其β-异构体，从而快速获得。
