Trauner Florian, Boutet Bilel, Pilz Fabian, Weber Verena, Didier Dorian
Technische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Peter-Grünberg-Straße 4, 64287, Darmstadt, Germany.
Ludwig-Maximillians Universität, Department Chemie, Butenandtstraße 5, 81377, Munich, Germany.
Commun Chem. 2024 Dec 21;7(1):306. doi: 10.1038/s42004-024-01339-4.
C-glycosides are significant in medicinal chemistry due to their resistance to enzymatic hydrolysis, making them more stable and bioavailable compared to O-glycosides. Their unique structure also offers potential for developing drugs with improved therapeutic properties, particularly in treating diseases like diabetes and cancer. The main challenge in synthesizing C-glycosides lies in forming the carbon-carbon bond between the sugar and aglycone efficiently, while controlling the stereochemistry and minimizing side reactions. Starting from glycal derivatives, the Zweifel olefination presents an elegant opportunity to access C-glycosides in a selective manner. α-Lithiation of D-glucal, L-rhamnal, D-xylal and L-arabinal scaffolds was employed as a starting point in the synthesis of corresponding unsaturated aryl-, heteroaryl- and alkenyl-C-glycosides. This provides a straightforward strategy towards pharmacorelevant gliflozins and other unreported rhamnal- and xylal-analogs.
C-糖苷在药物化学中具有重要意义，因为它们对酶促水解具有抗性，与O-糖苷相比，使其更稳定且生物利用度更高。它们独特的结构还为开发具有改善治疗特性的药物提供了潜力，特别是在治疗糖尿病和癌症等疾病方面。合成C-糖苷的主要挑战在于有效地在糖和苷元之间形成碳-碳键，同时控制立体化学并使副反应最小化。从糖烯衍生物开始，Zweifel烯化反应为以选择性方式获得C-糖苷提供了一个很好的机会。D-葡萄糖烯、L-鼠李糖烯、D-木糖烯和L-阿拉伯糖烯支架的α-锂化被用作合成相应的不饱和芳基、杂芳基和烯基-C-糖苷的起点。这为制备与药效团相关的格列净和其他未报道的鼠李糖烯和木糖烯类似物提供了一种直接的策略。
