Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 166 28, Prague 6, Czech Republic.
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Gilead Sciences & IOCB Research Centre, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
Chemistry. 2021 Jul 21;27(41):10583-10588. doi: 10.1002/chem.202101052. Epub 2021 Jun 21.
Access to unprotected (hetero)aryl pseudo-C-glucosides via a mild Pd-catalysed Hiyama cross-coupling reaction of protecting-group-free 1-diisopropylsilyl-d-glucal with various (hetero)aryl halides has been developed. In addition, selected unprotected pseudo-C-glucosides were stereoselectively converted into the corresponding α- and β-C-glucosides, as well as 2-deoxy-β-C-glucosides. This methodology was applied to the efficient and high-yielding synthesis of dapagliflozin, a medicament used to treat type 2 diabetes mellitus. Finally, the versatility of our methodology was proved by the synthesis of other analogues of dapagliflozin.
通过温和的 Pd 催化保护基游离 1-二异丙基硅基-d-葡萄糖醛与各种（杂）芳基卤化物的 Hiyama 交叉偶联反应，可以获得未保护的（杂）芳基伪-C-葡萄糖苷。此外，选择的未保护的伪-C-葡萄糖苷可以立体选择性地转化为相应的α-C-和β-C-葡萄糖苷，以及 2-脱氧-β-C-葡萄糖苷。该方法已成功应用于治疗 2 型糖尿病的药物达格列净的高效高产合成。最后，通过合成达格列净的其他类似物证明了我们方法的多功能性。
