Facile Approach to <i>C</i>‐Glucosides by Using a Protecting‐Group‐Free Hiyama Cross‐Coupling Reaction: High‐Yielding Dapagliflozin Synthesis
Karolína Vaňková, Michal Rahm, Jan Choutka, Radek Pohl, Kamil Parkan
Abstract
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.
Topics & Concepts
DapagliflozinArylGlucalChemistryProtecting groupCoupling reactionCombinatorial chemistryHalideStereochemistryOrganic chemistryCatalysisDiabetes mellitusType 2 Diabetes MellitusAlkylEndocrinologyMedicineCarbohydrate Chemistry and SynthesisSynthesis of Organic CompoundsPlant-derived Lignans Synthesis and Bioactivity