Facile Approach to<i>C</i>‐Glucosides by Using a Protecting‐Group‐Free Hiyama Cross‐Coupling Reaction: High‐Yielding Dapagliflozin Synthesis

Vaňková, Karolína; Rahm, Michal; Choutka, Jan; Pohl, Radek; Parkan, Kamil

doi:10.1002/chem.202101052

Cited by 7 publications

(3 citation statements)

References 31 publications

(41 reference statements)

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“…When the silylprotecting groups were changed to benzyl groups, further transformation with DMDO and Superhydride was conducted to afford the desired C-glycosides 11 with highly controlled αconfiguration. 53,54 Collectively, we have demonstrated that our newly developed method could be applied to generate structurally diverse and functionalized C-glycosides rapidly and efficiently.…”

Section: Scalable Synthesis and Late-stage Diversifications To Genera...mentioning

confidence: 86%

C–H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors

et al. 2023

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C-Glycosides are critical motifs embedded in many bioactive natural products. The inert C-glycosides are privileged structures for developing therapeutic agents owing to their high chemical and metabolic stability. Despite the comprehensive strategies and tactics established in the past few decades, highly efficient C-glycoside syntheses via C–C coupling with excellent regio-, chemo-, and stereoselectivity are still needed. Here, we report the efficient Pd-catalyzed glycosylation of C–H bonds promoted by weak coordination with native carboxylic acids without external directing groups to install various glycals to the structurally diverse aglycon parts. Mechanistic evidence points to the participation of a glycal radical donor in the C–H coupling reaction. The method has been applied to a wide range of substrates (over 60 examples), including many marketed drug molecules. Natural product- or drug-like scaffolds with compelling bioactivities have been constructed using a late-stage diversification strategy. Remarkably, a new potent sodium-glucose cotransporter-2 inhibitor with antidiabetic potential has been discovered, and the pharmacokinetic/pharmacodynamic profiles of drug molecules have been changed using our C–H glycosylation approach. The method developed here provides a powerful tool for efficiently synthesizing C-glycosides to facilitate drug discovery.

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Section: Scalable Synthesis and Late-stage Diversifications To Genera...mentioning

confidence: 86%

C–H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors

et al. 2023

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“…Access to C-glycosides, which is an inhibitor of sodium–glucose cotransporter-2, via protecting a group-free Hiyama coupling reaction, has been developed. This strategy has been reported to synthesize pharmaceutically significant dapagliflozin compound that is useful to cure type 2 diabetes mellitus [ 33 ]. Hiyama cross-coupling offers 2-functionalized indoles formation by means of rhodium metal catalyst [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Transition Metal Catalyzed Hiyama Cross-Coupling: Recent Methodology Developments and Synthetic Applications

et al. 2022

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Hiyama cross-coupling is a versatile reaction in synthetic organic chemistry for the construction of carbon–carbon bonds. It involves the coupling of organosilicons with organic halides using transition metal catalysts in good yields and high enantioselectivities. In recent years, hectic progress has been made by researchers toward the synthesis of diversified natural products and pharmaceutical drugs using the Hiyama coupling reaction. This review emphasizes the recent synthetic developments and applications of Hiyama cross-coupling.

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“…1A). 11 These compounds function as SGLT-2 inhibitors and are employed in the treatment of type-2 diabetes, underscoring the significant strides made in harnessing C -aryl glycosides for pharmaceutical purposes. 12…”

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confidence: 99%

Pd-catalyzed stereoselective synthesis of chromone C-glycosides

Sharma,

Tiwari,

Hussain

2024

Chem. Commun.

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Facile Approach toC‐Glucosides by Using a Protecting‐Group‐Free Hiyama Cross‐Coupling Reaction: High‐Yielding Dapagliflozin Synthesis

Cited by 7 publications

References 31 publications

C–H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors

C–H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors

Transition Metal Catalyzed Hiyama Cross-Coupling: Recent Methodology Developments and Synthetic Applications

Pd-catalyzed stereoselective synthesis of chromone C-glycosides

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