A Mitsunobu route to C-glycosides

Pasetto, Paolo; Walczak, Matthew C.

doi:10.1016/j.tet.2009.08.024

Cited by 17 publications

(4 citation statements)

References 52 publications

(20 reference statements)

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“…We also describe the first and successful use of triethylsilane and palladium on carbon for the selective alkene hydrogenation of the reported chalcones, in the presence of the carbonyl group. Whereas C -glucosylation of small phenols has been quite well investigated, − we describe here a new procedure for the C -glucosylation of unprotected dihydrochalcones that uses trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a catalyst. The compounds were assessed for their ability to inhibit glucose uptake by human SGLT1 and SGLT2 in vitro using HEK293 cells stably expressing one or the other of the two proteins and for their impact on cell viability using an assay of metabolic capacity and on GLUT-based glucose transport.…”

Section: Introductionmentioning

confidence: 99%

Targeting Type 2 Diabetes withC-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation

et al. 2017

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Inhibiting glucose reabsorption by sodium glucose co-transporter proteins (SGLTs) in the kidneys is a relatively new strategy for treating type 2 diabetes. Selective inhibition of SGLT2 over SGLT1 is critical for minimizing adverse side effects associated with SGLT1 inhibition. A library of C-glucosyl dihydrochalcones and their dihydrochalcone and chalcone precursors was synthesized and tested as SGLT1/SGLT2 inhibitors using a cell-based fluorescence assay of glucose uptake. The most potent inhibitors of SGLT2 (IC = 9-23 nM) were considerably weaker inhibitors of SGLT1 (IC = 10-19 μM). They showed no effect on the sodium independent GLUT family of glucose transporters, and the most potent ones were not acutely toxic to cultured cells. The interaction of a C-glucosyl dihydrochalcone with a POPC membrane was modeled computationally, providing evidence that it is not a pan-assay interference compound. These results point toward the discovery of structures that are potent and highly selective inhibitors of SGLT2.

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Section: Introductionmentioning

confidence: 99%

Targeting Type 2 Diabetes withC-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation

et al. 2017

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“…Lewis acid catalyzed glycosylation reactions with carbon nucleophiles typically favour the formation of α‐isomers, which require additional steps to be epimerized to the β‐anomers . The stereochemical outcome and efficiency of C‐glycoside synthesis using other methods, including Knoevenagel condensation, Mitsunobu reaction, and a Horner–Wadsworth–Emmons olefination/Michael addition cascade of unprotected/peracylated sugars, are highly dependent on substrates and reaction conditions (Scheme A). For instance, while the condensation of glucose with acetylacetone proceeds with excellent yield, similar reactions with aryl β‐diketones are much lower yielding .…”

Section: Methodsmentioning

confidence: 99%

Versatile Glycosyl Sulfonates in β‐Selective C‐Glycosylation

Ling

Bennett

2020

Angew Chem Int Ed

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C‐Glycosides are both a common motif in many bioactive natural products and important glycoside mimetics. We demonstrate that activating a hemiacetal with a sulfonyl chloride, followed by treating the resultant glycosyl sulfonate with an enolate results in the stereospecific construction of β‐linked C‐glycosides. This reaction tolerates a range of acceptors and donors, including disaccharides. The resulting products can be readily derivatized into C‐glycoside analogues of β‐glycoconjugates, including C‐disaccharide mimetics.

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“…Remarkably, reaction of unprotected sugar lactols with C-nucleophiles could also afford C-glycosides in a simple and direct manner. 446 Treatment of lactol 547 with Wittig reagent PPh 3 CHCO 2 Et gave a mixture of C-glycoside 548 in 85% yield, whereas exposure of 5,6-ene-6-nitro-D-glucofuranose 549 to PPh 3 CHCO 2 Et resulted in the formation of α-C-vinyl glycoside 550 in 75% yield through Wittig olefination and subsequent oxy-Michael addition (Scheme 91). 447,448 Horner−Wadsworth−Emmons olefination of diisopropylidene mannofuranose 551 with glucose-derived phosphonate 552 followed by intramolecular oxy-Michael addition afforded sulfone 553 in 85% yield (α/β = 1:1).…”

Section: C-glycosylation With Sugar Lactolsmentioning

confidence: 99%

Recent Advances in the Chemical Synthesis of C-Glycosides

2017

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Advances in the chemical synthesis of C-pyranosides/furanosides are summarized, covering the literature from 2000 to 2016. The majority of the methods take advantage of the construction of the glycosidic C-C bond. These C-glycosylation methods are categorized herein in terms of the glycosyl donor precursors, which are commonly used in O-glycoside synthesis and are easily accessible to nonspecialists. They include glycosyl halides, glycals, sugar acetates, sugar lactols, sugar lactones, 1,2-anhydro sugars, thioglycosides/sulfoxides/sulfones, selenoglycosides/telluroglycosides, methyl glycosides, and glycosyl imidates/phosphates. Mechanistically, C-glycosylation reactions can involve glycosyl electrophilic/cationic species, anionic species, radical species, or transition-metal complexes, which are discussed as subcategories under each type of sugar precursor. Moreover, intramolecular rearrangements, such as the Claisen rearrangement, Ramberg-Bäcklund rearrangement, and 1,2-Wittig rearrangement, which usually involve concerted pathways, constitute another category of C-glycosylations. An alternative to the C-glycosylations is the formation of pyranoside/furanoside rings after construction of the predetermined glycosidic C-C bonds, which might involve cyclization of acyclic precursors or D-A cycloadditions. Throughout, the stereoselectivity in the formation of the resultant C-glycosidic linkages is highlighted.

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A Mitsunobu route to C-glycosides

Cited by 17 publications

References 52 publications

Targeting Type 2 Diabetes withC-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation

Targeting Type 2 Diabetes withC-Glucosyl Dihydrochalcones as Selective Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors: Synthesis and Biological Evaluation

Versatile Glycosyl Sulfonates in β‐Selective C‐Glycosylation

Recent Advances in the Chemical Synthesis of C-Glycosides

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