Fries-type Reactions for the C-Glycosylation of Phenols

Santos, Rui; Jesus, Ana Rita; Caio, João M.; Rauter, Amélia P.

doi:10.2174/138527211793797855

Cited by 36 publications

(21 citation statements)

References 51 publications

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“…For instance, Fries-type reactions, which involve a phenolic scaffold and sugar, form a glycoside during an early stage. Afterward, and via intra-molecular arrangement, this leads to C-glycosylated compounds (Dos Santos et al 2011;Dos Santos et al 2013). These types of compounds are supposed to have more affinity with the aqueous phase.…”

Section: Resultsmentioning

confidence: 99%

Acid Liquefaction of Potato (Solanum tuberosum) and Sweet Potato (Ipomoea batatas) Cultivars Peels – Pre-Screening of Antioxidant Activity/Total Phenolic and Sugar Contents

Mateus

Ventura²,

Rego

et al. 2017

BioResources

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In the present study, the liquefaction of both regular and sweet potato peels was conducted to investigate the bio-oil produced, the sugar and total phenolic content, and antioxidant activity. Initially, the bio-oil obtained after liquefaction was partitioned into two different fractions, a hydrophilic fraction and the other consisted of the portion that contained the apolar compounds. Afterward, the samples of the whole bio-oil, aqueous extract, and organic phase of both cultivars were analyzed by attenuated total reflection-Fourier Transform infrared (ATR-FTIR) spectroscopy, hydroxyl number, and acid value. This was done in combination with assessment of the sugar and total phenolic contents and antioxidant activity. The samples demonstrated a considerable content of phenolic moieties in their composition. The antioxidant activity, which was assessed by the 2,2-diphenyl-1-picrylhydrazyl radical method, revealed that the antioxidants of the liquefied products and its extracts were generally better than that of butylated hydroxytoluene. Glucose, sucrose, and maltose were identified and quantified within all of the samples.

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Section: Resultsmentioning

confidence: 99%

Acid Liquefaction of Potato (Solanum tuberosum) and Sweet Potato (Ipomoea batatas) Cultivars Peels – Pre-Screening of Antioxidant Activity/Total Phenolic and Sugar Contents

Mateus

Ventura²,

Rego

et al. 2017

BioResources

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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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“…17–22 The most common approaches focus on (i) nucleophilic addition of an organometallic reagent (e.g., organozinc) 23,24 to anomeric halides catalyzed by Ni, 25–28 Co, Pd, and Fe 29 complexes, (ii) addition of a nucleophile to a lactone followed by reduction of the resultant acetal, and (iii) Friedel‒Crafts-type alkylation of electron-rich arenes or direct phenol O -glycosylation followed by a stereoselective O→C rearrangement. 30,31 In the context of C(sp 2 )−C(sp 2 ) cross-couplings, reactions of glycals in the form of a C1-nucleophile 32 or a C1-electrophile 33–35 have been described. These methods often represent a viable solution to a particular synthetic problem and the key limitations such as the control of anomeric configuration dependent on the identity of the saccharide and the C2 substituents, functional group compatibility of the nucleophilic reagents, and the need for additional manipulations required to establish a proper carbohydrate core prevent their widespread use.…”

Section: Introductionmentioning

confidence: 99%

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides

et al. 2017

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Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd(dba) (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the β-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the β-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.

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Fries-type Reactions for the C-Glycosylation of Phenols

Cited by 36 publications

References 51 publications

Acid Liquefaction of Potato (Solanum tuberosum) and Sweet Potato (Ipomoea batatas) Cultivars Peels – Pre-Screening of Antioxidant Activity/Total Phenolic and Sugar Contents

Acid Liquefaction of Potato (Solanum tuberosum) and Sweet Potato (Ipomoea batatas) Cultivars Peels – Pre-Screening of Antioxidant Activity/Total Phenolic and Sugar Contents

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

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides

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