Umpolung Reactivity in the Stereoselective Synthesis of S‐Linked 2‐Deoxyglycosides

Baryal, Kedar N.; Zhu, Dong; Li, Xiaohua; Zhu, Jianglong

doi:10.1002/ange.201301682

Cited by 18 publications

(6 citation statements)

References 75 publications

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“…Zhu and co-workers379 have developed a very elegant approach for the stereoselective synthesis of S-linked 2deoxyglycosides that includes both the α-linked and the morechallenging β-linked counterparts. The method relies on the sulfenylation of 2-deoxyglycosyl lithium species 382 and 383, which are stereochemically defined, with disulfide glycoside acceptors such as 384 to yield the desired products (385 and 386) with excellent stereocontrol (Scheme 103).…”

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confidence: 99%

Methods for 2-Deoxyglycoside Synthesis

2018

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Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

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Methods for 2-Deoxyglycoside Synthesis

2018

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“…10 Anomeric anions undergo stereoretentive addition to a range of electrophiles, 11 and have found use in the preparation of glycosylsulfides. 12 Thus, we recognized that these anomeric anions might form the basis for a method to access both αand β-2-deoxyglycosides from a single starting material. As a collateral benefit, the configuration of the starting phenyl thioglycoside is inconsequential because the reductive lithiation proceeds by stepwise electron transfer.…”

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Programmable Synthesis of 2-Deoxyglycosides

2019

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Control of glycoside bond stereochemistry is the central challenge in the synthesis of oligosaccharides. 2-Deoxyglycosides, which lack a C2 substituent to guide stereoselectivity, are among the most difficult classes of glycoside bond constructions. Here we present a method to synthesize 2-deoxysaccharides with specified glycoside bond stereochemistry using a nucleophilic carbohydrate residue and the synthetic equivalent of an alcohol electrophile.Because the configuration of the nucleophile can be precisely controlled, both αand βglycosides can be synthesized from the same starting material in nearly all cases examined.Stereoselectivities in these reactions are often greater than 50:1 and yields typically exceed 70%.This strategy is amenable to the stereocontrolled syntheses of trisaccharide diastereomers, and a tetrasaccharide. Our method offers a fundamentally new approach to O-glycoside synthesis to enable downstream biochemical and natural product applications.

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“…4,23 Thus, in order to access both anomers of thioglycosides, an alternative synthetic platform would be necessary, and a complementary approach capitalizes on reversal of polarity at the anomeric carbon. Organolithium 24 and Grignard 25 their incompatibility with various functional groups commonly found in peptides and proteins. 26,27 The formation of a C(sp 2 )−S bond in small molecules and proteins has been accomplished with various aryl nucleophiles such as boronic acids, 28−31 organopalladium, 32 and organogold 33 reagents.…”

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confidence: 99%

Stereoretentive C(sp³)–S Cross-Coupling

et al. 2018

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We report a stereoretentive cross-coupling reaction of configurationally stable nucleophiles with disulfide and N-sulfenylsuccinimide donors promoted by Cu(I). We demonstrate the utility of this method in the synthesis of thioglycosides derived from simple alkyl and aryl thiols, thioglycosides, and in the glycodiversification of cysteine residues in peptides. These reactions operate well with carbohydrate substrates containing common protective groups and reagents with free hydroxyl and secondary amide functionalities under standardized conditions. Competition experiments in combination with computational DFT studies established that the putative anomeric intermediate is an organocopper species that is configurationally stable and resistant to epimerization due to its short lifetime. The subsequent reductive elimination from the Cu(III) intermediate is rapid and stereoretentive. Taken together, the glycosyl cross-coupling is ideally suited for late stage glycodiversification and bioconjugation under highly controlled installation of the aliphatic carbon–sulfur bonds.

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Umpolung Reactivity in the Stereoselective Synthesis of S‐Linked 2‐Deoxyglycosides

Cited by 18 publications

References 75 publications

Methods for 2-Deoxyglycoside Synthesis

Methods for 2-Deoxyglycoside Synthesis

Programmable Synthesis of 2-Deoxyglycosides

Stereoretentive C(sp³)–S Cross-Coupling

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Umpolung Reactivity in the Stereoselective Synthesis of S‐Linked 2‐Deoxyglycosides

Cited by 18 publications

References 75 publications

Methods for 2-Deoxyglycoside Synthesis

Methods for 2-Deoxyglycoside Synthesis

Programmable Synthesis of 2-Deoxyglycosides

Stereoretentive C(sp3)–S Cross-Coupling

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Stereoretentive C(sp³)–S Cross-Coupling