Cobalt-Catalyzed versus Base-Promoted Skeletal- and Stereodivergent Synthesis of Bicyclic α-C-, β-O-, and α-O-Glycosides DOI
Zhen Cao, Yujie Niu, Xingxing Jiang

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 9, 2025

A stereodivergent synthesis of bicyclic α-C-, β-O-, and α-O-glycosides is achieved with nonprecious Co(dpm)3, K2CO3, DBU, respectively. Cobalt-catalyzed decarboxylative allylation 2,3-unsaturated 4-keto glycosyl carbonates 1,3-diketones delivers α-C-glycosides in good yields exclusive chemo- regiocontrol excellent diastereoselectivity (>20:1 dr). K2CO3 enables β-O-glycosides via a cascaded intermolecular Michael addition/SN2-like cyclization, whereas DBU promotes further C5 epimerization to give α-O-glycosides. Mechanistic studies (deuterium labeling intermediate capturing) validate the pathways. Gram-scale late-stage functionalization pharmaceuticals demonstrate practicality.

Language: Английский

Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century DOI
Yashapal Singh, Scott A. Geringer, Alexei V. Demchenko

et al.

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(13), P. 11701 - 11758

Published: June 8, 2022

Advances in synthetic carbohydrate chemistry have dramatically improved access to common glycans. However, many novel methods still fail adequately address challenges associated with chemical glycosylation and glycan synthesis. Since a challenge of has remained, scientists been frequently returning the traditional glycosyl donors. This review is dedicated halides that played crucial roles shaping field glycosciences continue pave way toward our understanding glycosylation.

Language: Английский

Citations

67
Anomeric Triflates versus Dioxanium Ions: Different Product-Forming Intermediates from 3-Acyl Benzylidene Mannosyl and Glucosyl Donors DOI Creative Commons
Wouter A. Remmerswaal, Hidde Elferink, Kas J. Houthuijs

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(3), P. 1618 - 1625

Published: Jan. 18, 2024

Minimal structural differences in the structure of glycosyl donors can have a tremendous impact on their reactivity and stereochemical outcome glycosylation reactions. Here, we used combination systematic reactions, characterization potential reactive intermediates, in-depth computational studies to study disparate behavior systems involving benzylidene glucosyl mannosyl donors. While these been studied extensively, no satisfactory explanations are available for observed between 3-

Language: Английский

Citations

11
The Stereoselectivity of Neighboring Group-Directed Glycosylation Is Concentration-Dependent DOI Creative Commons
Pallabita Basu, David Crich

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

The formation of 1,2-trans-glycosides taking advantage neighboring group participation by stereodirecting esters at the 2-position glycosyl donors is widely held to be a robust and reliable protocol. Examples abound, however, cases in which less-than-perfect selectivity obtained, causing practitioners survey different or resort alternative strategies quest for optimal selectivities yields. Consideration mechanism particular competing process SN2-like glycosylation with activated covalent leads hypothesis that imperfect selectivity, more careful attention reaction concentration stoichiometry may beneficial. Three case studies are presented demonstrate dependence group-directed reactions targeting both 1,2-trans-equatorial 1,2-trans-axial glycosides. Higher concentrations, whether achieved through increased acceptor:donor fixed stoichiometry, mostly lead erosion 1,2-trans-selectivity as becomes increasingly important. These observations underline importance rational, mechanism-based approach general importantly suggest simple enhancing displaying 1,2-trans-selectivity, namely, moving regime.

Language: Английский

Citations

1
Towards a Systematic Understanding of the Influence of Temperature on Glycosylation Reactions DOI
Owen T. Tuck, Eric T. Sletten, José Danglad‐Flores

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(15)

Published: Jan. 15, 2022

Glycosidic bond formation is a continual challenge for practitioners. Aiming to enhance the reproducibility and efficiency of oligosaccharide synthesis, we studied relationship between glycosyl donor activation reaction temperature. A novel semi-automated assay revealed diverse responses members panel thioglycosides at various temperatures. The patterns protecting groups thiol aglycon combine cause remarkable differences in temperature sensitivity among building blocks. We introduce concept capture experimental insights, reasoning that glycosylations performed below this reference evade deleterious side reactions. Activation temperatures enable simplified treatment facilitate optimization usage. Isothermal glycosylation halved equivalents block required comparison standard "ramp" regime used solution- solid-phase synthesis to-date.

Language: Английский

Citations

31
Mapping the effect of configuration and protecting group pattern on glycosyl acceptor reactivity DOI Creative Commons
Jacob M. A. van Hengst,

Rik J. C. Hellemons,

Wouter A. Remmerswaal

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(6), P. 1532 - 1542

Published: Jan. 1, 2023

The reactivity of the acceptor alcohol can have a tremendous influence on outcome glycosylation reaction, both in terms yield and stereoselectivity. Through systematic survey 67 alcohols reactions with two glucosyl donors we here reveal how carbohydrate depends its configuration substitution pattern. study shows functional groups flanking show that nature relative orientation play an essential role. empiric guidelines revealed will aid rational optimization be important tool assembly oligosaccharides.

Language: Английский

Citations

18
Detection and Characterization of Rapidly Equilibrating Glycosylation Reaction Intermediates Using Exchange NMR DOI Creative Commons
Frank F. J. de Kleijne,

Floor ter Braak,

Dimitrios Piperoudis

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(48), P. 26190 - 26201

Published: Nov. 27, 2023

The stereoselective introduction of glycosidic bonds (glycosylation) is one the main challenges in chemical synthesis carbohydrates. Glycosylation reaction mechanisms are difficult to control because, many cases, exact reactive species driving product formation cannot be detected and outcome explained by primary intermediate observed. In these reactions expected take place via other low-abundance intermediates that rapid equilibrium with a Curtin-Hammett scenario. Despite this principle being well-known organic synthesis, mechanistic studies investigating model glycosylation complicated challenge detecting extremely short-lived responsible for formation. Herein, we report utilization between stable, readily observed α-glycosyl triflate order infer structure former employing exchange NMR. Using technique, enabled detection such as β-glycosyl triflates glycosyl dioxanium ions. This demonstrates power NMR unravel aim build catalog kinetic parameters, allowing understanding eventual prediction reactions.

Language: Английский

Citations

17
The Influence of the Electron Density in Acyl Protecting Groups on the Selectivity of Galactose Formation DOI Creative Commons
Kim Greis,

Sabrina Leichnitz,

Carla Kirschbaum

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(44), P. 20258 - 20266

Published: Oct. 27, 2022

The stereoselective formation of 1,2-cis-glycosidic bonds is a major bottleneck in the synthesis carbohydrates. We here investigate how electron density acyl protecting groups influences stereoselectivity by fine-tuning efficiency remote participation. Electron-rich C4-pivaloylated galactose building blocks show an unprecedented α-selectivity. trifluoroacetylated counterpart with electron-withdrawing groups, on other hand, exhibits lower selectivity. Cryogenic infrared spectroscopy helium nanodroplets and functional theory calculations revealed existence dioxolenium-type intermediates for this reaction, which suggests that participation pivaloyl group origin high α-selectivity pivaloylated blocks. According to these findings, α-selective block glycosynthesis developed based rational considerations subsequently employed automated glycan assembly exhibiting complete stereoselectivity. Based obtained selectivities glycosylation reactions results from theory, we suggest mechanism could proceed.

Language: Английский

Citations

24
Parametric Analysis of Donor Activation for Glycosylation Reactions DOI Creative Commons
Mei‐Huei Lin,

Yan-Ting Kuo,

José Danglad‐Flores

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(30)

Published: March 28, 2024

Abstract The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. outcome a is contingent upon several environmental factors, such as temperature, acidity, the presence residual moisture, well steric, electronic, conformational aspects reactants. Each proceeds rapidly with high yield within rather narrow temperature range. For better control over glycosylations to ensure fast reliable reactions, systematic analysis 18 glycosyl donors revealed effect reagent concentration, water content, protecting groups, structure activation temperature. With these insights, we parametrize first step reaction be executed reliably efficiently.

Language: Английский

Citations

5
Phenanthroline Catalysis in Stereoselective 1,2-cis Glycosylations DOI
Jiayi Li, Hien M. Nguyen

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(24), P. 3738 - 3751

Published: Nov. 30, 2022

ConspectusThe National Research Council's report in 2012 recognized glycosidic bond forming (glycosylation) reactions as critical due to the central importance of carbohydrates glycosciences. This emphasized need for development reproducible and broadly applicable glycosylation technologies facilitate stereoselective synthesis biomedically relevant glycan libraries tool research applications by nonspecialists. In response this with NIH Common Fund support, publications new catalytic diastereoselective protocols, some broad generality under mild conditions, have been recently reported our group others. These recent discoveries also advanced understanding reaction mechanism involving coupling a sugar electrophile bearing leaving at its C1-anomeric center an alcohol nucleophile. can lead mixture two stereoisomers that differ configuration anomeric center.In group, we discovered readily available phenanthroline, rigid planar organic compound fused pyridine rings, could be utilized nucleophilic catalyst promote highly nucleophile bromide electrophile. The phenanthroline catalysis process allows access myriad high yielding 1,2-cis pyranosides furanosides. catalyst-controlled approach has applied potential vaccine adjuvant α-glucan octasaccharide. For pyranosyl electrophiles, extensive mechanistic investigation illustrated phenanthrolinium ion intermediates, 4C1 chair-liked equatorial-conformer B2,5 boat-like axial-conformer, are formed ratio 2:1 (equatorial/axial). To obtain levels axial-1,2-cis selectivity, Curtin–Hammett scenario was proposed wherein interconversion axial-conformer is more rapid than addition. Hydroxyl attack takes place from axial-face reactive chairlike equatorial intermediate afford glycoside product. system number furanosyl electrophiles provide challenging substitution products good yield diastereoselectivity. NMR experiments density-functional theory (DFT) calculations support associative which rate-determining step invertive displacement faster reacting Overall, work stands underdeveloped intersection operationally simple catalysis, stereocontrolled formation, each represents important theme preparation biologically oligosaccharides glycopeptides human health medicine.

Language: Английский

Citations

21
Unraveling the promoter effect and the roles of counterion exchange in glycosylation reaction DOI Creative Commons
Chun‐Wei Chang, Mei‐Huei Lin, Tsun-Yi Chiang

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(42)

Published: Oct. 18, 2023

The stereoselectivity of glycosidic bond formation continues to pose a noteworthy hurdle in synthesizing carbohydrates, primarily due the simultaneous occurrence S

Language: Английский

Citations

13