Benzylidene-Directed Glycosylations – Mechanistic Insights from Cryogenic Infrared Spectroscopy DOI Creative Commons
Kevin Pagel, Chun‐Wei Chang, Kim Greis

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

Abstract The stereoselective formation of 1,2-cis glycosidic linkages is challenging. currently most widely used strategy for their installation uses 4,6-O-benzylidene protected building blocks. stereoselectivity this reaction thought to be driven by a covalent intermediate, which reacts via an SN2 mechanism. However, the role cationic SN1-type intermediates in unclear. Here, we elucidate structure glycosyl cations carrying groups using cryogenic infrared ion spectroscopy and computational methods. data reveal that unexpectedly form anhydro cations, correlates well with outcome glycosylations. study highlights how can unravel novel sugar chemistry structural linked reactions solution.

Language: Английский

Advances in glycoside and oligosaccharide synthesis DOI Creative Commons
C. Crawford, Peter H. Seeberger

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(22), P. 7773 - 7801

Published: Jan. 1, 2023

The structural complexity of glycans poses a serious challenge in the chemical synthesis glycosides, oligosaccharides and glycoconjugates. Glycan complexity, determined by composition, connectivity, configuration far exceeds what nature achieves with nucleic acids proteins. Consequently, glycoside ranks among most complex tasks organic synthesis, despite involving only simple type bond-forming reaction. Here, we introduce fundamental principles bond formation summarize recent advances oligosaccharide synthesis.

Language: Английский

Citations

45
Characterization of elusive rhamnosyl dioxanium ions and their application in complex oligosaccharide synthesis DOI Creative Commons
Peter H. Moons,

Floor ter Braak,

Frank F. J. de Kleijne

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 13, 2024

Abstract Attaining complete anomeric control is still one of the biggest challenges in carbohydrate chemistry. Glycosyl cations such as oxocarbenium and dioxanium ions are key intermediates glycosylation reactions. Characterizing these highly-reactive understanding their mechanisms essential to stereoselective synthesis complex carbohydrates. Although C-2 acyl neighbouring-group participation has been well-studied, reactive more remote remain elusive challenging study. Herein, we report a workflow that utilized characterize rhamnosyl 1,3-bridged derived from C-3 p -anisoyl esterified donors. First, use combination quantum-chemical calculations infrared ion spectroscopy determine structure cationic intermediate gas-phase. In addition, establish exchange kinetics highly-reactive, low-abundance species solution-phase using chemical saturation transfer, spectroscopy, correlation heteronuclear single-quantum correlation, multiple-bond nuclear magnetic resonance spectroscopy. Finally, apply bacterial oligosaccharides. This combined approach finding answers fundamental physical-chemical questions application organic provides robust basis for elucidating

Language: Английский

Citations

6
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
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
Neighboring‐Group Participation by C‐2 Acyloxy Groups: Influence of the Nucleophile and Acyl Group on the Stereochemical Outcome of Acetal Substitution Reactions DOI Creative Commons
Y. S. CHUN, Wouter A. Remmerswaal, Jeroen D. C. Codée

et al.

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(57)

Published: July 6, 2023

A single acyloxy group at C-2 can control the outcome of nucleophilic substitution reactions pyran-derived acetals, but extent neighboring-group participation depends on a number factors. We show here that does not necessarily stereochemical acetal with weak nucleophiles. The 1,2-trans selectivity increased increasing reactivity incoming nucleophile. This trend suggests intermediacy both cis-fused dioxolenium ions and oxocarbenium in stereochemistry-determining step. In addition, as electron-donating ability neighboring decreased, preference for products increased. Computational studies how barriers ring-opening reaction transition states to provide change capacity C-2-acyloxy

Language: Английский

Citations

10
Stereoelectronic Effect of Protecting Groups on the Stability of Galactosyl Donor Intermediates DOI Creative Commons
R. W. M. Kwok,

Ryan Rutkoski,

Pavel Nagorny

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 218 - 218

Published: Jan. 7, 2025

Using methods of DFT, we investigated the effect electron withdrawing and donating groups on relative stability tentative glycosyl donor reaction intermediates. The calculation shows that by changing stereoelectronic properties protecting group, can influence dioxolenium type intermediates up to 10 kcal mol−1, increasing nucleophillicity 4-O-Bz intermediate becomes more stable than a triflate–donor pair. We exploited this mechanism design galactosyl donors with custom O2 O4, outcome cyclohexanol. showed no change in product distribution, which suggests neighboring group participation takes precedence over remote due kinetic barriers.

Language: Английский

Citations

0
Neighboring-Group Participation by a Less Electron-Donating, Participating C-2-Ester Ensures Higher 1,2-trans Stereoselectivity in Nucleophilic Substitution Reactions of Furanosyl Acetals DOI Creative Commons
Y. S. CHUN, Wouter A. Remmerswaal, Jeroen D. C. Codée

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 90(4), P. 1585 - 1596

Published: Jan. 15, 2025

Nucleophilic substitution reactions of C-2-acyloxy furanosyl acetals can be highly diastereoselective. We here show that the presence a less electron-donating p-nitrobenzoyloxy group at C-2 acetal use to control 1,2-trans stereoselectivity with higher than analogue more benzoyloxy group, just as what was observed in pyranosyl system. Computational results support reaction manifold involving both open oxocarbenium ions and cis-dioxolenium provide 1,2-cis products. Participation by C-2-(p-nitrobenzoyloxy) forms stabilized ion reacts incoming nucleophile readily The relative stability versus is much system result lower energy penalty for forming cis-fused [5,5]-bicyclic dioxolenium ion.

Language: Английский

Citations

0
The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation DOI Creative Commons
Rituparna Das, Balaram Mukhopadhyay

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 369 - 406

Published: Feb. 17, 2025

Stereoselective glycosylations are one of the most challenging tasks synthetic glycochemists. The protecting building blocks on glycosides contribute significantly in attaining required stereochemistry resulting glycosides. Strategic installation suitable groups C-2 position, vicinal to anomeric carbon, renders neighbouring group participation, whereas distal C-3, C-4, and C-6 positions often claimed exhibit remote participation with carbon. Neighbouring being widely studied help glycochemists design protocols for multistep synthesis complex oligosaccharides turn, standardise process glycosylation towards a particular stereochemical output. While has been quite effective achieving produced glycosides, exhibits comparatively less efficacy complete stereoselectivity reactions. Remote is still highly debated topic scientific community. However, implementing participating role reactions practised achieve better stereocontrol facilitate formation synthetically glycosidic linkages.

Language: Английский

Citations

0
Elucidating reactive sugar-intermediates by mass spectrometry DOI Creative Commons
Chun‐Wei Chang, Dana Wehner, Gurpur Rakesh D. Prabhu

et al.

Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 7, 2025

The stereoselective introduction of glycosidic bonds is one the greatest challenges in carbohydrate chemistry. A key aspect controlling glycan synthesis glycosylation reaction which linkages are formed. outcome governed by a reactive sugar intermediate - glycosyl cation. Glycosyl cations highly unstable and short-lived, making them difficult to study using established analytical tools. However, mass-spectrometry-based techniques perfectly suited unravel structure gas phase. main approach involves isolating intermediate, free from external influences such as solvents promoters. Isolation allows examining their integrating orthogonal spectrometric spectroscopic technologies. In this perspective, recent achievements gas-phase research on highlighted. It provides an overview used probe methods for interpreting spectra. connections between data mechanisms solution explored, given that reactions typically performed solution.

Language: Английский

Citations

0
The Stereochemical Outcome of Galactosylations Is Influenced by Both the Position and Electron-Withdrawing Power of Distal Acyl Protecting Groups DOI

Line Juul-Madsen,

Nikolai Cordua,

R Greve

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

The stereodirecting effect of various distal benzoyl esters on the anomeric selectivity in galactopyranosylations was investigated. It found that O-6 galactosyl donors phenyl thioglycoside type had a negligible influence selectivity. Instead, α-selective galactosylations were observed with 4-O-benzoyl, 3,4-di-O-benzoyl, and 4,6-di-O-benzoyl protected donors, highly electron-withdrawing p-nitrobenzoyl (pNO2Bz) protecting group providing most galactosylations. Furthermore, α-selectivity enhanced by replacing thiophenyl aglycon functionality reactive cyclohexyl functionality. These findings enabled successful synthesis biologically relevant α-d-Gal(1→4)Gal linkage. obtained results do not suggest participation as course for selectivities.

Language: Английский

Citations

0