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

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
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
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
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
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
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
Competing C‐4 and C‐5‐Acyl Stabilization of Uronic Acid Glycosyl Cations DOI
Hidde Elferink, Wouter A. Remmerswaal, Kas J. Houthuijs

et al.

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(63)

Published: Aug. 12, 2022

Uronic acids are carbohydrates carrying a terminal carboxylic acid and have unique reactivity in stereoselective glycosylation reactions. Herein, the competing intramolecular stabilization of uronic cations by C-5 or C-4 acetyl group was studied with infrared ion spectroscopy (IRIS). IRIS reveals that mixture bridged ions is formed, which driven towards C-1,C-5 dioxolanium when C-5,C-2-relationship cis, formation C-1,C-4 dioxepanium this relation trans. Isomer-population analysis interconversion barrier computations show two structures not dynamic equilibrium their ratio parallels density functional theory computed stability structures. These studies reveal how intrinsic interplay different groups influences regioisomeric products.

Language: Английский

Citations

16
Mechanistic insight into benzylidene-directed glycosylation reactions using cryogenic infrared spectroscopy DOI Creative Commons
Chun‐Wei Chang, Kim Greis, Gurpur Rakesh D. Prabhu

et al.

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(11), P. 1377 - 1384

Published: July 26, 2024

The stereoselective formation of 1,2-

Language: Английский

Citations

3
Investigation of Neighboring Group Participation in 3,4‐Diacetylated Glycosyl Donors in the Gas Phase DOI Creative Commons

Floor ter Braak,

Kas J. Houthuijs, Hidde Elferink

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each linkage has one two possible stereo‐chemical geometries, α/β or 1,2‐ cis / trans . An established approach to install bonds neighboring group participation (NGP), mediated by a 2‐ O ‐acyl group. Extension this intramolecular stabilization nucleophilic groups located at more remote positions also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy characterize molecular ions monoacetylated sugar donors and showed how strength stabilizing effect depends on position participating ester glycosyl donor ring as well its relative stereochemistry. In work, investigated carrying acyl groups. Using isotope labelling isomer population analysis were able resolving spectra isomeric mixtures establish contribution individual species. We conclude that 3,4‐diacetyl mannosyl exclusively form dioxanium result C‐3 stabilization. contrast, glucosyl galactosyl cations C‐4 products. Hence, combination labeling allows for study increasingly complex cations.

Language: Английский

Citations

2