Stereodirecting Effect of Esters at the 4-Position of Galacto- and Glucopyranosyl Donors: Effect of 4-C-Methylation on Side-Chain Conformation and Donor Reactivity, and Influence of Concentration and Stoichiometry on Distal Group Participation DOI Creative Commons
Ande Chennaiah, David Crich

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(19), P. 13883 - 13893

Published: Sept. 7, 2023

When generated in a mass spectrometer bridged bicyclic 1,3-dioxenium ions derived from 4-O-acylgalactopyranosyl, donors can be observed by infrared spectroscopy at cryogenic temperatures, but they are not seen the solution phase contrast to fused 1,3-dioxalenium of neighboring group participation. The inclusion 4-C-methyl into 4-O-benzoyl galactopyranosyl donor enables nuclear magnetic resonance observation ion arising participation distal ester, with methyl influence attributed ester ground state conformation destabilization. We show that also influences side-chain conformation, enforcing gauche,trans gluco and galactopyranosides. Competition experiments reveal has only minor on rate reaction or 4-O-benzyl-galacto glucopyranosyl and, consequently, does result kinetic acceleration (anchimeric assistance). demonstrate stereoselectivity 4-O-benzoyl-4-C-methyl depends concentration additive (diphenyl sulfoxide) stoichiometry hence is borderline phenomenon competition standard glycosylation mechanisms. An analysis recent paper affirming remote pivalate presented alternative explanations for phenomena.

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

46
Catalytic Glycosylation for Minimally Protected Donors and Acceptors DOI

Qiu-Di Dang,

Yihui Deng, Tianyu Sun

et al.

Nature, Journal Year: 2024, Volume and Issue: 632(8024), P. 313 - 319

Published: June 17, 2024

Language: Английский

Citations

19
Guidelines for O-Glycoside Formation from First Principles DOI Creative Commons
Peter R. Andreana, David Crich

ACS Central Science, Journal Year: 2021, Volume and Issue: 7(9), P. 1454 - 1462

Published: Aug. 13, 2021

With a view to reducing the notorious complexity and irreproducibility of glycosylation reactions, 12 guidelines for choice concentration, temperature, counterions are adumbrated.

Language: Английский

Citations

66
Palladium catalysis enables cross-coupling–like S N 2-glycosylation of phenols DOI
Li‐Fan Deng, Yingwei Wang,

Shiyang Xu

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6673), P. 928 - 935

Published: Nov. 23, 2023

Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies carbohydrate functions would be advanced if glycosylation methods were as reliable modular palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels forming sp 2 -hybridized carbon centers whereas mostly builds 3 C–O linkages. We report platform through Pd-catalyzed S N displacement from phenols toward bench-stable, aryl-iodide–containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges an arylating agent (Csp electrophile) to glycosylating electrophile). This method inherits many merits cross-coupling reactions, including operational simplicity functional group tolerance. It preserves mechanism for various substrates is amenable late-stage commercial drugs natural products.

Language: Английский

Citations

31
Donor Preactivation-Based Glycan Assembly: from Manual to Automated Synthesis DOI
Wenlong Yao, Xin‐Shan Ye

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(11), P. 1577 - 1594

Published: April 16, 2024

Carbohydrates are called the third chain of life. participate in many important biochemical functions living species, and biological information carried by them is several orders magnitude larger than that nucleic acids proteins. However, due to intrinsic complexity heterogeneity carbohydrate structures, furnishing pure structurally well-defined glycans for functional studies a formidable task, especially homogeneous large-size glycans. To address this issue, we have developed donor preactivation-based one-pot glycosylation strategy enabling multiple sequential glycosylations single reaction vessel.The refers which glycosyl activated absence acceptor generate reactive intermediate. Subsequently, with same anomeric leaving group added, leading coupling reaction, then iterated rapidly achieve desired glycan reactor. The advantages include following: (1) unique chemoselectivity obtained after preactivation; (2) it independent reactivity donors; (3) multiple-step enabled without need intermediate purification; (4) only stoichiometric building blocks required complex protecting manipulations. Using protocol, range including tumor-associated antigens, various glycosaminoglycans,

Language: Английский

Citations

10
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
Recent advances in stereoselective 1,2-cis-O-glycosylations DOI Creative Commons
Akihiro Ishiwata, Katsunori Tanaka,

Jiaming Ao

et al.

Frontiers in Chemistry, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 19, 2022

For the stereoselective assembly of bioactive glycans with various functions, 1,2-

Language: Английский

Citations

30
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
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
Progress and challenges in the synthesis of sequence controlled polysaccharides DOI Creative Commons
Giulio Fittolani, Theodore Tyrikos‐Ergas, Denisa Vargová

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 17, P. 1981 - 2025

Published: Aug. 5, 2021

The sequence, length and substitution of a polysaccharide influence its physical biological properties. Thus, sequence controlled polysaccharides are important targets to establish structure-properties correlations. Polymerization techniques enzymatic methods have been optimized obtain samples with well-defined patterns narrow molecular weight distribution. Chemical synthesis has granted access full control over the length. Here, we review progress towards polysaccharides. For each class polysaccharides, discuss available synthetic approaches their current limitations.

Language: Английский

Citations

28