Recent advances in site-selective functionalization of carbohydrates mediated by organocatalysts

Blaszczyk, Stephanie A.; Homan, Timothy C.; Tang, Weiping

doi:10.1016/j.carres.2018.11.012

Cited by 47 publications

(19 citation statements)

References 46 publications

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“…The preparation of high value‐added carbohydrates and building blocks for oligosaccharide synthesis still remains the most important scientific problem in carbohydrate chemistry . Regioselective acylation is of great importance in the synthesis of valuable oligosaccharide structural units because it facilitates the protection and deprotection of hydroxyl groups and the synthesis of target building blocks . Recently, many methods have been developed to make regioselective acylations highly efficient, green, and even controllable, and some metal catalysts and organic small molecules have been used for the regioselective acylation of carbohydrates and diols; for example, tin(IV), boron(IV), copper(II), silver(I), and iron catalysts have been recently reported , .…”

Section: Introductionmentioning

confidence: 99%

DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

Ren

Zhang

et al. 2019

Eur J Org Chem

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The 1,5‐diazabicyclo[4.3.0]non‐5‐ene (DBN)‐catalyzed regioselective acylation of carbohydrates and diols in ethyl acetate has been developed. The hydroxyl groups can be selectively acylated by the corresponding anhydride in EtOAc in the presence of a catalytic amount (as low as 0.1 equiv.) of DBN at room temperature to 40 °C. This method avoids metal catalysts and toxic solvents, which makes it comparatively green and mild, and it uses less organic base compared with other selective acylation methods. Mechanism studies indicated that DBN could catalyze the selective acylation of hydroxyl moieties through a dual H‐bonding interaction.

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Section: Introductionmentioning

confidence: 99%

DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

Ren

Zhang

et al. 2019

Eur J Org Chem

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“…Next, we sought to evaluate the performance of functionally complex nucleophiles in the site‐selective reaction catalyzed by C2 catalyst (Scheme 4). [23] Dexamethasone 24 , bearing a variety of functional groups and three hydroxyls, is an anti‐inflammatory and immunosuppressive corticosteroid that has been used as the drug to treat severe COVID‐19 patients [24] . Although there are three potential coupling sites in dexamethasone 24 , we hypothesized that a primary hydroxyl would be the preferred site.…”

Section: Resultsmentioning

confidence: 99%

A Mechanistic Probe into 1,2‐cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope

Nguyen

2021

Adv Synth Catal

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Phenanthroline, a rigid and planar compound with two fused pyridine rings, has been used as a powerful ligand for metals and a binding agent for DNA/RNA. We discovered that phenanthroline could be used as a nucleophilic catalyst to efficiently access high yielding and diastereoselective α‐1,2‐cis glycosides through the coupling of hydroxyl acceptors with α‐glycosyl bromide donors. We have conducted an extensive investigation into the reaction mechanism, wherein the two glycosyl phenanthrolinium ion intermediates, a 4C1 chair‐liked β‐conformer and a B2,5 boat‐like α‐conformer, have been detected in a ratio of 2:1 (β:α) using variable temperature NMR experiments. Furthermore, NMR studies illustrate that a hydrogen bonding is formed between the second nitrogen atom of phenanthroline and the C1‐anomeric hydrogen of sugar moiety to stabilize the phenanthrolinium ion intermediates. To obtain high α‐1,2‐cis stereoselectivity, a Curtin‐Hammett scenario was proposed wherein interconversion of the 4C1 chair‐like β‐conformer and B2,5 boat‐like α‐conformer is more rapid than nucleophilic addition. Hydroxyl attack takes place from the α‐face of the more reactive 4C1 β‐phenanthrolinium intermediate to give an α‐anomeric product. The utility of the phenanthroline catalysis is expanded to sterically hindered hydroxyl nucleophiles and chemoselective coupling of an alkyl hydroxyl group in the presence of a free C1‐hemiacetal. In addition, the phenanthroline‐based catalyst has a pronounced effect on site‐selective couplings of triol motifs and orthogonally activates the anomeric bromide leaving group over the anomeric fluoride and sulfide counterparts.

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“… 29 , 30 While the former focused on small molecule-based lysosome targeting degraders, 29 the latter investigated antibody-based degraders for extracellular protein targets. 30 Inspired by Bertozzi’s pioneering work on LYTACs based on CI-M6PR and due to our interest in both targeted protein degradation 31 − 34 and carbohydrate chemistry, 35 , 36 we initiated the investigation of ASGPR-mediated targeted protein degradation using chimeric molecules bearing a trivalent GalNAc ligand as liver cell-specific degraders for extracellular proteins including membrane proteins ( Figure 1 ). Since liver is the major place for protein catabolism, selectively delivering undesired proteins to the liver for degradation can be potentially advantageous over ubiquitously delivery of protein targets to various types of cells unselectively for many therapeutic applications.…”

Section: Introductionmentioning

confidence: 99%

Development of Triantennary N-Acetylgalactosamine Conjugates as Degraders for Extracellular Proteins

et al. 2021

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Targeted protein degradation (TPD) technology has drawn significant attention from researchers in both academia and industry. It is rapidly evolved as a new therapeutic modality and also a useful chemical tool in selectively depleting various protein targets. As most efforts focus on cytosolic proteins using PROteolysis TArgeting Chimera (PROTAC), LYsosome TArgeting Chimera (LYTAC) recently emerged as a promising technology to deliver extracellular protein targets to lysosome for degradation through the cation-independent mannose-6-phosphate receptor (CI-M6PR). In this study, we exploited the potential of the asialoglycoprotein receptor (ASGPR), a lysosomal targeting receptor specifically expressed on liver cells, for the degradation of extracellular proteins including membrane proteins. The ligand of ASGPR, triantennary N -acetylgalactosamine (tri-GalNAc), was conjugated to biotin, antibodies, or fragments of antibodies to generate a new class of degraders. We demonstrated that the extracellular protein targets could be successfully internalized and delivered into lysosome for degradation in liver cell lines specifically by these degraders. This work will add a new dimension to TPD with cell type specificity.

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Recent advances in site-selective functionalization of carbohydrates mediated by organocatalysts

Cited by 47 publications

References 46 publications

DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

DBN‐Catalyzed Regioselective Acylation of Carbohydrates and Diols in Ethyl Acetate

A Mechanistic Probe into 1,2‐cis Glycoside Formation Catalyzed by Phenanthroline and Further Expansion of Scope

Development of Triantennary N-Acetylgalactosamine Conjugates as Degraders for Extracellular Proteins

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