Related Experiment Video
Updated: Jul 14, 2026
06:00
One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates
Published on: January 15, 2018
Tautomeric modification of GlcNAc-thiazoline
Spencer Knapp1, Mohannad Abdo, Kehinde Ajayi
1Department of Chemistry and Chemical Biology, Rutgers-The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA. spencer.knapp@rutgers.edu
Organic Letters
|May 19, 2007
Summary
Researchers modified O-GlcNAcase (OGA) inhibitors, creating selective compounds for diabetes and neurodegeneration research. A novel radical addition/fragmentation reaction was also discovered.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Enzyme Inhibition
Background:
- O-GlcNAcase (OGA) is an enzyme implicated in diseases like diabetes and neurodegeneration.
- GlcNAc-thiazoline is a known OGA inhibitor, but requires modification for targeted applications.
Purpose of the Study:
- To synthesize novel functionalized GlcNAc-thiazoline derivatives.
- To evaluate the selectivity of these derivatives against OGA and human hexosaminidase.
- To discover new synthetic methodologies for inhibitor development.
Main Methods:
- Modification of GlcNAc-thiazoline via imine-to-enamine conversion.
- Electrophilic and radical addition reactions to introduce various functional groups (Xn = D3, F, N3, OH, SMe, COCF3, CF3).
- Assay of enzyme inhibition against O-GlcNAcase and human hexosaminidase.
Main Results:
- Several functionalized GlcNAc-thiazolines were successfully synthesized.
- A subset of these compounds demonstrated high selectivity for OGA inhibition over human hexosaminidase.
- A new radical addition/fragmentation reaction involving N-(trifluoroacetyl)enamine was identified.
Conclusions:
- The developed GlcNAc-thiazoline derivatives show significant promise as research tools for studying OGA.
- These selective inhibitors could aid in understanding the roles of OGA in diabetes and neurodegenerative diseases.
- The discovery of a new radical reaction expands synthetic possibilities for inhibitor design.
Related Concept Videos
01:24Oligosaccharide Assembly
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
01:24Phase II Reactions: Acetylation Reactions
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
01:27Glucose Transporters
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
02:36Transfer RNA Synthesis
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
01:24Phase II Reactions: Glucuronidation
Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
01:19Amines to Amides: Acylation of Amines
Various carboxylic acid derivatives (such as acid chlorides, esters, and anhydrides) can be used for the acylation of amines to yield amides. The reaction requires two equivalents of amines. The first amine molecule functions as a nucleophile and attacks the carbonyl carbon to produce a tetrahedral intermediate. This is followed by the loss of the leaving group and restoration of the C=O bond.
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary amide...