Drug discovery is accelerated by high-throughput screening, where libraries of synthetic compounds are rapidly assessed for biological activity. While largely successful, over-utilized synthetic methods have narrowed the structural diversity of drug fragments utilized in screens. Synthetic peptide therapeutics address the lack of structural diversity in drug discovery and are endowed with features beyond those in naturally occurring peptides. The concept of “click chemistry” aligns with high throughput screening for drug development; however, it is able to generate and screen combinatorial libraries via catalyst-free “click” cycloadditions under ambient/aqueous conditions, unlike current chemical mechanisms. Researchers and drug developers can actively utilize these libraries to screen synthetic peptides for anticancer activity, leading to combinatorial therapeutic development. This provides novel chemical strategies and scaffolds for the generation of cancer therapeutics and biomaterials, and advancement of knowledge pertinent to protein interactions. Thus, there is the need to find the next “click” reactions to create these libraries and further development.
Researchers at the University of New Mexico have deemed sulfur fluoride exchange (SuFEx) to be the next “click” reaction. SuFEx-able “hubs” enable rapid generation of compound libraries via divergent syntheses. Herein, the researchers have reported a facile strategy to access SuFExable NH-pyrazoles via strain and catalyst-free cycloadditions of stabilized diazo compounds under mild conditions. Subsequent SuFEx proceeds efficiently with various N- and O-nucleophiles. While the “click” strategy focuses on the modular assembly of building blocks, the properties of generated linkages are of growing interest. Facile generation of starting materials from readily available precursors, distinct advantages of diazo compounds, and highly selective reactivity enables myriad opportunities for multistage diversification strategies that remain true to the “click” mantra. Overall, the SuFEx reactions enable the synthesis of compounds for use in chemical synthesis, materials chemistry, and chemical biology.
- Efficient reactivity allows for high-throughput screening
- Divergent synthesis enables the rapid generation of compound libraries
- Advances development of therapeutics and biomaterials
- Pharmaceuticals/ Biomedicine
- Environmental Management
- Synthetic Chemistry/Biology Research
- High-Throughput Screening
Name: Gregg Banninger