Modular synthesis of functional libraries by accelerated SuFEx click chemistry

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Chemical Biology

Background:

• SuFEx (Sulfur(VI) Fluoride Exchange) click chemistry offers a robust platform for molecular construction.
• Accelerated SuFEx Click Chemistry (ASCC) enhances reaction kinetics and product yields.
• Efficient synthetic methods are crucial for discovering novel functional molecules and drug candidates.

Purpose of the Study:

• To demonstrate the utility of Accelerated SuFEx Click Chemistry (ASCC) for synthesizing functional molecules.
• To showcase ASCC as a tool for late-stage derivatization of bioactive compounds.
• To explore the application of ASCC in the synthesis of novel anticancer agents.

Main Methods:

• Utilized ASCC for coupling aryl and alkyl alcohols with SuFEx-compatible functional groups.
• Applied ASCC for late-stage derivatization of bioactive molecules.
• Performed array synthesis of sulfonate-linked microtubule targeting agents (MTAs) using ASCC.

Main Results:

• ASCC demonstrated favorable kinetics and high product yields.
• The ASCC reaction proved versatile for late-stage functionalization.
• Synthesized MTAs exhibited potent nanomolar anticancer activity against multidrug-resistant cancer cell lines.

Conclusions:

• ASCC is a powerful and efficient method for molecular synthesis and functionalization.
• ASCC is a practical tool for drug discovery, particularly for developing novel anticancer therapeutics.
• The developed MTAs show significant promise for treating multidrug-resistant cancers.