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Organic-Fluorous Phase Switches: A Fluorous Amine Scavenger for Purification in Solution Phase Parallel Synthesis
Bruno Linclau1, Ashvani K. Sing, Dennis P. Curran
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 and Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
The Journal of Organic Chemistry
|October 25, 2001
Summary
A novel fluorous amine scavenger simplifies automated urea synthesis by efficiently removing excess isocyanates. This method yields high-purity ureas, some showing ion channel modulation abilities, offering a versatile tool for drug discovery.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Materials Science
Background:
- Automated synthesis requires efficient methods for removing excess reagents.
- Fluorous tags offer unique solubility properties for purification.
- Urea compounds are important pharmacophores with diverse biological activities.
Purpose of the Study:
- To synthesize a fluorous amine scavenger for automated parallel synthesis.
- To apply the scavenger in the synthesis of a urea library.
- To evaluate the biological activity of the synthesized ureas.
Main Methods:
- Synthesis of a fluorous amine scavenger: [(C6F13CH2CH2)3SiCH2CH2CH2]2NH.
- Robotic automated solution phase parallel synthesis of ureas using organic amines and excess isocyanates.
- Purification via fluorous-organic liquid-liquid extraction to remove scavenger-isocyanate adducts.
Main Results:
- Successful synthesis of the fluorous amine scavenger.
- High yields and purities of organic urea products achieved after extraction.
- Demonstrated tolerance of ionizable functional groups and product solubility variations.
- Preliminary biological evaluation revealed ion channel modulation abilities in several synthesized ureas.
Conclusions:
- The fluorous amine scavenger is effective for automated urea library synthesis.
- Fluorous-organic extraction provides a robust purification method for ureas.
- The synthesized ureas represent potential drug candidates for ion channel modulation.