Abstract
The KF, sucrose (table sugar) exploited as quenching system in solution phase parallel synthesis. Excess of electrophiles were covalently trapped with hydroxyl functionality of sucrose and due to polar nature of sucrose derivative was solubilize in water. Potassium fluoride used to convert various excess electrophilic reagents such as acid chlorides, sulfonyl chlorides, isocyanates to corresponding fluorides, which are less susceptible for hydrolysis and subsequently sucrose traps these fluorides and dissolves them in water thus removing them from reaction mixture. Various excess electrophilic reagents such as acid chlorides, sulfonyl chlorides, and isocyanates were quenched successfully to give pure products in excellent yields.
Highlights
The generation and use of combinatorial chemical libraries for the identification of novel chemical leads or for optimization of a promising lead candidate has emerged as a potentially powerful tool for acceleration of the drug discovery process (Terrett et al 1995; Gallop et al 1994; Gordon et al 1994; Janda 1994; Pavia et al 1993)
The screening of large number of compounds can be quickly lead to early structure-activity relationships (SARs), and may provide a practical starting point for drug discovery program, where little or no information is known about the target
The excess of acid chlorides can be quenched using aqueous Sodium carbonate, while few aromatic acid chlorides do not get quenched in aqueous base and remain intact; but can be effectively quenched by KF sucrose quenching system (Table 1)
Summary
The generation and use of combinatorial chemical libraries for the identification of novel chemical leads or for optimization of a promising lead candidate has emerged as a potentially powerful tool for acceleration of the drug discovery process (Terrett et al 1995; Gallop et al 1994; Gordon et al 1994; Janda 1994; Pavia et al 1993). The amide and sulfonamide functionalities are the key structural moieties in many pharmaceutically active compounds such as paracetamol (analgesic and antipyretic), nateglinide (for treatment of type 2 diabetes), probenecid (uricosuric drug), and sotalol (for cardiac arrhythmias) (Fig. 1). Solution-phase parallel synthesis is an excellent way to form libraries of small molecules containing amide, sulfonamide and urea functionalities. During the synthesis of library, the chemistry for solution phase parallel synthesis require complete conversion of reactants with little or no formation of by-products or impurities to simplify the tedious purification processes. The solid phase synthesis offers benefit of easy and fast purification to separate excess reagents and side products from the desired compounds attached to the insoluble carrier. We report sucrose as readily available, environment friendly and cost effective novel quenching agent for the solution phase parallel synthesis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
