ABSTRACT
The development of a 1-hydroxybenzotriazole linker for the synthesis of heterocyclic derivatives is described, utilizing analytical construct methodology to facilitate the analysis of resin samples. A UV-chromophore-containing analytical construct enabled the accurate determination of resin loading and the automated monitoring of key reactions using only small quantities of resin. The syntheses of an array of isoxazole derivatives are reported.
ABSTRACT
The synthesis and application of a carbonyl-(13)C backbone amide linker are described. The labeled unit is conveniently mixed with commercial resins, providing a rapid means of monitoring chemistry performed with this linker on solid support using conventional (13)C NMR methods.
ABSTRACT
Analytical construct technology has been successfully applied to the single-bead analysis of a split-mix combinatorial library. Substrates can be released from the resin by conventional cleavage for biological screening. Alternatively, for the purpose of analysis and quality control, cleavage at an orthogonal construct linker produces an analytical fragment incorporating the substrate. This analytical fragmnent is highly sensitized to electrospray mass spectrometry (ESI-MS) and is easily identified by isotope labeling. The construct cleavage rendered readily visible even those compounds that clearly could not be seen by conventional cleavage and mass spectrometry analysis. A 1H NMR control experiment proved that the compounds cleaved conventionally were, however, present in the sample in good yield and purity. In view of the data obtained, we think that this is a significant and important step toward solving our current quality control problems.
Subject(s)
Combinatorial Chemistry Techniques , Databases, Factual , Amino Acids/chemistry , Carboxylic Acids/chemistry , Drug Design , Magnetic Resonance Spectroscopy , Microspheres , Models, Molecular , Polymers/chemical synthesis , Polymers/chemistry , Pyrimidines/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
[reaction: see text] An analytical construct resin, designed to aid the analysis of solid-phase chemistry, has been mixed in a small proportion with a conventional resin. The analytical construct ("reporter resin") contains two orthogonal linkers that allow cleavage of either the synthetic intermediates (at linker 2) or their analytically enhanced derivatives (at linker 1). The convenient and rapid monitoring of each step in the syntheses of representative library compounds was possible using small resin aliquots.
Subject(s)
Chemistry, Pharmaceutical , Resins, Plant/chemical synthesis , Chromatography, High Pressure Liquid , Molecular Structure , Resins, Plant/chemistryABSTRACT
The aim of this review is to give a compendium of colorimetric assays and spectrophotometric-based quantification methods applicable to solid-phase organic chemistry. Comprehensive experimental details for commonly employed color tests performed on solid support will be documented.
