ABSTRACT
Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.
Subject(s)
Glycine/analogs & derivatives , Glycine/chemical synthesis , Imidazoles/chemical synthesis , Databases as Topic , Glycine/chemistry , Imidazoles/chemistry , Indicators and Reagents , Ketones/chemical synthesis , Ketones/chemistry , Models, Molecular , Resins, PlantABSTRACT
The design and rationale of some novel chiral stationary phases (CSPs) are discussed with respect to methods for determining enantiomeric purity, absolute configuration and for obtaining enantiomerically pure materials by liquid chromatography. The commercially-available dinitrobenzoylamino CSP type 1 is discussed with respect to the chiral recognition mechanisms which may operate in the resolution of some polycyclic and heterocyclic aromatic molecules and some benzodiazepines. N-Acyl alpha-arylalkylamines are also employed as models to formulate mechanisms for the chiral properties of type 1 CSPs in terms of enantiomeric stacking of the most stable conformations in solution. The properties of new types of 'reciprocal' CSPs are discussed and illustrated by enantiomeric separation of some amino acid and amino phosphoric acid derivatives, and by the separation of the following enantiomeric drugs as their 3,5-dinitrobenzoyl derivatives: metoprolol, oxoprenolol, ephedrine and alprenolol.
