Fluorous mixture synthesis of two libraries with hydantoin-, and benzodiazepinedione-fused heterocyclic scaffolds.
Diversity-oriented synthesis (DOS) and fluorous mixture synthesis (FMS) are two aspects of combinatorial chemistry. DOS generates library scaffolds with skeletal, substitution, and stereochemistry variations, whereas FMS is a highly efficient tool for library production. The combination of these two aspects in solution-phase synthesis of two novel heterocyclic compound libraries is presented in this paper. Mixtures of different fluorous amino acids undergo [3 + 2] cycloadditions followed by postcondensation reactions. The mixtures are then demixed by fluorous HPLC. Fluorous tags are removed by cyclization to afford hydantoin- and benzodiazepinedione-fused heterocyclic compounds as individual, pure, and structurally defined molecules. The application of MS-directed HPLC purification and parallel four-channel LC/MS analysis further increases the efficiency of FMS.
Zhang
Wei
W
Fluorous Technologies, Inc., University of Pittsburgh Applied Research Center, 970 William Pitt Way, Pittsburgh, Pennsylvania 15238, USA. w.zhang@fluorous.com
Lu
Yimin
Y
Hiu-Tung Chen
Christine
C
Zeng
Lu
L
Kassel
Daniel B
DB
D001569:Benzodiazepines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D005461:Fluorine / Q000737:chemistry; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry*; D006827:Hydantoins / Q000737:chemistry*; D013058:Mass Spectrometry
D006575:Heterocyclic Compounds, 3-Ring; D006576:Heterocyclic Compounds, 4 or More Rings; D006827:Hydantoins; D001569:Benzodiazepines; D005461:Fluorine