Stereoselective Solid-Phase Synthesis of a Triaza Tricyclic Ring System: A New Chemotype for Lead Discovery

Sequential pyrrolidine and hydantoin ring-forming reactions have been applied in the stereoselective solid-phase synthesis of a conformationally constrained, tricyclic triazacyclopenta[c]pentalene scaffold. These novel compounds share the structural complexity characteristic of certain alkaloid natural products and represent a source of chemical diversity that complements more traditional classes of heterocyclic compounds of interest as potential pharmaceutical agents. They are assembled in a 12-step reaction sequence from 4 variable building blocks by combining an intramolecular azomethine ylide cycloaddition reaction with a final cyclative cleavage from resin.