Efficient Synthesis of Structurally Diverse Diazabicycloalkanes: Scaffolds for Modular Dipeptide Mimetics with Tunable Backbone Conformations

Abstract

AbstractA stereoselective synthesis of new dipeptide mimetics based on a diazabicycloalkane scaffold is reported. The route starts from enantiomerically pure azabicycloalkenes 1 that are bis(hydroxylated) and coupled N‐terminally to a second amino acid. The key step of the reaction sequence is an oxidative cleavage of the resulting dipeptides 5 to give highly functionalised diazabicycloalkanes 6, which can be easily converted into a number of dipeptide mimetics with defined and variable stereochemistry and a number of different amino acid side chains. The backbone dihedral angles within these dipeptide mimetics can be tuned by varying the stereochemistry and the ring sizes of the diazabicycloalkane scaffold. The syntheses of conformationally constrained dipeptide analogues in four to five steps are presented. With the syntheses of dipeptide mimetics 19a−c, suitable linker moieties for conjugation of diazabicycloalkanes to other functional molecules like markers or solid phases are introduced, making these compounds modular dipeptide mimetics that might find applications as modular ligands or as solid‐phase‐attached scaffolds in combinatorial chemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)