Dynamic combinatorial chemistry with hydrazones: libraries incorporating heterocyclic and steroidal motifs

Abstract

We expand the possibilities in hydrazone based dynamic combinatorial chemistry with a series of new building blocks incorporating heterocyclic motifs. The synthetic procedure allows efficient access to building blocks with the general structure (MeO)₂CH-Heterocycle-C(O)NHNH₂, originating from heterocycles with an amine and an ester functionality. The equilibrium distribution of macrocyclic N-acyl hydrazones formed upon deprotection of the building blocks with TFA in organic solvents is reported. The mixing behaviour of these heterocycle-based building blocks with our cholate-based building blocks is described, particularly the observation of kinetic intermediates that disappear following ‘proof-reading’.