An aldol-based build/couple/pair-strategy for the synthesis of medium- and large-sized rings: discovery of macrocyclic histone deacetylase inhibitors

An aldol-based build/couple/pair (B/C/P) strategy is used for generating a collection of stereochemically and skeletally diverse small molecules. The screening of the library of macrolactams has led to the discovery of a novel class of histone deacetylase inhibitors, which has displayed mixed enzyme inhibition, and has led to increased levels of acetylation in a primary mouse neuron culture.