Enantioselective synthesis of molecules with multiple stereogenic elements.

This review explores the fascinating world of molecules featuring multiple stereogenic elements, unraveling the different strategies designed over the years for their enantioselective synthesis. Specifically, (dynamic) kinetic resolutions, desymmetrisations and simultaneous installation of stereogenic elements exploiting either metal- or organo-catalysis are the principal approaches to efficiently create and control the three-dimensional shapes of these attractive molecules. Although most molecules presented in this review possess a stereogenic carbon atom in combination with a stereogenic axis, other combinations with helices or planes of chirality have started to emerge, as well as molecules displaying more than two different stereogenic elements.

Beyond Rule-of-five: Permeability Assessment of Semipeptidic Macrocycles.

Compounds beyond the rule-of-five are generating interest as they expand the molecular toolbox for modulating targets previously considered "undruggable". Macrocyclic peptides are an efficient class of molecules for modulating protein-protein interactions. However, predicting their permeability is difficult as they differ from small molecules.