Scaffolding-Induced Property Modulation of Chemical Space

Physicochemical
property switching of chemical space is of great importance for optimization
of compounds, for example, for biological activity. Cyclization is
a key method to control 3D and other properties. A two-step approach,
which involves a multicomponent reaction followed by cyclization,
is reported to achieve the transition from basic moieties to charge
neutral cyclic derivatives. A series of multisubstituted oxazolidinones,
oxazinanones, and oxazepanones as well as their thio and sulfur derivatives
are synthesized from readily available building blocks with mild conditions
and high yields. Like a few other methods, MCR and cyclization allow
for the collective transformation of a large chemical space into a
related one with different properties.