Expanding the Scope of Oligo-pyrrolinone–Pyrrolidines as Protein–Protein Interface Mimics

Oligo-pyrrolinone–pyrrolidines
(generic structure 1) have the potential to interfere
with protein–protein
interactions (PPIs), but to reduce this to practice it is necessary
to be able to synthesize these structures with a variety of different
side chains corresponding to genetically encoded proteins. This paper
describes expansion of the synthetic scope of 1, the
difficulties encountered in this process, particularly issues with
epimerization and slow coupling rates, and methods to overcome them.
Finally, spectroscopic and physicochemical properties as well as proteolytic
stabilities of molecules in this series were measured; these data
highlight the suitability of oligo-pyrrolinone–pyrrolidines
for the development of pharmacological probes or pharmaceutical leads.