Despite growing interest for therapeutic and other biological applications, cyclic peptidomimetics are challenging to synthesize. As reported by the lab of Andrei Yudin, (N-isocyanoimino)triphenylphosphorane (Pinc ) enables zwitterionic-controlled generation of peptide macrocyles from linear peptides and aldehydes. Containing a 1,3,4-oxadiazole, the resulting peptide exhibits both improved membrane permeability, lipophilicity, and aqueous solubility. Different functional groups can be introduced by varying the aldehyde, and initial work used propionaldehyde (538124), phenylacetaldehyde (107395), and isovaleraldehyde (146455).
The Yudin laboratory is known for the development of amphoteric molecules and their application in synthesis. The corresponding reagents possess nucleophilic and electrophilic functional groups that do not prematurely react with each other.