Cyclic Tetrapeptides via the Ring Contraction Strategy: Chemical Techniques Useful for their Identification

Cyclic tetrapeptides are a class of natural products that have been shown to have broad ranging biological activities and good pharmacokinetic properties. In order to synthesise these highly strained compounds a ring contraction strategy had previously been reported. This strategy was further optimised and a suite of techniques, including the Edman degradation and mass spectrometry/mass spectrometry, were developed to enable characterisation of cyclic tetrapeptide isomers. An NMR solution structure of a cyclic tetrapeptide was also generated. To illustrate the success of this strategy a library of cyclic tetrapeptides was synthesised.