Synthesis of macrocyclic analogues of the neuroprotective agentglycyl-l-prolyl-l-glutamic acid (GPE)

Abstract

The syntheses of seven macrocyclic analogues of the neuroprotective tripeptide glycyl-L-prolyl-L-glutamic acid (GPE) 1 are described. Macrocycles 6 and 7 mimic the cis conformer of GPE whereas macrocycles 2–5, 8, and 9 mimic the trans conformer of GPE. The macrocyclic peptides of well-defined geometry were prepared via Grubbs ring closing metathesis of an appropriate diene precursor. In turn each of the diene precursors were prepared from the readily available allyl-substituted amino acid building blocks 12, 13, 14, 27, 36 and 51.