Organic & Biomolecular Chemistry 2006-07-21

Synthesis of macrocyclic analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE).

Paul W R Harris, Margaret A Brimble

Index: Org. Biomol. Chem. 4(14) , 2696-709, (2006)

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Abstract

The syntheses of seven macrocyclic analogues of the neuroprotective tripeptide glycyl-L-prolyl-L-glutamic acid (GPE) 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.