Synthesis and conformational analysis of the slime-mould acrasin glorin

The chemotactic dipeptide for the slime-mould Polysphondylium violaceum, glorin (N-propionyl-γ-L-glutamyl-l-ornithine-δ-lac ethyl ester) (8), was synthesized convergently in five steps with 41% overall yield, starting from l-ornithine hydrochloride (1) and l-glutamic acid γ-benzyl ester (4).¹H n.m.r. spectral analysis led to the conclusion that the propionamide and the γ-l-glutamyl amide bonds both undergo slow cis-trans isomerism in solution at room temperature. From a Karplus-type analysis of the values of the C_α, C_β coupling constants at the lactam chiral carbon, it was concluded that the six-membered ring can adopt either a half-chair or half-boat conformation, but it is not clear which. Similar calculations for the glutamyl C_α, C_β coupling constants were performed and, from these, significantly different relative populations for the three staggered conformations about the Glu-C_α, C_β bond were suggested. Receptor-binding studies showed that glorin did not bind significantly to any of the six receptors studied, including opioid, dopamine, central benzodiazepine, peripheral benzodiazepine, α₁-adrenoceptor and α₂-adrenoceptor sites.