Synthesis and Conformational Analysis of the Slime-Mold Acrasin Glorin

Abstract

The chemotactic dipeptide for the slime-mould Polysphondylium violaceum, glorin (N- propionyl-y-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 Cα,Cβ 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 Ca,Cβ coupling constants were performed and, from these, significantly different relative populations for the three staggered conformations about the Glu-Ca,Cβ 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.