Cyclic Peptides. IV. Synthesis of Diastereomeric Dihydro-AM-toxin I and Its Analogs

Diastereomeric cyclotetradepsipeptides [l-Ala2]– and [d-Ala2]–AM-toxin I, corresponding to the hydrogenated products of AM-toxin I, were synthesized by the conventional method and their biological activities were tested. [d-Ala2]–AM-toxin I exhibits weak but recognizable necrotic activity (5–10 μg/ml) on apple leaves. [l-Ala2]–AM-toxin I is inactive even in a high concentration of 100 μ/ml. The results of NMR and ORD measurements of [d-Ala2]–AM-toxin I and [l-Tyr(Me)1, d-Ala2]–AM-toxin indicates the presence of a common conformer. The results on [l-Ala2]–AM-toxin I and [l-Tyr(Me)1, l-Ala2]–AM-toxin revealed the presence of more than two conformers, the predominant conformation differing from that of d-isomers. Difference in activity between [d-Ala2]– and [l-Ala2]–AM-toxin I can be attributed to the difference in conformation of the diastereomers.