Nuclear magnetic resonance study of ring conformations of cyclic tetradepsipeptide AM‐toxins and related peptides

Cyclic tetradepsipeptides, AM‐toxin I and II, are the host‐specific phytotoxins of Alternaria mali. In order to elucidate conformation‐toxicity relationships, we analyzed the 270‐MHz proton nmr spectra of AM‐toxins and hydrogenated analogs, ( D ‐Ala 2 )AM‐toxin I (toxic) and ( L ‐Ala 2 )AM‐toxin I (not toxic), in (C 2 H 3 ) 2 SO. These cyclic tetradepsipeptides do not contain N‐substituted amino acid residues, and all the peptide and ester groups have been found to be transoid. Two conformers with very unequal populations have been found for AM‐toxin I and II; the C β C α CO conformations of the Dha 2 residues are nonplanar S‐ trans in the major conformer and nonplanar S‐ cis in the minor conformer. Only one ring conformation has been found for each of ( L ‐Ala 2 ) and ( D ‐Ala 2 )AM‐toxin I. ( L ‐Ala 2 )AM‐toxin I takes a C 4 ‐type ring conformation; all the CO groups and C α ‐H bonds are oriented to the same side of the ring. ( D ‐Ala 2 )AM‐toxin I takes a new ring conformation; the side chain and CO group of the L ‐Amp 1 residue are oriented to the same side of the ring. This new conformation is also found for the major conformers of AM‐toxin I and II and thus appears to be required for the toxicity. The ring conformations of Tyr(OCH 3 ) 1 ‐bearing analog tetradepsipeptides have been found to be much the same as those of Amp 1 ‐bearing depsipeptides. Furthermore, on the basis of the two distinct conformations of ( D ‐Ala 2 ) and ( L ‐Ala 2 )AM‐toxin I, an empirical rule is proposed for the stable ring conformations of cyclic tetra‐ D , L ‐peptides, not containing N‐substituted amino acid residues.