DESIGN, SYNTHESIS, AND EVALUATION OF A DEPSIPEPTIDE MIMIC OF TENDAMISTAT

The cyclic hexadepsipeptide framework of enniatin B was identified as a template matching the beta-turn tripeptide of tendamistat. The modif ied analog 1 was synthesized as a tendamistat mimic and compared to th e acyclic derivative 2 and the tripeptide Ac-Try-Arg-Tyr-OMe. These co mpounds were assembled from the dimeric esters 3-5. As an inhibitor of alpha-amylase, 1 is twice as potent as 2 and comparable to the tripep tide. NMR studies of 1 reveal four conformers in equilibrium in a 50:2 5:15:10 ratio; the ring conformation of the major component is similar to that of the enniatin B template, with the cis geometry of the alph a-hydroxyisovaleryl-N-methylvaline amide linkage; the other conformers differ in the position or presence of the cis amide linkage.