Synthetic studies on quinoxaline antibiotics. III. Synthesis of nortriostin A, a triostin A analog lacking N-methyl groups on the cystine and valine residues

Article abstract of DOI:10.1246/bcsj.57.2211

Nortriostin A, which is an analog of a cyclic octadepsipeptide antibiotic triostin A and contains one cystine and two valine residues substituted for the N,N'-dimethylcystine and N-methylvaline residues of the antibiotic, was synthesized with Z-D-Ser[Boc-Ala-Cys(MeBzl)-Val]-OH and Z-D-Ser[H-Ala-Cys(MeBZ)-Val]-OTce as key intermediates. The synthetic analog showed no antimicrobial activity at a concentration of 100 μg/ml and was found to exist as a single structure in solution as examined by ¹H-NMR spectroscopy. The latter observation suggests that the conformer equilibrium known to occur with triostin A is a consequence of the presence of N-methyl peptide bonds in the antibiotic molecule. Nortriostin A, which is an analog of a cyclic octadepsipeptide antibiotic triostin A and contains one cystine and two valine residues substituted for the N,N prime -dimethylcystine and N-methylvaline residues of the antibiotic, was synthesized with Z-//D-Ser left bracket Boc-Ala-Cys(MeBzl)-Val right bracket -OH and Z-//D-Ser left bracket H-Ala-Cys(MeBzl)-Val right bracket -OTce as key intermediates. The synthetic analog showed no antimicrobial activity at a concentration of 100 mu g/ml and was found to exist as a single structure in solution as examined by **1H-NMR spectroscopy. The latter observation suggests that the conformer equilibrium known to occur with triostin A is a consequence of the presence of N-methyl peptide bonds in the antibiotic molecule.