Isolation and Total Synthesis of Albu­peptins A-D: 11-Residue Peptaibols from the FungusGliocladium album

Four new 11‐ mer peptaibols, named albupeptins A–D ( 1 – 4 ), were isolated from cultures of the fungus Gliocladium album . Their structures were elucidated on the basis of 1D and 2D NMR spectroscopy, as well as ESI‐HRMS n analysis. The sequence of albupeptin A ( 1 ) was thus identified as Ac‐Aib 1 ‐Aib 2 ‐Val 3 ‐Leu 4 ‐Aib 5 ‐Pro 6 ‐Iva 7 ‐Leu 8 ‐Gln 9 ‐Aib 10 ‐Leuol 11 . Albupeptins B ( 2 ) and C ( 3 ) feature an exchange of Aib 5 by Iva 5 and of Aib 1 by Iva 1 , respectively, and albupeptin D ( 4 ) contains both Iva 1 and Iva 5 residues. The stereochemistry of the isolated peptaibols 1 – 4 was unambiguously assigned by 1 H NMR chemical shift analysis in conjunction with solid‐phase peptide synthesis. By using this approach, the absolute configuration of the Iva residues in albupeptins A ( 1 ) and C ( 3 ) was determined to be D , whereas albupeptins B ( 2 ) and D ( 4 ) feature an additional Iva 5 residue with an L configuration. Thus, albupeptins B ( 2 ) and D ( 4 ) belong to the rare class of peptaibols that have both stereoisomers of Iva in the same sequence.