6.

Structures of the Aspartocin Antibiotics§ - A Consideration of Requirements for Cyclopeptide Structures

Fangming Kong, Kasia Janota, Joseph S. Ashcroft and Guy T. Carter

Wyeth Research‡,  401 N. Middletown Road, Pearl River, NY 10965, USA

Abstract: Three lipocyclopeptides, aspartocins A (1), B (2), and C (3), were obtained   from the aspartocin complex by reversed-phase HPLC separation. Their structures were elucidated by spectroscopic studies coupled with the previously published chemical degradation results. All three compounds, 1, 2, and 3, share the same cyclic decapeptide core of cyclo(Dab2-Pip3-MeAsp4-Asp5-Gly6-Asp7-Gly8-Dab9-Val10-Pro11-). They differ only in the side chain moiety corresponding to Asp1-isotetradecenoic acid, Asp1-anteisotetradecenoic acid, and Asp1-isotridecenoic acid for aspartocins A, B, and C, respectively. The cyclic substructure of aspartocins contains two D-amino acid residues, and the geometry of the peptide linkages appears to be all trans including the two tertiary amide bonds. The result is consistent with the hypothesis that a normal peptide to be cyclic requires D-configured residues or cis amide bond(s) incorporated.

Keywords: Lipopeptide antibiotics; cyclopeptide requirement; trans and cis amide bonds; L- and D-amino acid residues; pipecolic acid conformation; NMR spectroscopy