Determination of the amino linkage of the D-Dab residue of the cyclic lipo-octapeptide occidiofungins A-D and the antifungal activity of their analogues.

Recently, the demand for new antifungal drugs has increased due to the presence of antimicrobial resistant bacteria and their side effects. Occidiofungins (Ocfs) are cyclic lipo-octapeptides that possess unusual amino acids and potent antifungal activities. However, the chemical structure of the 2,4-diamino butyric acid (Dab) residue in the backbone of Ocfs has not been clarified thus far. Therefore, we conducted a structural analysis of the tripeptides around the Dab residue in Ocfs using 1H-NMR spectroscopy. We determined that the D-Dab residue in the peptide backbone of Ocfs has an α-amino linkage. Additionally, we found that Ocf A (5) and Bk-1119 have the same chemical structure. Moreover, the analogue possessing D-αDab (13) showed potent antifungal activity against A. oryzae.

Synthesis and Configuration Confirmation of the ATHOD Fatty Amino Acid Residue in the Burkholdines.

Eight possible diastereomers of the 3-amino-5,6,7-trihydroxy octadecanoic acid (ATHOD) moiety of the burkholdines (Bks) have been synthesized and their configurations assigned. Though the relative configuration of the triol in the ATHOD residue of the Bks was proposed to be anti-anti-anti in the literature, 1H NMR spectra of our synthesized anti-anti-anti ATHOD derivative was inconsistent with that of the isolated ATHOD residue, suggesting that the assignment of the relative configuration of that residue in the literature was incorrect. However, by comparison of the NMR data of our ATHOD derivatives with that of configurationally defined samples of 2-amino-4-pentanol using Kishi's NMR database method, we conclude that the absolute configuration of the ATHOD moiety is (3R,5S,6R,7S). In addition, we revealed that the ATHOD residue present in the occidiofungins A-D has the same configuration as that in all the Bks.