Celebesides A−C and Theopapuamides B−D, Depsipeptides from an Indonesian Sponge That Inhibit HIV-1 Entry

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• 作者：Alberto Plaza ; Giuseppe Bifulco ; Jessica L. Keffer ; John R. Lloyd ; Heather L. Baker ; Carole A. Bewley
• 刊名：Journal of Organic Chemistry
• 出版年：2009
• 出版时间：January 16, 2009
• 年：2009
• 卷：74
• 期：2
• 页码：504-512
• 全文大小：327K
• 年卷期：v.74,no.2(January 16, 2009)
• ISSN：1520-6904

文摘

Six new depsipeptides belonging to two different structural classes, termed celebesides A−C and theopapuamides B−D, have been isolated from the marine sponge Siliquariaspongia mirabilis. Their structures were determined using extensive 2D NMR and ESI-MS/MS techniques. Celebesides are unusual cyclic depsipeptides that comprise a polyketide moiety and five amino acid residues, including an uncommon 3-carbamoyl threonine, and a phosphoserine residue in celebesides A and B. Theopapuamides B−D are undecapeptides with an N-terminal fatty acid moiety containing two previously unreported amino acids, 3-acetamido-2-aminopropanoic acid and 4-amino-2,3-dihydroxy-5-methylhexanoic acid. The relative configuration of the polyketide moiety in celebesides was resolved by J-based analysis and quantum mechanical calculations, the results of which were self-consistent. Celebeside A neutralized HIV-1 in a single-round infectivity assay with an IC₅₀ value of 1.9 ± 0.4 μg/mL while the nonphosphorylated analog celebeside C was inactive at concentrations as high as 50 μg/mL. Theopapuamides A−C showed cytotoxicity against human colon carcinoma (HCT-116) cells with IC₅₀ values between 2.1 and 4.0 μg/mL and exhibited strong antifungal activity against wildtype and amphotericin B-resistant strains of Candida albicans at loads of 1−5 μg/disk.