Structure, absolute configuration, and conformational study of 12-membered macrolides from the fungus dendrodochium sp. associated with the sea cucumber holothuria nobilis selenka

Peng Sun, Dong Xiao Xu, Attila Mándi, T. Kurtán, Tie Jun Li, Barbara Schulz, Wen Zhang

Research output: Article

88 Citations (Scopus)

Abstract

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collect0ed from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium. The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of β-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

Original languageEnglish
Pages (from-to)7030-7047
Number of pages18
JournalJournal of Organic Chemistry
Volume78
Issue number14
DOIs
Publication statusPublished - júl. 19 2013

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Macrolides
Fungi
Derivatives
Polyketides
Spectroscopic analysis
Bioassay
Biosynthesis
X ray analysis
Dichroism
Density functional theory
Conformations
Diffraction
Single crystals
X rays

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Structure, absolute configuration, and conformational study of 12-membered macrolides from the fungus dendrodochium sp. associated with the sea cucumber holothuria nobilis selenka. / Sun, Peng; Xu, Dong Xiao; Mándi, Attila; Kurtán, T.; Li, Tie Jun; Schulz, Barbara; Zhang, Wen.

In: Journal of Organic Chemistry, Vol. 78, No. 14, 19.07.2013, p. 7030-7047.

Research output: Article

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abstract = "Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collect0ed from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium. The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of β-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.",
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