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Chalasoergodimers A-E, heterodimers with multiple polymerization modes from a marine-derived Chaetomium sp. fungus
Ze-Hong Lin1, Han-Wen Shan1,2, Li-Kun Yang3
1College of Pharmaceutical Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnostics of Education Ministry of China, State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei University, Baoding, 071002, People's Republic of China.
Abstract:
Five new heterodimers, chalasoergodimers A-E (1-5), and three known heterodimers (6-8), along with four chaetoglobosin monomers (9-12), were isolated from a marine-derived Chaetomium sp. fungus. The structures of new compounds 1-5 were elucidated by HRESIMS, NMR, chemical calculated 13C NMR and ECD methods. Among them, compound 1 was derived from C-2' substitution of chaetoglobosin Fex (9) with ergosta-4,6,8(14),22-tetraen-3β-ol, representing a new dimerization mode among chaetoglobosin-ergosterol derivative hybrids. Compound 2 featured substitution at NH-1' and constituted the first example of this dimeric type bearing an R-configuration at C-3''. Compounds 3-5 were formed via a Diels-Alder cycloaddition between chaetoglobosins and 14-dehydroergosterol. Furthermore, it was revealed that compound 9-12 exhibited the significant cytotoxic activity against the human non-small cell lung cancer cell (A549), with compound 12 showing the most potent effect at an IC50 of 5.14 μM.
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