Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B-E (1-4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1-4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1-4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B-D (1-3) showed moderate or no cytotoxic effects.
cycloaromatization, cyclopenta[a]indene, enediyne, jejucarboside, marine actinomycete
NCBI PubMed ID: 37504936Publication DOI: 10.3390/md21070405Journal NLM ID: 101213729Publisher: Basel, Switzerland: Molecular Diversity Preservation International
Correspondence: D.C. Oh
Institutions: Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Methods: 13C NMR, NMR-2D, FTIR, UV, extraction, optical rotation measurement, CD, HR-ESI-MS, H NMR, cytotoxicity assay, LR-ESI-MS, reverse-phase HPLC
Found