Jejucarbosides B–E, Chlorinated Cycloaromatized Enediynes, from a Marine Streptomyces sp.

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 IC(50) 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.