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.