Theonellamides J and K and 5- cis -Apoa-theopalauamide, Bicyclic Glycopeptides of the Red Sea Sponge Theonella swinhoei

is a fairly common inhabitant of reefs throughout the Indian and Pacific Oceans. Metabolomic analyses of samples of collected in different depths in the Gulf of Aqaba revealed two chemotypes differing in the profiles of the theonellamides they produce, some of which seem to be unknown. Driven by this finding, we examined a sample of collected more than 40 years ago in the southern part of the Gulf of Aqaba. Large-scale extract of this sample yielded four theonellamides, the known theopalauamide ( ), as the major component, and three new metabolites, theonellamide J ( ), 5- -Apoa-theopalauamide ( ), and theonellamide K ( ), as the minor components. The planar structure of these complex cyclic glycopeptides was elucidated by combination of 1D and 2D NMR techniques and HRESIMS. The absolute configuration of the amino acids was established by Marfey's and advanced Marfey's methods, and the absolute configuration of its galactose unit using "Tanaka's method" for monosaccharides. The biological activity of the pure compounds was tested for antibacterial activity and for cytotoxicity to HTC-116 cell line. The compounds presented significant cytotoxicity against the HTC-116 cell line, illuminating the importance of the Apoa subunit for the activity.