Ascidians and sea hares: rich sources of Bioactive Natural Products

A survey of the metabolite content of fifty-two ascidians collected from New Zealandand Antarctica is presented. Using biological assays and reversed phase analytical C18 HPLCtechniques, twenty-three specimens were selected for further work. Work on ten of theselected ascidians is presented in this study. Using standard chromatographic techniquescombined with analytical C18 HPLC, eighteen metabolites were isolated of which sixteenexhibited biological activity. Ten of the eighteen metabolites were novel, with nine exhibitingbiological activity. The New Zealand endemic ascidian Pycnoclavella kottae, collected fromthe Three Kings Islands yielded the novel 2,2,5-trisubstituted imidazol-4-ones, kottamides A -D (3.1 - 3.4). Three new pyridoacridines (4.80, 4.82, 4.84), along with two knownpyridoacridines and the known benzopentathiepin, varacin were isolated from the NewZealand endemic ascidian Lissoclinum notti. Varacin was investigated for its use in ADEPTand a possible prodrug derivative was prepared. In addition, a novel biologically inactivepurine, 8-oxo-1,3-dimethylisoguanine (6.29) was isolated from the New Zealand endemicascidian Pseudodistoma cereum. The study of an ascidian of the genus Aplidium, collectedfrom the Ross Sea, Antarctica resulted in the isolation of two novel quinone derivatives,rossinones A (5.71) and B (5.72), which exhibited potent cytotoxicity and antiviral activity.Rossinones A (5.71 ) and B (5.72) provide insights into the biosyntheses of several terrestrialplant natural products.In addition, six sea hares of three species collected from the Auckland, New Zealandregion were surveyed using the same methodology, with three novel and seven knowncompounds being isolated. The study of the sea hare Aplysia dactylomela resulted in theisolation of two inactive novel tryptophan dipeptides, dactylamides A (7.9) and B (7.10), theknown ink pigment aplysioviolin and four known sesquiterpenes. A new malyngamide, S(8.8) along with an algal toxin, lyngbyatoxin A and its acetate were isolated from the sea hareBursatella leachii. A survey of nine algae collected from the same locations as the sea haresresulted in the identification of several of the dietary sources of these sea hares.Standard spectroscopic techniques were used for structural elucidation, including theuse of natural abundance 1H-15N 2-D NMR where required. All compounds were assayed fora range of biological activities.