Cytotoxic Veraguamides, Alkynyl Bromide-Containing Cyclic Depsipeptides from the Marine Cyanobacterium cf. Oscillatoria margaritifera (original) (raw)

2011, Journal of Natural Products

13 b S Supporting Information 28 M arine cyanobacteria are exceptionally prolific producers of 29 structurally diverse secondary metabolites, of which many 30 have intriguing biological properties. 1 An emerging biosynthetic 31 theme in cyanobacterial natural products is the frequent combi-32 nation of polyketide synthase (PKS) and nonribosomal peptide 33 synthetase (NRPS) derived portions, and this results in a highly 34 diverse suite of nitrogen-rich structural frameworks, most of 35 which are lipid soluble. 2 A number of these cyanobacterial 36 metabolites possess terminal alkyne functionalites in the PKS-37 derived sections, including carmabin A, 3 georgamide, 4 pitipep-38 tolide A, 5 yanucamides, 6 antanapeptin, 7 trungapeptin A, 8 hantu-39 peptin, 9 wewakpeptins, 10 dragonamide, 11 and viridamide A. 12 40 Similar metabolites have also been obtained from several species 41 of mollusks, namely, Onchidium sp. and Dolabella auricularia, 42 yielding onchidins A 13a and B 13b and a family of kulolides, 14 43 respectively. Due to the strong and distinctive similarity between 44 these secondary metabolites isolated from mollusks and those of 45 cyanobacterial origin, it is highly likely that the mollusks obtain 46 these compounds from their diet of cyanobacteria. 47 Since 1998, the International Cooperative Biodiversity Group 48 (ICBG) in Panama, a program of the Fogarty International 49 Center of the National Institutes of Health, has enabled unique 50 opportunities to conduct integrated natural products investiga-51 tions, biodiversity inventories and conservation, infrastructure 52 development, and educational training. 15 Moreover, the country 53 of Panama permits the study of marine cyanobacteria from two 54 very different tropical environments, the Caribbean Sea in the 55 Western Atlantic and the Eastern Pacific. Some of these sites are 56 quite pristine and of exceptional biodiversity, such as Coiba 57 National Park (CNP), some 15 km off the Pacific coast of 58 Panama. CNP was formed in 2003 as a result of a developing 59 recognition of its high number of indigenous and endemic plant, 60 animal, and microbial species, and in 2005 it was named a World 61 Heritage Site by UNESCO. 16 62 Several filamentous tuft-forming species of marine cyanobac-63 teria were collected from CNP in 2010, and their extracts 64 evaluated in a number of biological assays. Two reduced com-65 plexity fractions from one extract, subsequently tentatively 66 identified as Oscillatoria margaritifera, were found to be highly ABSTRACT: A family of cancer cell cytotoxic cyclodepsipeptides, 15 veraguamides AÀC (1À3) and HÀL (4À8), were isolated from a 16 collection of cf. Oscillatoria margaritifera obtained from the Coiba 17 National Park, Panama, as part of the Panama International Co-18 operation Biodiversity Group program. The planar structure of 19 veraguamide A (1) was deduced by 2D NMR spectroscopy and 20 mass spectrometry, whereas the structures of 2À8 were mainly 21 determined by a combination of 1 H NMR and MS 2 /MS 3 techniques. 22 These new compounds are analogous to the mollusk-derived kulo-23