Cembranoid diterpenes isolation

Sarcophyton species contain diterpenes up to 10% of their dry weight, and this large quantity of secondary metabolites plays an important role in the survival of Octo-corals with defensive, competitive, reproductive, and possibly pheromonal functions. Soft corals lacking physical defense thus seem to be protected from predation by the presence of diterpene toxins in their tissue. Nearly 25 species of this genus occurring in different seawaters have been examined chemically so far, and more than 80 cembranoid diterpenes have been isolated from the Sarcophyton genus since the 1970s. 

Chemical examination of Sarcophyton glaucum collected at Ishigaki island, Okinawa Prefecture, resulted in the isolation of seven cembranoid diterpenes, namely sarcophytol A (3), sarcophytol A acetate (4), sarcophytol B (5), sarcophy-tonin A (6), and minor constituents sarcophytol C (7), D (8), and E (9). These compounds were found to be susceptible to autooxidation while being purified. The structural determination of these compounds was made mainly based on proton and carbon nuclear magnetic resonance (NMR) spectral evidence and degradative studies by ozonolysis. X-ray crystallographic analysis for the two crystalline compounds, sarcophytol B (5) and D (8), has been reported. The total lipid extracts of S. glaucum comprise about 40% sarcophytol A (3), 5% each of sarcophytol A acetate (4) and sarcophytonin A (6), about 1% sarcophytol B (5), and minor amounts of sarcophytol C (7), D (8), and E (9). 

Again, soft corals and gorgonians are a rich source of diterpenoids of 19 structural classes, some of which are specific to them (35, 36). Besides tobacco plants, cembranoid diterpenes are limited to soft corals. Lophotoxin (126) isolated from sea whips of the genus Lophogorgia is a sodium channel inhibitor (3). Xenicin (127) from the soft coral Xenia elongata and briarein A (128) from the gorgonian Briareum asbestinum represent non-cembranolide diterpenes. Diterpenoids of these classes show antimicrobial, cytotoxic, and insecticidal activities. 

Bioassay-guided fractionation of an aqueous extract from a Philippine Islands collection of the soft coral Lohophytum spp. yielded cembranoid diterpenes, Fig. (3), which exhibited moderate HIV-inhibitory activity in a cell-based in vitro anti-HIV assay [44], while new isomalabaricane triterpenes. Fig. (4), have been isolated from the sponge Stelletta spp. [45]. Other anti-HIV diterpenes also included the dolabellane diterpenes isolated from the Brazilian brown algae Dictyota pfaffi [46] and Dictyota menstrualis [47]. To investigate the effect of these diterpenes in the reverse transcription of the viral genomic RNA, the recombinant HIV-1 RT was assayed in vitro in the presence of each compound. All compounds inhibited the RNA-dependent DNA-polymerase activity of HIV-1 RT and consequently virus replication. 

Cembranoids are present both in plants and animals. The majority of the cembranoids of plant origin was isolated from tobacco. Cembranoid diterpenes, which serve as a trail pheromone and defense secretions, have been obtained from termites Nasutitermes exitiosus [160], Trinervitermes bettonianus [161], and various species of Cubitermes [162] and the ant Monmorium pharaonis [163],... 

Cembranoids The first macrocyclic diterpene isolated from an Eremophila species was the triol (99) produced by E. clarkei (96). The resin obtained from this plant was a complex mixture of compounds from which the crystalline triol could be obtained with difficulty from the neutral fraction. Larger quantities of triol were available after methylation and lithium aluminium hydride reduction of the acidic fraction. The plane structure of 99 was established by conversion of the triol to a crystalline stereoisomer of cembrane (100) as shown in Scheme 25. The two dihydrotriols (101 and 102) obtained in this sequence also served to prove the location of the hydioxymethylene groups on the cembrane skeleton. Since both 101 and 102 are optically active, the symmetrical 4,12-cis arrangement of the primary alcohol groups can be excluded. Furthermore, the 4, 2-trans-disposition of these groups can also be excluded since elimination of the asymmetry at Cl leads to two different olefins (103 and 104). 

Cembranes, cembranoids monocyclic diterpenes isolated from several plants, in particular from the gum resins of pines. C. have also been found in marine coelenterates and insects. 

Fontan, L.A. and Rodriguez, A.D. (1991) Isolation of eupahnerin, a nor cembranoid diterpene from the Caribbean gorgonian Eunicea mammosa. J. Nat. Prod., 54, 298-301. 

Sanduja, R., Linz, G.S., Alam, M., Weinheimer, A.J., Martin, G.E., and Ezell, E.L. (1986a) 2D-NMR studies of marine natural products. IV. Isolation of the cembranoid diterpene jeunidn from the mollusc Plamxis sulcatus assignment of the H and NMR./. Heterocycl. Chem., 23, 529-535. 

Wasylyk, J.M. and Alam, M. (1989) Isolation and identification of a new cembranoid diterpene from the tunicate Styela plicata. J. Nat. Prod., 52,1360-1362. 

Cembranoids, a macrocylic class of diterpene hydrocarbon were first isolated from pine oleoresins [156, 157] and the tobacco plant [158]. Since then, the structures of circa 300 naturally occurring cembranoids have been elucidated and a comprehensive compilation of these diterpenes published through 1990 has been published [159]. Known cembranoids include both hydrocarbons and oxygen-containing compounds such as epoxy, oxo, hydroxy, and lactone functions. Most congeners are polyoxygenated. 

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