Diterpenoid metabolites

Cronin G, Paul VJ, Hay ME, Fenical W (1997) Are tropical herbivores more resistant than temperate herbivores to seaweed chemical defenses Diterpenoid metabolites from Dictyota acutiloba as feeding deterrents for tropical versus temperate fishes and urchins. J Chem Ecol 23 289-302... 

Aphidicolin is a diterpenoid metabolite of Cephalosporium aphidicola and Phoma betae. The strueture of aphidieolin (5.126) was established in 1972 through a eombination of ehemieal, spectroseopie and X-ray crystallographic studies. Unlike the ent-kaurene and gibberellin metabolites of G. fujikuroi, aphidicolin possesses an absolute stereochemistry that is steroid-like . It has attracted considerable interest as a specific inhibitor of DNA polymerase a and as a potential anti-viral and anti-tumour agent. 

Paul, V.J. and Fenical, W. (1984) Novel bioactive diterpenoid metabolites from tropical marine algae of genus Halimeda (Chlorophyta). Tetrahedron, 40, 3053-3062. 

Francisco, C., Banaigs, B., Teste, )., and Cave, A. (1986a) Mediterraneols a novel biologically active class of rearranged diterpenoid metabolites from Cystoseira mediterranea (Pheophyta). J. Org. Chem., 51, 1115-1120. 

TRPV4 was identified a decade ago as an osmotransducer that is expressed in lung, heart, kidney, airway muscle cells, sensory neurons, brain, skin, gut, sympathetic nerves, inner ear, endothelium, and fat tissue [58-61]. TRPV4 is activated by heat (27-34°C), endogenous substances such as anandamide (59, AA) and the arachi-donic acid metabolite 5,6-epoxyeicosatrienoic acid (60, 5,6-EET), a plant dimeric diterpenoid bisandrographolide A (61, BAA), and the semisynthetic phorbol ester 4a-phorbol-12,13-didecanoate (62, 4a-PDD) [62],... 

The majority of natural products from tropical macroalgae are terpenoids (mainly sesqui- and diterpenoids), followed by acetogenins (acetate-derived compounds), and metabolites of mixed biosynthetic origin (such as meroditerpenes), frequently composed of terpenoid and aromatic portions (Blunt et al. 2007 and previous reviews see Chap. 1). 

Chlorophyta or green algae comprise one of the major groups of algae and include several exclusively marine orders and genera from tropical regions. Natural products chemistry research has identified more than 300 secondary metabolites from Chlorophyta, with most being sesquiterpenoid and diterpenoid compounds... 

Anionic oxy-Cope rearrangement was also employed for the enantioselective total synthesis of compounds related to marine metabolites (equation 230)305 307, as well as for the preparation of diterpenoide vinigrol (equation 231)308 and cerorubenic acid-in... 

The diterpenoid taxol (Figure 1.12) was first isolated from the pacific yew tree (Taxus brevifolia) in the late 1960s. Its complete structure was elucidated by 1971. Difficulties associated with the subsequent development of taxol as a useful drug mirror those encountered during the development of many plant-derived metabolites as drug products. Its low solubility made taxol difficult to formulate into a stable product, and its low natural abundance required large-scale extraction from its native source. 

The Mediterranean has also given peculiar triterpenes of squalene origin and an unusual cyclized cembranoid, coralloidolide C (Chart 7.5.A/I/PO). The latter resembles diterpenoids from tropical octocorals, indicating that these cnidarians, on migration to temperate waters, have conserved genes for secondary metabolites. 

Wide distribution also occurs in metabolites that play the same role in phylogenetically and ecologicafiy distant organisms, like peptides of the endothelin class (Chart 8.1.A/P), defensive monoterpenoids and steroids, the gibberellins (diterpenoid hormones) (Chart 8.1.1), and the alkaloid melatonin. 

Gorgonians produce the largest complement of chlorine-containing marine metabolites - more than 50 were illustrated in the first survey (7) - and many more nonchlorinated gorgonian diterpenes are known (665-667). There is evidence to indicate that these gorgonian diterpenoids are feeding deterrents to reef fishes. Gorgonian corals can achieve densities of up to 20 colonies per square meter on the reef (668, 669). 

New diterpenoids of the dolabellane class have been reported, such as clavinflol B (592) from the Taiwanese soft coral Clavularia inflata (706). This metabolite has comparable cytotoxicity against the KB cell line to doxorubicin. A sea whip of the genus Eunicea has yielded the cembrane 593 (707). Both 592 and 593 are considered to be natural since no chlorinated solvents were used in the isolation process, and in both metabolites the chlorine is attached to the less substituted carbon, opposite to what is expected for acid-induced epoxide ring opening. A Kenyan soft coral, Sinu-laria erecta, contains the norcembrane sinularectin (594) (708). 

The fungus Claviceps paspali Stevens et Hall elaborates a series of metabolites derived from indole and a diterpenoid unit. The structures of paspaline (5) and paspalicine (6) were proposed earlier, together with the partial stereochemistry of paspaline. These conclusions have now been confirmed, and the complete stereochemistry of paspaline and paspalicine has been elucidated, by X-ray... 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

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