Amphimedon

The biosynthesis of pregnenelone (112) in mammals has been well documented [1] it is known to be produced from cholesterol (1) via its 20,22-dihydroxy derivative (121) (Scheme 19A). The origin of 112 has been investigated in the sponge Amphimedon compressa. At the present time it is not known whether cholesterol and its 20,22-dihydroxy derivative serve as precursors for this pregnane in A. compressa however a new pathway (Scheme 19B) has been found to operate [89]. This involves the conversion of 22-dehydro sterols (e.g. stigmasterol, 122) to pregnenelone. The mechanism is believed to... 

Shortly after amphilectanes 96 and 97 were reported, other metabolites from Amphimedon were isolated, with the majority of their structures supported by the corresponding spectral and X-ray data. Although the gross structures of the series, 98-100, are regio isomers with respect to one of the isocyano functions, they also exhibit minor differences in the C4 moiety attached to C-l. X-ray determination of 98 led to assignment of its relative stereochemistry, thereby securing assignments for 99 and 100 by comparison of spectroscopic data [61]. 

The 7,15-diisocyano isomer (101) of 95 (-NC substituents at C-7 and -20), and 8-isocyano-10-cycloamphilectene (102) are also Amphimedon metabolites. 

Fatty acids arnnhimic acids (Amphimedon sp., Haplosclerida, Porif. from GBR Nemoto 1997). 

Alkylpyridines supposedly lie also along another biosynthetic route, affording pofymeric pyridinium compounds in marine haliclonid sponges the Indo-Pacific Callyspongia fibrosa (Davies-Coleman 1993), the Caribbean Amphimedon compressa (Albrizio 1995), and the Mediterranean Reniera sarai (Sep5i6 1997). 

Tsuda, M. Hirano, K. Kubota, T. Kobayashi, J. (1999A)Pyrinodermin A, a cytotoxic pyridine alkaloid with an isoxazolidine moiety from sponge Amphimedon sp. Tetrahedron Lett., 40, 4819-20. 

Fused tetracyclic and pentacyclic alkaloids constitute a relatively new class of natural products isolated mostly from ascidians and sponges. Cytotoxic, antimicrobial and antiviral activities have been reported for many of these compounds. The manzamine alkaloids, Fig. (33) are characterized by a complex pentacyclic diamine linked to C-l of P-carboline moiety. Manzamine have been isolated mainly from six different genera of marine sponges Haliclona, Pellina, Xestospongia, Ircinia, Pachypellin and Amphimedon. 

Manzamine-type alkaloids were also reported in another samples of marine sponges, eg., the Okinawan Amphimedon sp. [252-254], Pachypellina sp. [255], and a novel alkaloid called hyrtiomanzamine from Hyrtios erecta, with interesting immunosuppressive activity [256]. From... 

Garson MJ, Zimmermann MP, Hoberg M, Larsen RM, Battershill CN, Murphy PT (1993) Isolation of Brominated Long-Chain Fatty Acids from the Phospholipids of the Tropical Marine Sponge Amphimedon terpenensis. Lipids 28 1011... 

Fused tetra- and pentacyclic aromatic alkaloids are a new, emerging group of compounds from marine organisms. Amphimedine (187) was isolated from a Pacific sponge (Amphimedon sp.) as a cytotoxic compound in 1983 and was the first example of a polycyclic alkaloid (158). A pigment from the sea anemone Calliactis parasitica, named calliactine, has been known for many years, but the structure elucidation of calliactine was a difficult problem (159). In 1987 the structure of calliactine was proposed to be 188 on the basis of modern spectroscopic methods as well as chemical... 

Garson, M. J., Biosynthesis of the novel diterpene isonitrile diisocyanoadociane by a marine sponge of the Amphimedon genus incorporation studies with [14C]cyanide and sodium [2-14C]acetate, J. Chem. Soc. Chem. Commun., 35, 1986. 

Fookes, C. J. R., Garson, M. J., MacLeod, J. K., Skelton, B. W., and White, A. H., Biosynthesis of diisocyanoadociane, a novel diterpene from the marine sponge Amphimedon sp. Crystal structure of a monoamide derivative, J. Chem. Soc. Perkin Trans. I, 1003, 1988. 

Simpson, J. S. and Garson, M. J., Advanced precursors in marine biosynthetic study The biosynthesis of diisocyanoadociane in Amphimedon terpenensis, Tetrahedron Lett., 40, 3909, 1999. 

Garson, M. J., Thompson, J. E., Larsen, R. M., Battershill, C. N., Murphy, P. T., and Berquist, P. R., Terpenes in sponge cell membranes cell separation and membrane fractionation studies with the tropical marine sponge Amphimedon sp., Lipids, 27, 378, 1992. 

For the structurally more complex molecule 18, only the Schrock conditions worked. Compound 18 has been synthesized as a synthetic precursor of the marine alkaloid nakado-marin A (19 [14]) from the marine sponge Amphimedon sp. Nakadomarin A (19) belongs to the manzamine alkaloids, which are also targets of biomimetic syntheses [15], For both strategies, there is still some distance to go. 

Hydroxymanzamine A was isolated from the Indonesian sponge PachypeUina sp. with moderate antitumor and anti-HSV-II activity, in 1994 ]39]. It was named as manzamine Gin some literature ]20]. 6-Hydroxymanzamine A (called manzamine Y in some references [20,41]) and 3,4-dihydromanzamine A were isolated from the Okinawan marine sponge Amphimedon sp. The Philippine sponge Xestospongia (=Acanthostrongylophora) ashmorica Hooper yielded manzamine A N-oxide, 3,4-dihydromanzamine A N-oxide, and 6-deoxymanzamine X ]10]. 

In a continued search for new manzamine alkaloids, 1,2,3,4-tetrahydromanza-mine B (35) and ma eganedin A (36) has been isolated from the same species of the Okinawan marine sponge Amphimedon sp. [45,51]. Ma eganedin A has a unique methylene carbon bridge between N-2 and N-27. Their stmctures, including the absolute configuration, were elucidated from spectroscopic data. 

Dihydromanzamine J (37) was isolated from the Okinawan marine sponge Amphimedon sp. along with manzamine M and 3,4-dihydro-6-hydroxymanzamine A [40]. Manzamine J N-oxide was obtained from the Philippine sponge Xestospongia... 

Manzamine C (40) is characterized by a 2-ethyl-N-azacycloundec-6-ene connected to C-1 of a p-carboline. To date, only two analogs of this type of manzamine have been reported. Manzamine C was obtained from the same species Haliclona sp. that yields manzamine A [37a[. Keramamine C (41) was isolated from an Okinawan marine sponge Amphimedon sp. [18[. 

Keramaphidin C (50) was isolated from sponge Amphimedon sp. [18]. Haliclorensin (51) was isolated from Halidona sp. and its structure was first proposed as 51 [54]. However, the synthetic ( )-51, (R)- and (S)-51 showed significant differences in NMR and mass spectra from those of natural halicloresin [55]. The structure ofhaliclorensin was revised to (S)-7-methyl-l,5-diazacydo-tetradecane (51a) recently [56]. 

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