Marine tunicate metabolite

Unlike carbazoles, haiogenated (3-carbolines are abundant in nature [1[. For example, the simple eudistomin O (7-bromo-(3-carboline) (40) is a ubiquitous marine ascidian metabolite [44[. Indeed, the tunicate genus Eudistoma has furnished most of the extant haiogenated (3-carbolines, some of which have significant antiviral (polio, herpes) and microbial activity. The Caribbean Eudistoma olivaceum produces at least 15 brominated carbolines [1[. A study of Eudistoma gilboverde uncovered the new eudistomins 41-43[45[, and the Australian ascidian Pseudodistoma aureum has... 

Much interest and research over the past 15 or so years has been directed towards ascidian metabolites because of the high incidence of pharmacological activity that they display. Few comprehensive reviews exist on the topic the only general ones being those produced by Davidson in 1993 [1,2] and the Marine Natural Product literature reviews by Faulkner which always contain a section on tunicate metabolites [3-13]. Although a number of non-nitrogenous metabolites have been isolated from the tunicates, the majority of compoimds isolated have been derived from amino acids. In particular, the two most commonly encountered classes are cyclic peptides and polycyclic aromatic alkaloids. 

A number of metabolites which appear to be derived from Tyrosine, Dopa, or Topa residues and to have similar biogenetic origins to the tunichromes have been reported. Rigidin (48), isolated from the Okinawan marine tunicate Eudistoma c.f. rigida exhibited calmodulin antagonistic activity with an IC50 of 5 x lO M against calmodulin-activated brain phosphodiesterase [42]. Some other pyrrolo[2,3d]pyrimidine-2,4-diones which have been synthesised have shown weak affinity for the benzodiazepine receptor. 

Hogan, I.T., and M. Sainsbury The Synthesis of Dendrodoine, 5-[3-(N,N-Dimeth-ylamino)-l,2,4-thiadiazolyl]-3-indolylmethanone, a Metabolite of the Marine Tunicate Dendroda grossular. Tetrahedron 40, 681 (1984). 

Rudi, A., Benayahu, Y, Goldberg, 1., and Kashman, Y. (1988b) Alkaloid metabolites of the marine tunicate Eudistoma sp. segoline A, isosegoline A and nor-segoline. Tetrahedron Lett., 29,3861-3862. 

Most of the marine metabolites bearing a sulfide group correspond to well-defined families of alkaloid compounds and they have mainly been obtained from tunicates and sponges. To a lesser extent they have also been found in bryozoans, molluscs, and algae. 

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

Finally, a symbiotic origin was suggested for these metabolites since the pyrroloquinoline skeleton has been found in marine natural products obtained from different sources, mainly tunicates and sponges [60]. 

Tunicates are by far the most important source of marine metabolites containing disulfides and polysulfides, followed in importance by marine microorganisms and, to a lesser extent, sponges and algae. 

The marine isothiocyanates, with more than 80 compounds isolated so far, form the largest group of naturally occurring isothiocyanates. This well-established group of marine natural products is constituted mainly by terpene metabolites present as sesquiterpene and diterpene derivatives. The non-terpene isothiocyanate compounds include two cylindricine alkaloids and a series of long-chain aliphatic metabolites. Marine sponges constitute the main source of these compounds, although they are also found in nudibranches and tunicates. 

The thiazoline and thiazole rings are present in many cyclic peptides isolated from marine organisms. Most of these types of compound have been isolated from tunicates belonging to the Lissoclinum and Didemnum genus, from sponges of the genus Theonella, and from the sea hare mollusc Dolabella auricularia. The isolation of closely related compounds from cyanobacteria pointed out the symbiont origin of these metabolites. 

Other miscellanous thiazole-containing metabolites were obtained from a variety of marine organisms. Compounds 448 and 449 were isolated from the tunicate Aplidium pliciferum and their structures were established from spectral data and confirmed by synthesis [349]. Very few secondary metabolites have been reported from hydroids. The thiazole tridentatol C... 

The peptide guanidine derivatives minalemines D-F (459-461), isolated from the New Caledonian tunicate Didemnum rodriguesi, were the first marine metabolites containing a sulfamic acid functional group [354]. Their structures were elucidated through their spectral data and by chemical transformations. 

Several partially characterized inhibitors have been described from the marine bacterium Pseudoalteromonas tunicata, isolated from the tunicate Ciona intestinalis. This bacterium produces a diversity of metabolites, each of which specifically inhibits the settlement of invertebrate larvae... 

Bis(indolyl)alkanes and their derivatives constitute an important part of bioactive metabolites both synthetic and natural terrestrial and marine origins [169-174], Bioactive bis(indolyl)ethylamines 224-226 have recently been reported from marine sources, such as a tunicate and a sponge (Scheme 50) [169-173]. There are a few synthetic methods for synthesis of bis(indolyl)ethylamines [175,176]. But methods are materializing with either strong reaction conditions or in very low or wide ranging yields. 

Lamellarins were originally extracted from a marine prosobranch mollusk Lamdlaria sp. and subsequently from primitive chordate ascidians (tunicates) [23]. These ascidian species, knovm to produce many bioactive metabolites, likely represent the original producer of lamellarins because these organisms are presumed to be the dietary source of the Lamdlaria mollusks. Lamellarins have been isolated from different tunicates, including recently from the Indian ascidian Didemnum obscurum... 

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