Trididemnum solidum

The majority of promising drug candidates emerging from marine natural products research to date are potential cancer treatments. Six anti-cancer compounds that are either marine natural products or synthetic analogs of marine natural products have made it to clinical trials. The first of these compounds to enter clinical trials was didemnin B (43), one of a family of cyclic depsipetides isolated from the Caribbean tunicate Trididemnum solidum Didemnin B was advanced to Phase II clinical trials for treatment of small cell lung cancer, myeloma, prostate cancer, and melanoma. Unfortunately, no favorable responses were found so the compound has been withdrawn. Crude extracts of another Caribbean tunicate, Ecteinascidia turbinata, showed extremely... 

Nickel exists in the tunicate Trididemnum solidum as the nickel complex of a modified chlorin (Bible et al. 1988) and is a component of a number of enzymes. Urease is the classic example of a nickel-containing enzyme, and several enzymes contain both nickel and iron. Details of enzymes that contain nickel have been provided in a review (Mulrooney and Hausinger 2003), and only brief summaries are provided ... 

Bible KC, M Buytendorp, PD Zierath, KL Rinehart (1988) Tunichlorin a nickel chlorin isolated from the Caribbean tunicate Trididemnum solidum. Proc Natl Acad Sci USA 85 4582-4586. 

Larvae of the tunicate Trididemnum solidum are most likely protected by didemnins like 44-46, cyclic depsipeptides that were initially identified from adults of this species [92]. The larvae are highly unpalatable to the wrasse Thalassoma bifasciatum, which rejected the larvae while readily consuming krill eyes that served as larval mimics. Coating one krill eye with the lipid soluble compounds from a single T. solidum larva rendered it as unpalatable as the larvae themselves. Reduced feeding was also observed when didemnin B (45) and nor-didemnin B (46) were administered to reef fishes in the field (Scheme 12) [92]. 

Scheme 12 Didemnins from the tunicate Trididemnum solidum...

Rinehart, K.L., Jr. Kishore, V. Bible, K.C. Sakai, R. Sullins, D. Li, K.-M. (1988) Didemnins and tunichlorin novel natural products from the marine tunicate Trididemnum solidum. J. Nat. Prod., 57,1-21. 

A highly unusual porphynoid (117), named tunichlorin, was isolated from the Caribbean tunicate Trididemnum solidum from which didemnins (Section VIII), anticancer cyclopeptides, had previously been obtained... 

Didemnin B (347) is a cyclic depsipeptide isolated from the Caribbean tunicate Trididemnum solidum and is currently in phase II clinical trials as an anticancer agent. Didemnin B also shows antiviral and immunosuppressive activity. The structure of didemnin B was revised to 347 containing... 

Importantly, Lindquist et al.53 also document that ascidians can exhibit chemical differences between defensive secondary metabolites among adults and larvae. For example, larvae from colonies of Sigillina cf. signifera contained more tambjamine C, less tambjamine E, and no tambjamine F as compared to adults.65 Moreover, larvae of Trididemnum solidum contain only four of the six didemnins found in adults.53 This could be the result of different selective pressures during planktonic vs. benthic life history phases. In contrast, Lucas et al.44 found no differences in the saponin chemical defenses of the embryos, larvae, and adults of the sea star Acanthaster planci. Clearly, additional studies are needed to expand the evaluation of ontogenetic shifts in defensive chemistry in marine organisms. 

In yet another study focusing on the larvae of a colonial ascidian, Lindquist and Hay71 evaluated not only whether secondary metabolites in the large brooded larvae of Trididemnum solidum cause... 

The Caribbean tunicate Trididemnum solidum and its larvae contain a complex mixture of didemnin/ nordidemnin metabolites that act as feeding deterrents in field-based assays at below natural concentrations. The most potent metabolite is nordidemnin B 147.28 Crude extract mixtures enriched in didemnin B 148 induce vomiting in the spotted pinfish L. rhomboides, causing these fish to avoid feeding.173 The larvae of other didemnid ascidians are also protected by the presence of deterrent chemicals.28 174... 

Didemnins were isolated from a Caribbean tunicate Trididemnum solidum. These structurally unique cyclic depsipeptides have quite interesting cytotoxic, antiviral, and immunosuppressive activities. The synthesis of the didemnins A, B, and C (173-175) involves the key component 178, which is prepared from acid 176 and amine 177 using the coupling agent DEPC.69... 

The didemnins are cyclic molecules composed of amino acids that were isolated from the marine invertebrate Trididemnum solidum. One of the amino acids is proline. The didemnins exhibit antitumor, antiviral, and i m m u n osu ppressi ve activity. The group labeled "R" in the structure is a side chain that contains additional amino acids. 

The nickel containing tunichlorin (57) and its derivatives (58-60) were discovered in the tunicate Trididemnum solidum which occurs in the Carribean Sea (35). Structural elucidation was carried out by UV/Vis, CD, MS, and NMR spectroscopy on dimethyltunichlorin (58), which was prepared by etherification of the 3-hydroxymethyl group and esterification of the 17-propionic acid side chain. 

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