Tunicates compounds from

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]. 

Considerable effort has gone into investigating compounds from tunicates over the past two decades. For unknown reasons these chemicals are often potent antiviral agents, whereas clinicians have few drugs active against viruses. Didemnin B was the first of these candidate compounds to be examined and initially it showed promise against a broad spectrum of viruses. After lengthy clinical trials, however, it was finally abandoned as too toxic for safe human use. 

There are 34 fundamental phyla of life 17 occur on land and 32 in the sea (including some overlaps). More chemical diversity is found among marine hfe forms. Most of these are from invertebrate organisms— sponges, tunicates, and mollusks. Some of the compounds from marine life forms are extremely potent, given that these organisms have to defend themselves from attacks in vast volumes of water that dilute the compound. 

Pommier Y, Kohlagen G BaiUy C, Waring M, Mazumder A, Kohn K. (1996) DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry 35 13303-13309. 

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. 

Figure 6.7 Number of publications and pure compounds from tunicates (MarinLit 1951-2008). Orders 1. Aplousobranchia, 2. Enterogona, 3. Pleurogona...

Prof. Henri Braconot, director of Botanical Garden in Nancy [France] in 1811, first isolated a fibrous substance from the cell walls of mushroom, which he called FUNGINE. Later in 1823, Odier discovered that this compound is also one of the major constituents of the exoskeleton of insects and then he renamed as CHITIN [from Greek khiton meaning tunic or envelope). Prof. C. Rouget in 1859 prepared a compound from chitin by treatment with concentrated caustic solution and observed that, unlike chitin, the resulting substance dissolved in acids. This compound was then named CHITOSAN [pronounced as kite-o-san) by Hoppe-Seller In 1894 [1, 2]. 

Guan, Y., Sakai, R., Rinehart, K. L., Wang, A. H. J., 1993. Molecular and crystal structure s of ecteinascidins potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinata. J. Biomol Struct. Dyn. 10, 793-818. 

Ecteinascidins 729, 743, 745, 759A, 759B, and 770 potent antitumor agents from the Caribbean tunicate Ecteinascidia turbinata. (b) R. Sakai, K. L. Rinehart, Y. Guan, A. H. Wang, Pwc. Natl. Acad. Sci. U.S.A. 1992,89,11456-11460. Additional antitumor ecteinascidins from a Caribbean tunicate crystal structures and activities in vivo. For a review on antitumor compounds from tunicates, see (c) K. L. Rinehart, Med. Res. Rev. 2000, 20, 1-27. Antitumor compounds from tunicates. 

Chill, L., Rudi, A., Benayahu, Y., and Kashman, Y. (2004) Violatinctamine, a new heterocyclic compound from the marine tunicate Cystodytes cf. violatinctus. Tetrahedron Lett., 45, 7925-7928. 

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... 

The 4-aryl-2(5// )-furanone unit proved to be present in many naturally occurring (91JOC6275) and medicinally important compounds (93JHC1581). Examples are the potent antibiotics rubrolide A-F 90a-f, isolated by Miao and Andersen from the colonial tunicate Ritterela rubra (Scheme 26) (91JOC6275). 

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