Marine tunicate

Kobayashi J, Cheng JF, Ohta T Nozoe S, Ohizumi Y, Sasaki T, Eudistomidins B, C, and D Novel antileukemic alkaloids from the Okinawan marine tunicate Eudistoma glaucus, J Org Chem 55 3666—3670, 1990. 

Isocyanide-based MCR was also applied for the total synthesis studies of natural products containing piperazine substructure. For example, trabectedin (also known as ecteinascidin 743 or ET-743) is undergoing clinical trials for the treatment of breast, prostate, and pediatric sarcomas. Ecteinascidin 743 (2) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinate [12]. Eukuyama et al. developed the total synthesis of ecteinascidin 743 from a Ugi reaction [13]. The reaction of p-methoxyphenyl isocyanide 3 gave Ugi product 7, which was cyclized to DKP intermediate 8 (Scheme 1). 

Thiadiazole (1) was first prepared and characterized in 1955 but products containing this ring system were described as early as 1821. A natural product containing the 1,2,4-thiadiazole nucleus was not reported until 1980. Dendrodoine (2) is a cytotoxic material isolated from the marine tunicate Dendrodoa grassularia <84CHEC-I(6)463>. 

Chbani, M. Pals, M. Delauneux, J.M. Debitus, C. (1993) Brominated indole alkaloids from the marine tunicate Pseudodistoma arborescens. J. Nat. Prod., 56,99-104. 

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. 

Figure 16-27 (A) Structure of the nickel-containing prosthetic group F430 as isolated in the esterified (methylated) form. From Pfaltz et al.i59 The "front" face, which reacts with methyl-coenzyme M, is toward the reader.458 (B) Structure of a representative member of a family of tunichlorins isolated from marine tunicates.460 For tunichlorin R = R = H. Related compounds have R = CH3 and/or R = an alkyl group with 13-21 carbon atoms and up to six double bonds.

Marine tunicates are a rich source of intriguing structures and interesting biological activities. Eudistomidin A (1) from the Okinawan tunicate Eudistoma glaucus possesses powerful calmodulin antagonistic activity (IC5o 3 x 10 M). Eudistomidins B-D (2-4) show potent cytotoxicity... 

Marine tunicates are also a source of brominated tyrosine derivatives. The colonial ascidian Aplidium sp., which was collected in Australia, yielded the novel iodinated tyrosine alkaloids 1973-1975 (1819). Collections of Botryllus sp. and Botryllus schlosseri from the Philippines and the Great Barrier Reef, respectively, have afforded botryllamides A-D (1976-1979) (1820). A Palauan ascidian Botrylloides tyreum produces several new botryllamides, including the brominated botryllamide G (1980) (1821). The simple brominated tyramines 1981 and 1982 were isolated from the New Zealand ascidian Cnemidocarpa bicornuta (1822) and an Indonesian Eudistoma sp. ascidian (1823). 

Sato H, Tsuda M, Watanabe K, Kobayashi J (1998) Rhopaladins A-D, New Indole Alkaloids from Marine Tunicate Rhopalaea sp. Tetrahedron 54 8687... 

Reyes F, Fernandez R, Rodriguez A, Francesch A, Taboada S, Avila C, Cuevas C (2008) Aplicyanins A-F, New Cytotoxic Bromoindole Derivatives from the Marine Tunicate Aplidium cyaneum. Tetrahedron 64 5119... 

Ecteinascidin 743 262 (Scheme 12.37) represents a powerful antitumor agent, which has been submitted to clinical trial. This complex polyazacydic, polyaromatic compound was isolated from the marine tunicate, Ecteinascidia turbinate [131]. A total synthesis of this natural product, which featured an Ugi four-component reaction as pivotal step, was recently reported by Fukuyama and co-workers [132]. The highly decorated phenylglycinol 263 was obtained via an asymmetric Mannich-type reaction [133], and was engaged in a multicomponent condensation process involving the protected amino acid 264, p-methoxyphenyl isocyanide 265 and acetaldehyde to afford dipeptide 266 in high yield. This com-... 

Kerr, R. G. and Miranda, N. L., Biosynthetic studies of ecteinascidins in the marine tunicate Ectein-ascidia turbinata, J. Nat. Prod., 58, 1618, 1995. 

The color of our synthetic material was a deep yellow, A.max (e) 352 (14110). The reported color of naturally isolated rigidin was described as purple and revealed an extra absorption at A.max of401 (2500) (Ref. 11). We believe this to be ascribable to a colored impurity co-isolated from the marine tunicate. 

Nonnucleoside compounds which have been fully characterized include rigidin, from the marine tunicate Eudistoma cf. rigida <90TL4617> and echiguanines A and B from Streptomyces sp. <91MI 707-03). 

Two cyclic peptides that were isolated from the marine tunicate Lissoclinum patella,30 named ulicyclamide and ulithiacyclamide, have structures (33) and (34). 

Ecteinascidin-743 (ET-743, 16, Figure 2.4) is a tetrahydroisoquinolone alkaloid isolated from Ecteinascidia turbinata Herdman, a tunicate that grows on mangrove roots throughout the Caribbean Sea [154]. Most likely, the compound is produced by the marine tunicate as a defense mechanism to survive in its natural environment [155]. 

Disubstituted indolizidines, unlike many classes of amphibian alkaloids, are not unique to amphibians. 3,5-Disubstituted indolizidines such as monomorine I [(5Z,9Z)-195B] occur in ants of the genera Monomorium and Solenopsis (125,129,134). Some of the ant indolizidines are as follows (5Z,9Z)-3-n-butyl-5-methylindolizidine (monomorine I), (5Z,9Z)-3- -ethyl-5-methylindolizidine, (5Z,9Z)-3-hexyl-5-methylindolizidine, and (5 ,9Z)-3-butyl-5-(4-pentenyl)indolizidine. A series of 5-substituted indolizidines, the piclavines, were reported recently from a marine tunicate (Clavelina picta) (135). 

Ecteinascidin 743 is a potent antitumor agent that was isolated from a marine tunicate. T. Fukuyama et al. applied the intramolecular Heck reaction as the key step in the assembly of the central bicyclo[3.3.1] ring system.Toward this end, the cyclic enamide precursor was exposed to 5 mol% of palladium catalyst and 20 mol% of a phosphine ligand in refluxing acetonitrile to afford the desired tricyclic intermediate in 83% isolated yield. 

Ecteinascidin 743 is an extremely potent antitumor agent isolated from a marine tunicate. The total synthesis of this natural product was realized in the laboratory of T. Fukuyama." To achieve the synthesis of the key dipeptide fragment, they utilized the Ugi four-component reaction. The transformation was carried out under mild conditions providing the product with excellent yield. 

A review describes the pharmacological properties of l,2-benzisothiazoles. In connection with thiazoles, we find several reviews or papers thiazoles in food aromas patellamides, which are antineoplastic cyclic peptides, from the marine tunicate Lissoclinum patella, which contain an unusual fused oxazoline-thiazole unit and polythiazole-containing peptide antibiotics. An interesting total synthesis of the aglycon of bleomycin A2 should also be mentioned. ... 

Krenisky, J. The Biosynthetic Production of Marine-Derived Antitumor Ecteinascidins and the Aquaculture of the Marine Tunicate Ecteinascidia turbinata,... 

Miranda, N. Biosynthetic Studies of the Antitumor Ecteinascidins in the Marine Tunicate Ecteinascidia turbinata. M.S. Thesis, Florida Atlantic University, 1996. 

The phenomenon described above, that is, that related compounds were obtained from marine tunicates, sponges, and terrestrial bacteria, was also observed in the following compounds of the haterumalide series. From an Okinawan ascidian Lis-soclinum sp., a cytotoxic chlorinated 14-membered macrolide, haterumalide B... 

Corley, D. G., Moore, R. E., and Paul, V. J. (1988). Patellazole B A novel cytotoxic thiazole-containing macrolide from the marine tunicate Lissoclinum patella. J. Am. Chem. Soc. 110, 7920-7922. 

Kikuchi, Y., Ishibashi, M., Sasaki, T., and Kobayashi, J. (1991). lejimalides C and D, new anti-neoplastic 24-membered macrolide sulfates from the Okinawan marine tunicate Eudistoma cf. rigida. Tetrahedron Lett. 32,797-798. 

Heptyl prodigiosin (43) [Fig. (13)] is another antimalarial alkaloid isolated from a tunicate. Precisely, this pigment was purified from a culture of a-proteobacteria isolated from a marine tunicate and showed an antimalarial activity similar to that of quinine against the chloroquine -sensitive strain P. falciparum 3D7 with an in vitro activity that was about 20 times the in vitro cytotoxic activity against mouse lymphocytes. When this molecule was tested in vivo, a single administration of 5 mg/Kg significantly extended the survival of P. berghei ANKA strain-infected mice but, unfortunately, the same dose caused sclerotic lesions at the site of injection [62],... 

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