Didemnum

Steglich s group coupled A-methyl bromoindolylmaleimide 36 with 5-tributylstannyl-l-methyl-1//-imidazole to afford 37 and then converted 37 to didemnimide C (38), an alkaloid isolated from the Caribbean ascidian Didemnum conchyliatum [25]. 5-Tributylstannyl- 1-methyl-IH-imidazole, in turn, was prepared according to Undheim s direct metalation method from 1-methyl- l/Z-imidazole [26]. 

Hyella caespitosa Bron et Flah Tedania ignis Nostoc sphaericum Tolypothrix tjipanasensis New Zealand Ascidian Australian Ascidian Didemnum sp. 

Eour years later, Kang and Eenical reported the isolation of ningalin D (282) from a marine ascidian of the genus Didemnum collected in Western Australia, near Ningaloo Reef. On the basis of the restricted rotation and also because of the apparent helicity, 282 could be chiral. However, from the marine source, it was available only in racemic form (248). 

Cyclohexapept bistratamides Lissoclinum spp., Didemnidae, Ascid. from GBR and the Philippines Foster, 1992) comoramides Didemnum molle, Didemnidae from Comoro Is Rudi 1998) Oiexalpatellins Lissoclinum sp. from Fiji Is. Carroll 1996). 

Carroll, A.R. Bowden, B.F. Coll, J.C. Hockless, D.C.R. Skelton, B.W. White, A.H. (1994) Mollamide, a cytotoxic cyclic heptapeptide from the compound ascidian Didemnum molle. Aust. J. Chem., 47,61-69. 

Davis, R.A. Carroll, A.R. Pierens, G.K. Quinn, R.J. (1999A)New lamellarin alkaloids from the Australian ascidian, Didemnum chartaceum. J. Nat. Prod., 62, 419-24. 

Rudi, A. Aknin, M. Gaydou, E.M. Kashman, Y. (1998) Four new cytotoxic cyclic hexa- and heptapq>tides from the marine ascidian Didemnum molle. Tetrahedron, 54, 13203-10. 

Vervoort, H.C. Fenical, W. Keifer, P.A. (1999) A cyclized didemnimide alkaloid from the Caribbean ascidian Didemnum conchyliatum. J. Nat. Prod., 62,389-91. 

Riccio, R., Kinnel, R. B., Bifulco, G., and Scheuer, P. J. (1996). Kakelokelose a sulfated mannose polysaccharide with anti-HIV activity from the Pacific tunicate didemnum molle. Tetrahedron Lett. 37,1979-1982. 

A number of cyclic peptides have been isolated from the tunicate Didemnum molle. The structure of mollamide (59), a cytotoxic heptapeptide isolated from Didemnum molle from the Great Barrier Reef, was determined by X-ray crystallography and chemical degradation [88]. Mollamide has also been synthesised [89]. 

A Didemnum sp. from Palau was the source of didemnaketal C (65), which contains a sulfonic acid group [95]. The in vitro anti-human immuodeficiency virus (anti-HTV) activity of D. molle from Pohnpei is associated with the sulfated mannose polysaccharide kakelokelose (66) [96],... 

Lamellarin T-V and Y sulfates (67-70) were isolated from an unidentified ascidian from the Arabian Sea coast of India [97]. Four additional lamellarin sulfates, the 20-sulfates of lamellarins B, C and L and lamellarin G 8-sulfate (71-74) were isolated from Didemnum chartaceum from the Great Barrier Reef [98]. Unusually long relaxation times were observed for certain signals in the H NMR spectra of these compounds. Lamellarin a 20-sulfate (75) was isolated from an unidentified ascidian from India and was an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase [99]. 

Didemnum rodriguesi from New Caledonia contained the unusual peptidyl alkaloid caledonin (76), that formed a complex with Zn2+ and Cu+ ions between thiol and primary amine groups [100], The minalemines D-F (77-79) are peptide guanidine derivatives isolated from a Caribbean collection of D. rodriguesi and contain a sulfamic acid group [101]. The stereochemistry of cyclodidemniserinol trisulfate (80) from a Palauan specimen of Didemnum guttatum was partially determined [102]. 

A Didemnum sp. from Rota in the northern Mariana Islands contained four new (3-carboline alkaloids, didemnolines A-D (95-98), together with known metabolites [119]. The didemnolines are characterised by substitution at N9 as opposed to Cl. A straightforward synthesis of the didemnolines was reported [120],... 

Didemnolines A (31) and C (32) from the marine ascidian Didemnum sp. are cytotoxic to human epidermoid carcinoma KB cells (IC5o values of 6.1 and 0.28 pg/ml, respectively) and antimicrobial toward Staphylococcus aureus, Bacillus subtilis, and Escherichia coli [44,45]. 

Didemnimides B (219) and D (220) have been isolated from the Caribbean mangrove ascidian Didemnum conchyliatum [170]. 

The didemnolines A-D (30-33) isolated from the tunicate Didemnum sp. represent an additional family of P-carboline metabolites [33]. They differ from the other derived P-carboline compounds in that they are substituted at the N9 position rather than at the C-l position. All of these compounds showed moderate cytotoxic activity against KB cells, with the sulfoxide-containing compound, didemnoline C (32), being the most active with an IC50 value of 0.28 pg/ml. Compounds 30 and 32 also exhibited... 

Finally, the sulfonic acid group can also be found into an isoethionic acid portion in didemnaketal C (337), isolated from the Palauan tunicate Didemnum sp. [252]. The authors suggested that the previously reported metabolites isolated from this source are actually artifacts of 337 resulting from prolonged storage in methanol at 4 °C. 

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. 

Another tunicate, Didemnum molle, has been shown to contain a novel series of cyclic peptides. They include the hexapeptides comoramides A (391) and B (392) [301] and the heptapeptides, mollamide (393) [302], cyclodidemnamide (394) [303], and mayotamides A (395) and B (396) [301]. The structures of these compounds were elucidated from spectral data, degradation experiments and, in the case of mollamide (393), by X-ray analysis. The total synthesis of cyclodidemnamide led to the revision of its structure [304]. All of them exhibited cytotoxic activity and 393 also inhibited RNA synthesis [302]. 

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. 

Kiyota, H., Dixon, D.J., Luscombe, C.K., Hettstedt, S. and Ley, S.V., Synthesis, structure revision, and absolute configuration of (+)-didemniserinolipid B, a serinol marine natural product from a Tunicate Didemnum sp., Org. Lett., 2002, 4, 3223. 

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