Dysidenin

Dysidea herbacea contains linear polychlorinated peptides with a thiazole residue. The metabolites can be divided into the dysidenin, the isodysidenin and the dysideathiazole series of compounds [22]. 

Dysidenin (318) was isolated from D. herbacea from Cooktown, Australia without stereochemical assignments [288]. The structure of isodysidenin (319), isolated from a sample of D. herbacea from Papua New Guinea, was determined by X-ray diffraction analysis [289]. It was proposed that the two compounds differ in stereochemistry at C5 [290]. The absolute configurations were later revised [291]. 

Dysidea sp. from Bararin Island in the Philippines, has yielded the dysideaprolines A-F (341-346), proline-derived analogues of dysidenin (318). The barbaleucamides A (347) and B (348), which are structural analogues of the cyanobacterial metabolite barbamide, were also isolated. The structures were elucidated by NMR spectroscopic analysis. It is most probable that all of these compounds are derived from a symbiotic cyanobacterium found in close association with the Dysidea sp. [306]. 

Dysidenin (419) has been shown to have inhibition activity of the iodide transfer in thyroid cells through a different mechanism than ouabain [332]. Dysideathiazoles (420-424) were strongly deterrent in fish-feeding experiments [326] and barbamide (426) has shown molluscicidal activity [328]. 

The simple herbacic acid (938) was isolated from Dysidea herbacea from the Great Barrier Reef, and may be a precursor to more complex trichloromethyl metabolites (990). Another collection of Dysidea sp. from Australia s Great Barrier Reef yielded five new metabolites (939-943) for which the absolute stereochemistry was determined by correlation with (-)-(.S )-4,4,4-trich loro-3-methyl butanoic acid (991). Dysidea herbacea from the Great Barrier Reef contains (-)-neodyside-nin (944), which is an isomer of the well-known and often isolated dysidenin. 

This new metabolite belongs to the L-series of trichloroleucine peptides and is a rare example of a non-/V-methylated trichloroleucine amino acid (992). Another sample of this sponge from the same locale has yielded the new thiazoles 945 and 946, which are also related to dysidenin (993). The Panamanian Lyngbya majuscula has afforded the new dysidenamide (947), pseudodysidenin (948), and nordysidenin (949), which is the first report of dysidenin-like compounds from a free-living cyanobacterium (994). 

A study of a Philippines Dysidea sp. has yielded the novel proline analogs of dysidenin, dysideaprolines A-F (950-955) and barbaleucamides A (956) and B (957), which are reminiscent of barbamide (995). Also from the Philippines was isolated the novel pyrrolidone 958 from the nudibranch Asteronotus cespitosus (996), which is the first example of a Dysidea-type polychlorinated metabolite found in a carnivorous mollusc. An Indonesian collection of Dysidea sp. has furnished dysithiazolamide (959), having the suggested absolute configuration shown (997). 

The Red Sea sponge Lamellodysidea herbacea contains the new dysidamides D-H (960-965) and ring-opened analogs 966 and 967 998). As has been pointed out several times 999), the determination of absolute stereochemistry of the Dysidea polychlorinated peptides has been difficult and revisions are not uncommon. The X-ray crystal structure of a zinc chelate of dechlorinated dysidenin has confirmed its absolute configuration as (55,135) as shown in UU 999). 

Trousdale EK, Taylor SW, Parkin S, Hope H, Mokinski TF (1998) Reductive Dechlorination of Dysidenin from Dysidea herbacea. Structure of a Novel Binuclear Zinc Metallo-cycle. Nat Prod Lett 12 61... 

Van Sande J, Deneubourg F, Beauwens R, Braekman JC, Daloze D, Dumont JE (1990) Inhibition of Iodide Transport in Thyroid Cells by Dysidenin, a Marine Toxin, and Some of Its Analogs. Mol Pharmacol 37 583... 

Several thiazole-containing linear peptides such as dysidenin, isodysidenin, and dysidin have been isolated from marine invertebrates and their absolute configurations have been established (80T2133, 93JOC6336,95TLii85>. However, the total synthesis of any of these compounds has not been reported. 

Biskupiak, J.E., and C.M. Ireland Revised Absolute Configuration of Dysidenin and Isodysidenin. Tetrahedron Lett. 25, 2935 (1984). 

De Laszlo SE, Williard PG. Total synthesis of (+)-demethyl-dysidenin and (—)-demethylisodysidenin, hexachlorinated amino acids from the marine sponge Dysidea Herbacea. Assignment of absolute stereochemistry. J. Am. Chem. Soc. 1985 107(1) 199-203. 

Ilardi EA, Zakarian A. Efficient total synthesis of dysidenin, dysidin, and barbamide. Chem. Asian J. 2011 6(9) 2260-2263. 

Biskupiak, J.E. and Ireland, C.M. (1984) Revised absolute configuration of dysidenin and isodysidenin. Tetrahedron Lett., 25, 2935-2936. 

Charles, C., Braekman, J.C., Daloze, D., and Tursch, B. (1980) Chemical studies of marine invertebrates XLll. The relative and absolute configuration of dysidenin. Tetrahedron, 36, 2133-2135. 

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