Dendrodoine

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>. 

The structure of the cytotoxic metabolite dendrodoine (81) from the tunicate Dendrodoa grossularia was determined by X-ray analysis [103] and it was later synthesised by a convergent route [104],... 

Novel indole derivatives continue to be found in marine organisms those reported recently include dendrodoine (3), a cytotoxic thiadiazole derivative, which occurs in the tunicate Dendrodoa grossularia, from Brittany,4 and the keto-lactam (4), one of two lactams isolated from the Caribbean sponge Hali-chondria melanodocia.5... 

Investigation of animals from the marine enviroiunent has thrown up an intriguing variety of poly-heterocyclic products (sometimes called sea alkaloids) five representatives are variolin B (sponge, Kirkpatrickia varialosa), lamellarin B (mollusc, Lamellaria sp.), ascididemine (mnicate, Didemnum sp.), wakayin ° (ascidian, Clavelina sp.) and dendrodoine" (tunicate, Dendroda grossular), a rare natural example of a multi-heteroatom compound. 

Multihetero atom heterocycles are comparatively rare in nature, dendrodoine, a cytotoxic substance from a marine tunicate, is an example, however in medicinal chemistry they are of considerable significance Alprazolam is a major drug for the treatment of anxiety, Acetazolamide is an inhibitor of the enzyme carbonic anhydrase and is used principally for the treatment of glaucoma, and Fluconazole, is an antifungal agent. 

Dendrodoine (109) [80,81], the related aminoimidazole (110) analogue [82] and the recently reported oxadiazinone, alboinon (111) [83] were reported from Dendrodoa grossularia. There are structural similarities between these tryptophane-derived metabolites, the phenylalanine-derived metabolites (5), (6) and (7), and the tyrosine-derived metabolite... 

The First S -N Bond in a Natural Product —Dendrodoine, of which 98 mg was isolated from 2.2 tonnes of a marine tunicate, Dendrodoa grossularia (Styelidae), has been shown by JT-ray and spectral data to be an indole derivative of 1,2,4-thiadiazole (139). A noteworthy feature is that, as far as this Reporter is aware, this is the first natural product with a sulphur(ii)-nitrogen bond. All the other fourteen possible combinations of the five common biological elements (C, H, N, O, and bivalent S) are elaborated by living cells only S—N has, so far, been missing. 

Polycarpathiamines A and B were isolated from the ascidian P. aurata [48]. In general, marine invertebrates such as ascidians are prominent sources of a wide variety of nitrogenous compounds, many with novel stmctures. The authors were led to the 1,2,4-thiadiazole family based on the shift of one of the quaternary carbons at 170 ppm and the second in the 180-190 ppm range. The C NMR data for the previously reported indole alkaloid dendrodoine [49], which also contains an N,Af-dimethyl-l, 2,4-thiazole moiety provided further support for the incorporation of a 1,2,4-thiadiazole moiety in the structures of the polycarpathiamines. The constitution of the thiadiazole was based on H—HMBC data. As shown in Scheme 3, the authors assigned the substitution based on the observation of correlations from the amino protons to both nitrogens of the... 

Hogan, I.T., and M. Sainsbury The Synthesis of Dendrodoine, 5-[3-(N,N-Dimeth-ylamino)-l,2,4-thiadiazolyl]-3-indolylmethanone, a Metabolite of the Marine Tunicate Dendroda grossular. Tetrahedron 40, 681 (1984). 

Hogan, I.T. and Sainsbury, M. (1984) The synthesis of dendrodoine a metabolite of the tunicate Dendrodoa grossularia (S-3-(N,N-dimethylamino-l,2,4-thiadiaxolyl)-3-indolylmethanone. Tetrahedron, 40, 681-682. 

---