Aplysinopsin

The relationship between anemone fish, Amphiprion sp., and their sea anemone partners are regulated by alkaloids from the sea anemone. Amphiprion perideraion is attracted to the sea anemone Radianthus kuekenthali by the simple lysine-derived alkaloid amphikuemin (Fig. 12.6 Murata etal, 1986). Other simple alkaloids, aplysinopsin and dihydroaplysinopsin, also attract A. perideraion, regulate its swimming rate and induce their species-specific partnership. A related anemone fish, Amphiprion ocellaris, is attracted to the sea anemone Stoichactis kenti by tyramine (Fig. 12.6) and tryptamine induces searching by the fish (Murata etal, 1986). 

Chemical bias toward certain molecular arrangements may also determine the commonness of certain metabolites (Pietra 1995), such as the aplysinopsins (indole alkaloids of many sponges, cnidarians, and mollusks. Chart 8.2. A), bis-indole and guanidine alkaloids (Chart 8.2.A), isoprenoids (Pietra 1995, Chart 8.2.1), and polypropionates of mollusks, sponges, and fungi (Chart 8.2.FA/PO). 

Alkyl 3-dimethyl-2-(177-indol-3-yl)propenoates have found an important role in the synthesis of 3-heteroarylindoles as part of a program aimed at the total synthesis of aplysinopsins and related cytotoxic compounds (Scheme 44)... 

Aoki S, Ye Y, Higuchi K, Takashima A, Tanaka Y, Kitagawa I, Kobayashi M (2001) Novel Neuronal Nitric Oxide Synthase (nNOS) Selective Inhibitor, Aplysinopsin-Type Indole Alkaloid, from Marine Sponge Hyrtios erecta. Chem Pharm Bull 49 1372... 

Another large group of brominated tryptophan-derived marine alkaloids are the aplysinopsins and several new examples have been reported. The sponge Hyrtios erecta has furnished 20 and 21[26], while a New Zealand asddian is the source of kottamides A-E, for example A (22) [27] and E (23) [28], The stony coral Tubastraea sp. contains the structurally complex and unprecedented bisindole tubastrindole A (24) [29]. 

Some new six-membered Aplysinopsin analogues, 5-(17f-indol-3-ylmethylene)-2,4,6(17f,3/7,5//)-pyrimidinetriones 678, were prepared in 11-73% yield from indole derivatives 676 and 5-[(dimethylamino)methylene]-2,4,6(l/7,3/7,5//)-pyrimidinetriones 677 by heating in glacial acetic acid (Equation 162) <2001T3159>. 2-Methylindole reacts with pyrimidinetrione 677b (when R = Me) in a different manner from 677a (when = H). Instead of the expected 3-vinylindole 678, 3-[bis(2-methyl-l//-indol-3-yl)methyl]-2-methyl-l//-indole 679 was isolated in 71% yield (Scheme 135). 

KH Hollenbeak, FJ Schmitz. Aplysinopsin antineoplastic tryptophan derivative from the marine sponge verongia spengelli. Lloydia 40 479-481,1977. 

Examples of five-membered heterocyclic rings prepared by aza-Wittig and related methods include the alkaloid leucettamine B (206) and pyrrolo[2,3-b]pyridines (207) (Scheme20). The aza-Wittig reactions of the iminophosphorane (208) with methyl isocyanate, carbon dioxide, or carbon disulfide give heterocumulenes (209), (210), and (211), respectively, which react with amines or ammonia to provide a route to the framework of aplysinopsin alkaloids (212). ... 

The synthesis of aplysinopsins, meridianines, and related compounds of marine origin 05MRO211. 

Fusetani, N., Asano, Matsunaga, S., Hashimoto, K., (1986). Bioactive marine metabolites. XV. Isolation of aplysinopsin from the scleractinian coral Tubastrea aurea as an inhibitor of development of fertilized sea urchin eggs. Comp. Biochem. Phys. B 85B, 845-846. 

Guella, G., Mancini, 1., Zibrowius, H., Pietra, F., (1989). Aplysinopsin-type alkaloids from Dendrophyllia sp., a scleractinian coral of the family Dendrophylliidae of the Philippines. Facile photochemical (Z/E) photoisomerization and thermal reversal. Helv. Chim. Acta 72,1444-1450. 

Aoki, S., Ye, Y., Higuchi, K., Takashima, A., Tanaka, Y., Kitagawa, 1., Kobayashi, M., (2001). Novel neuronal nitric oxide synthase (nNOS) selective inhibitors, aplysinopsin-type indole alkaloids, fix)m marine sponge Hyrtios erecta. Chem. Pharm. Bull. 49, 1372-1374. 

By aza-Wittig reactions of iminophosphoranes with isocyanates, carbodiimide-mediated syntheses of pyrrole and indole derivatives [1270], pentasubstituted pyridines [1271], pyrimidine derivatives [1272-1274], bis( -ferrocenylvinyl)carbo-diimide [1274], amino-tetrazolyl-deoxythymidines [1275], the marine alkaloid leu-cettamine B [1276], and aza-analogues of aplysinopsins [1277] have also been accomplished. 

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