Halichondria okadai

Halichlorine 11 is a structurally unique alkaloid that was isolated from the sponge Halichondria okadai and found to act as an inhibitor of the induction of vascular cell adhesion molecule (VCAM-1), a potential target in the development of drugs for the treatment of several vascular diseases. The strategies employed for the construction of its spiroquinolizidine unit are summarized in Scheme 106. 

II. HALICHONDRINS, ANTITUMOR COMPOUNDS FROM HALICHONDRIA OKADAI... 

We have focused on the identification of natural key compounds that possess biologically and medicinally intriguing functions. Some of bioactive naturally occurring compounds isolated from marine organisms were found to possess unique biological activities. Halichlorine from the marine sponge Halichondria okadai was shown to inhibit the activity of nuclear factor- in endothelial cells and block L-type Ca2+ channels. Thus, it may have therapeutic potentials for diseases such as atherosclerosis and hypertension. 

Kuramoto, M., Chou, T., Yamada, K., Chiba, T., Hayashi, Y., and Uemura, D. (1996). Flalichlorine, an inhibitor of VCAM-1 induction from the marine sponge Halichondria okadai Kadota. Tetrahedron Lett. 37, 3867-3870. 

The quinolizidine alkaloid halichlorine (203), isolated from the marine sponge Halichondria okadai, inhibits the induction of vascular cell adhesion molecule-1 (VCAM-1) at IC50 7 pg/ml, which may be useful for treating atherosclerosis, coronary artery diseases, angina and noncardiovascular inflammatory diseases [161]. 

Three novel related marine alkaloids, halichlorine (1148) from the sponge Halichondria okadai (1177, 1178) and pinnaic acid (1149) and tauropinnaic acid (1150) from the bivalve Pinna muricata (1179), have been the objects of much synthetic interest in view of their pronounced biological activity (inhibition of the vascular cell adhesion molecule-1) (1180). Synthesis of these alkaloids led to both revision and confirmation of the original structures (1181,1182). The syntheses of the previously known chlorine-containing cylindricines have been reviewed (1183). 

Kuramoto M, Tong C, Yamada K, Chiba T, Hayashi Y, Uemura D (1996) Halichlorine, an Inhibitor of VCAM-1 Induction from the Marine Sponge Halichondria okadai Kadota. Tetrahedron Lett 37 3867... 

As with inhibitors produced by eukaryotes, few studies have characterized and quantified inhibitors produced by natural biofilms. Rather, most studies have focused on isolated bacterial strains, or biofilms, cultured in laboratories.98,100-103 Only one inhibitory metabolite from biofilms has been fully characterized, the natural product ubiquinone-8 from the culture supernatant of the bacteria Alteromonas sp.,103 a bacterium isolated from the sponge Halichondria okadai. 

Shigemori, H., Bae, M. A., Yazawa, K, Sasaki, T., and Kobayashi, J., Alteramide A, a new tetracyclic alkaloid from a bacterium Alteromonas sp. associated with the marine sponge Halichondria okadai, J. Org. Chem., 57, 4317, 1992. 

The sponge Halichondria okadai contains a polyether metabohte named okadaic acid (16) that was also isolated as a causative agent of diarrhetic shellfish poisoning (DSP) from mussels and other bivalves (14). However, the real producers are dinoflagellates of the genus Dinophysis. It is a potent cancer promoter that was found to be caused by inhibition of protein phosphatases 1 and 2A at nanomolar levels. Pectenotoxins are also involved in DSP and are produced by Dinophysis spp. pectenotoxin 2 (17) inhibits actin polymerization (14). 

Okadaic acid was first isolated Irom the sponges Halichondria okadai and Halichondria melanodocia and was shown to be ultimately produced by dinoflagellates such as Prow-centrum lima. Okadaic acid contributes substantially to the analysis of phosphorylation and... 

Another unique example was observed for the recently isolated marine natural product, alter amide A (209), isolated from a symbiotic bacteria (Alteromonas sp.) found on the sponge Halichondria okadai. It was found that the tetraene core of this compound underwent intramolecular [4 - - 4]-photocycloaddition upon exposure to sunlight (equation 9). Deliberate irradiation led to a quantitative conversion to cyclooctadiene 210. 

Halichlorine (789) ([a]o +240.7°, c 0.54, MeOH), isolated from the Japanese sponge Halichondria okadai, is a complex alkaloid possessing a novel spiro-quinolizidine macrolide structure (537). Elucidation of the structure was based on detailed analysis of coupling constants and NOE effects in the NMR spectrum The absolute configuration of the ansa chain was inferred by degradation to the... 

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