Halichondria

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. 

The first marine isocyano metabolite was appropriately named axisonitrile-1 (1) based on the trivial name isonitrile and the genus of the sponge, Axinella cannabina, which also furnished axisothiocyanate-1 (2) [1] and, subsequently, a minor constituent, axamide-1 (3) [5]. This observation that isonitriles are often accompanied by isothiocyanates (-N=C=S) and formamides (-NHCHO) was later duplicated by the Hawaiian researchers working with a Halichondria sp. In... 

Amorphanes 38-40 were also isolated from Acanthella cannabina. These are trans-fused and functionalized at C-l rather than C-10 which was the case with the Halichondria metabolites. The carbocyclic skeleton was demonstrated when 39 was dehydrogenated to yield cadalene (37). Relative stereochemistry assignments were secured by extensive 13C- and XH NMR experiments [39], in which 13C data were particularly useful, as illustrated in the case of isothiocyanate 41, one of several isothiocyanates obtained from Acanthella pulcherrima [20]. The ds-fused ring was corroborated by comparing the corresponding chemical shifts with those of enf-epicubenol (42) [20], which has the same relative stereochemistry. 

In a recent study, a Fijian sponge, Axinyssa fenestratus, was found to elaborate four isothiocyanatoamorphanes (43-46) [45]. That this series of compounds may be antipodal to 32 from the Hawaiian Halichondria sp. was indicated by the spectral and optical data of 43 [(1 R,6S,1S, 1 OS)- 10-isocyanato-4-amorphene]. 

From the mixture, a minor component whose double bond was at first assigned incorrectly [61], was isolated as the major metabolite from a Halichondria sp. and identified as 8-isocyano-15,20-cycloamphilect-l(12)-ene (103) [22], X-ray crystallography of 103 and its minor co-metabolites, 104-106, provided relative stereostructures. 

The epimeric compounds, e.g., 88 and 89 from a Hawaiian Ciocalypta sponge [55] and 90 from a Pohnpei Halichondria sp., may share a common sp2-carbon center in the biosynthesis of the bisabolane skeleton of these compounds. 

Another unique example was observed for the recently isolated marine natural product, alteramide A (209), isolated from a symbiotic bacteria (Alteromonas sp.) found on the sponge Halichondria okaclai96. 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. 

Tachibana, K., et al., Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria, JACS, 103, 2469, 1981. 

Marine organisms represent a largely unexplored source of unique toxic chemicals. These toxins are produced by the organisms as defense weapons against their predators. Several potent compounds demonstrating antitumor activity in vitro and in vivo have been isolated from marine organisms, e. g., the bryostatins (from Bugula neritina), dolastin 10 (from Dolabella auricularia) and halichondrine B (from Halichondria okadat) [61]. 

Microbacterium sp. (from Halichondria panicea) Glucosylmannosyl glycerolipid 200 [84]... 

Schneemann, I., Nagel, K., Kajahn, I., Labes, A., Wiese, J., and Imhof, J. F. (2010). Comprehensive investigation of marine actinobacteria associated with the sponge Halichondria panacea. Appl. Environ. Microbiol. 76, 3702-3714. 

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