Aerothionin

Naturally occurring dimeric spiroisoxazolines (+)-aerothionin (52) and (+)-calafianin (53) have been synthesized in enantiopure form and their configuration unambiguously assigned <06TL727 06OL927>. 

A dibromotyrosin-derived metabolite present at 1.0% sponge dry weight, aerothionin (148), from Aplysina fistularis completely inhibits fish feeding when assayed in a 1.0% food pellet [115]. 

The Mexican sponge Aplysina gerardogreeni contains calafianin (2106) (1880) (structure revised and confirmed by total synthesis, (1881-1883)), the known aerothionin, and the new phenylacetic acid 2107 (1880). These studies confirm that calafianin (2106) and aerothionin have the same absolute configuration (1883). Whereas aerothionin displays antibacterial activity against Mycobacterium tuberculosis, calafianin does not (1884). The Brazilian sponge Aplysina caissara contains the new caissarines A (2108) and B (2109) (1885). 

Thompson JE, Barrow KD, Faulkner DJ (1983) Localization of Two Brominated Metabolites, Aerothionin and Homoaerothionin, in Spherulous Cells of the Marine Sponge Aply-sina fistularis (=Verongia thiona). Acta Zoologica 64 199... 

Encamacion-DimayugaR, Ramirez MR, Luna-Herrera J (2003) Aerothionin, aBromotyro-sine Derivative with Antimycobacterial Activity from the Marine Sponge Aplysina gerardogreeni (Demospongia). Pharm Biol 41 384... 

Thompson, J. E., Barrows, K. D., and Faulkner, D. J., Localization of two brominated metabolites, aerothionin and homoaerothionin, in spherulous cells of the marine sponge Aplysina fistularis (= Verongia thiona), Acta Zool., 64, 199, 1983. 

Thompson et al. have investigated the ecological role of the brominated isoxazoline alkaloids, aerothionin (Structure 2.84) and homoaerothionin (Structure 2.89), in Californian specimens of A. fistularis.134 139 The alkaloids caused behavioral modification in marine invertebrates, were toxic to dorid nudibranchs other than one specialized feeder, inhibited the settlement and/or metamorphosis of invertebrate larvae, and were strongly antimicrobial and cytotoxic. Sponges exuded significantly more of these two alkaloids when wounded,155 and, consistent with their defensive role, the metabolites were found to be localized in spherulous cells close to the aquiferous exhalant canals.156... 

Aerothionin, a tetrabromo derivative, has been isolated from sponges Aplysina aerophoba and Verongia thiona the proposed structure is 24 (46). The oxime 25 was formed by treatment of aerothionin with dilute alkali. The relative positions of the aromatic substituents in 25 were established by cleavage in hot 6 N HC1 to give 26 and a lactone subsequently converted by methylation to 27. The tetramethyl derivative of 25 was hydrolyzed to form... 

Ten years later the same aerothionin was isolated from a different sponge. X-Ray structure determination in addition to CD data were employed to assign its absolute configuration (47). 

Yamamura and coworkers have used a thallium trifluoroacetate mediated oxidative cyclization in their synthesis of aerothionin and related products and also in the synthesis of bastadin-6, a 28-membered ring lactone. 

The planar structure, except the geometry of a C8 double bond, was initially proposed shown in Fig. (9) by the detailed analysis of ID and 2D NMR (COSY, HMQC and HNBC) data and by comparison of its and NMR spectra with those of structurally related compounds such as aerothionin (18), purealin (19) and others [30-41]. Although the DQF-COSY spectrum of 17 showed few H- H correlations, the HMBC spectrum was very useful for elucidating the planar structure of 17. The geometiy of C8 double bond was elucidated by a NOESY H7 /NH correlation to be trnas. The relative stereochemistry of 17 was clarified by... 

Kigoshi and co-workers recently isolated zamamistatin (17) from a sponge Pseudoceratina sp. [42]. In the spectral analysis of 17, they found tW the chemical shift of C6 (5ce 74.3) and C7 (8c 26.7) in 17 were different from those (See 91.5 and 8cy 40.2) of aerothionin (18), which let them reconsider its structure, Fig. (12). Considering the molecular formula of 17, they proposed a structure possessing a dihydro-1,2-oxazine ring for 17. To confirm this, they prepared dihydro-1,2-oxazine derivatives, 17a and 17b, Scheme (6) [42-45] and compared the CNMR data for 17 with those of 17a, 17b and the known 17c [45]. The CNMR data of synthetic 17a and 17b were similar to those of zamamistatin (17) rather than aerothionin-related compounds, Fig (12). Base on these observations it was concluded that the structure of zamamistatin should be revised to an endo-type dimmer. 

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