Aeroplysinin

Aeroplysinin-1 (84) has been obtained from marine sponges belonging to the order Verongida. The first isolation of (+)-aeroplysinin-1 from Verongia aerophoha collected in the Bay of Naples (Italy) was reported by Fattorusso et al. in 1970 [77]. Since then, (-r)-aeroplysinin-l has been reported from a number of marine sponges from various geographic locations (see Table 9.2) and the (—)-isomer has been isolated from lanthella ardis ]78]. 

Taxonomic identification Collection sites Enantiomer References 

The structure of (+)-aeroplysinin-l was deduced from analysis of its ultraviolet (UV), infrared (IR), and NMR, and MS data [77]. The proposed structure was confirmed by chemical degradation experiments in which the degraded material was found to be identical with methyl 3,5-dibromo-2-hydroxy-4-methoxyphenylacetate (8S). Cosulich et al. confirmed the structure and relative configuration of the (—)-isomer by X-ray crystallographic analysis [85] while Fulmor et al. determined the absolute configuration of (—)-84 on the basis of circular dichroism [78]. 

Reagents and Conditions a) Constant potential electrolysis, nBu4NCI04, CH3CN, Pt wire (cathode)-glassy carbon beaker (anode) b) Zn(BH) 4, CH2CI2, RT, 10 min c) TBSOTf, 2,6-lutidine, CH2CI2, 0° C, overnight d) NaOH, aq MeOH, RT, 30 min e) DMF, 60 °C, 2h f) TBAF, THF, 0°C, 1h. 

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Upon tissue disruption, the isoxazoline alkaloids 76 and 78 are converted to aeroplysinin-1 (79), which subsequently provides the dienone (80) (Scheme 21). 

Fattorusso, E., Minale, L., Sodano, G., Moody, K., and Thomson, R. H. (1970). Aeroplysinin-I, a new bromo-compound from Aplysina aerophoba.. Chem. Soc. Chem. Commun. 751-752. 

Other biologically active bromotyrosine-derived metabolites of marine origin include aeroplysinin, Fig. (48) as cytotoxic and tyrosine kinase inhibitor [382,383], fistularin isolated from Aplysina circheri which exhibited antiviral activity [384], and ceratinamides A and B, antifouling metabolites from Pseudoceratina purpurea [385],... 

Ogamino T, Nishiyama S (2003) A New Ring-Opening Access to Aeroplysinin-1, a Secondary Metabolite of Verongia aerophoba. Tetrahedron 59 9419... 

Scheme 9.9 Enzymatic transformation of isoxazoline alkaloids in Aplysina sponges into aeroplysinin-1 (84) and a dienone analog (86).

Scheme 9.10 Andersen and Faulkner s racemic synthesis of aeroplysinin-1 (84) [96],...

A subsequent study by Carney and Rinehart provided additional evidence for the biosynthesis ofbrominated tyrosine metabolites [121]. Thus, [U- " C]-L-tyrosine (128), [U- " C]-L-3-bromotyrosine (137), and [U- " C]-L-3,5-dibromotyrosine (129) are incorporated into both dibromoverongiaquinol (133) and aeroplysinin-1 (142). Moreover, [methyl- Cjmethionine is specifically incorporated into the O-methyl group of aeroplysinin-1 (142). These experiments led to the proposed biogenetic path vay sho vn in Scheme 19.7 [121]. 

Aeroplysinin-1 (852), a metabolite of marine organisms, shows antibiotic activity against Staphylococcus aureus and antileukemia activity against L-1210. This metabolite was synthesized by Pb(OAc)4-mediated phenolic oxidation as a key step. Here, 3,5-dibromo-2-hydroxy-4-methoxyphenylacetonitrile (853) was oxidized with excess of Pb(OAc)4 in AcOH to give in 35% yield the desired cyclohexa-2,4-dienone 854, which was converted to the target molecule in 2 steps. 

Adamantyl haUdes, reactions of 677 p-(l-Adamantyl)phenols, synthesis of 606, 607 Aerophobin-1, biosynthesis of 1315, 1316 Aeroplysinin-1, synthesis of 1327, 1328 Aerothionin, biosynthesis of 1315, 1316 Ageing, free-radical theory of 140, 141 Agent Orange 12... 

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