Biosynthesis brominated tyrosines

Carney JR, Rinehart KL (1995) Biosynthesis of Brominated Tyrosine Metabolites by Aplysina fistularis. J Nat Prod 58 971... 

The fantastic stmctural diversity of the natural brominated tyrosines has led to equally ingenious biosynthesis proposals, but only a few definitive labeling studies have been described. The early study by Tymiak and Rinehart on the biosynthesis of dibromotyrosine metabolites by the sponge Aplysina fistularis supports the incorporation of both phenylalanine (127) and tyrosine (128) into dienone 133 and dibromohomogentisamide (134) (Scheme 19.6) [120]. Metabolites 131,132, 135, and 136 were also identified along with 133 and 134 in this study, which utilized... 

Crews has formulated a collective scheme for the biosynthesis of the sponge metabolite bastadins based on the knovm structures (Scheme 19.8) [123]. Thus, dimerization of two brominated tyrosines can lead to hemibastadins 14S, which in turn can couple to form prebastadins 146. Final ring closure can afford bastadins 147 or isobastadins 148. The final cyclization is similar to the formation of polybromi-nated dibenzo-p-dioxins from polybrominated diphenyl ethers, which are ubiquitous in sponges [124,125]. 

The biosynthesis of synoxazolidinones A (1) and B (2) was postulated by Tadesse and coworkers and it is depicted in Scheme 1. It was assumed that brominated tyrosine derived metabolite 4 [11, 12] and an arginine /agmatine derivative 5 [13] react with each other and form a dipeptide 6, which further cyclize to form oxazolidinone ring. The biosynthesis of synoxazolidinone C (3) has not been studied and it was assumed that synoxazolidinone C (3) might be derived Irom synoxazolidinone A (1) [9]. 

Quite surprisingly V. aerophoba failed to incorporate radioactivity from [U- " C]-L-tyrosine into aerothionin (7), aeroplysinin-1 (4) and the dienone (1) inactive aerothionin was also isolated when the animals were fed with [U- " C]-L-ornithine (71). However the sponges utilized these aminoacids for the synthesis of fatty acids. A very slow rate of biosynthesis might account for these results. A dietary origin for these compounds can be also suspected in this connection the recent report of the isolation of the brominated esters (19) and (20) (after methylation) from hydrolyzed extracts of the red alga Halopytis incurvus (41) seems relevant. 

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