Tyrosine, bromination

A very old gas-solid bromination of tyrosine (280) [97] has been revisited and it gave a quantitative yield for the reaction of rac-280 [22]. The doubly bromi-nated hydrobromide rac-281 is spectroscopically pure after removal of included gases at 50 °C in a vacuum. Quite spectacular is the specific and quantitative waste-free gas-solid tetrabromination of tetraphenylethylene (282), which shows some signs of autocatalysis and requires rotation of the flask around a horizontal axis at room temperature for 12 h as the reactant and product gases require mixing [60]. The isomer-free tetrabromide 283 is an attractive starting point for dendrimer syntheses and inclusion studies (Scheme 40). Also 4-bro-mo antipyrin hydrobromide is quantitatively obtained from antipyrin(hydro-bromide) and bromine vapor [22]. 

A new method of determining the presence of tyrosine by bromina-tion was introduced by Horace Brown and employed by Adrian Brown and Millar in 1906 for estimating the rate at which tyrosine is split off from proteins by the action of trypsin. This method might be used for the estimation of tyrosine in proteins its non-employment may be due to the fact that tryptophane and also histidine react with bromine and might thus vitiate the result for tyrosine. 

Neuberg and Popowsky, as also Abderhalden and Kempe, have introduced a few alterations in the procedure, such as evaporation in vacuo, and Levene and Rouiller suggested in 1906 that the tryptophane, on account of its proneness to decompose on evaporation of its solution with consequent loss, be estimated colorimetrically the mercury sulphate precipitate is decomposed, and the solution, freed from hydrogen sulphide, is titrated with bromine water in presence of amyl alcohol. Both cystine and tyrosine react with bromine water the latter can, however, be removed, but for the former a correction has to be made. Up to the present no values concerning the amount of tryptophane in various proteins have appeared, and it will be of interest to see if the values so obtained are very much higher than those obtained by crystallisation of the tryptophane. 

Bisebromoamide is cytotoxic linear peptide isolated from the marine cyanobacterium Lyngbya sp. (Teruya et al., 2009). Structure of bisebromoamide contains rich unusual amino acid derivatives with D-amino acids, N-methylated amino acids, a brominated tyrosine, a modified 4-methylpro-line, a 2-substituted thiazoline-4-methyl-4-carboxylic acid unit, and a rare... 

Hunt, S. I., Breuer, S. W. Chlorinated and brominated tyrosine residues in molluscan sclero-proteins. Biochem. Soc. Trans. 1, 215 (1973)... 

NADH-dependent reductase, thus allowing the biopterin cofactor to function catalytically (72JBC(247)6082). That the conversion of phenylalanine to tyrosine involves an arene oxide intermediate is suggested by the observation of the so-called NIH shift phenomenon (i.e. migration and retention of the para substituents such as deuterium, tritium, methyl and bromine when these para-substituted phenylalanines are enzymatically hydroxylated) <66BBR(24)720, 67MI11000). 

This section and the section on alkaloids in the first survey (7) are artificially small since many halogenated alkaloids are presented in the sections on pyrroles, indoles, carbolines, tyrosines, and other nitrogen heterocycles. It might be noted that the very large number of brominated alkaloids that are obviously tyrosine-derived are now included in Sect. 3.22.3 (Tyrosines). 

Marine tunicates are also a source of brominated tyrosine derivatives. The colonial ascidian Aplidium sp., which was collected in Australia, yielded the novel iodinated tyrosine alkaloids 1973-1975 (1819). Collections of Botryllus sp. and Botryllus schlosseri from the Philippines and the Great Barrier Reef, respectively, have afforded botryllamides A-D (1976-1979) (1820). A Palauan ascidian Botrylloides tyreum produces several new botryllamides, including the brominated botryllamide G (1980) (1821). The simple brominated tyramines 1981 and 1982 were isolated from the New Zealand ascidian Cnemidocarpa bicornuta (1822) and an Indonesian Eudistoma sp. ascidian (1823). 

The toxic Japanese gastropod Turbo marmorata contains the two toxins, turbotoxins A (1983) and B (1984), isolated as bis-trifluoroacetates (1824, 1825). The turbotoxins A and B show LD99 = 1.0 and 4.0 mg kg 1 in mice. The simple iodinated ammonium salt 1985 is also found in this animal (1826). The red alga Halopytis incurvus contains the simple brominated phenols 1986 and 1987, which were isolated as the methyl esters and methyl ethers (1827). These presumed degradation products of tyrosine are related to earlier reported brominated metabolites (1). 

In contrast to MPO, eosinophil peroxidase (EPO) prefers to oxidize plasma level bromide (20-100 pM) to hypobromous acid (HOBr) and several biological targets are implicated, including nucleic acids and nucleosides (1480, 1482, 2376), proteins (1812, 1813, 2377, 2378), unsaturated fatty acids (2379), and low-density lipoprotein (2380, 2381). This EPO-dependent bromination is suggested to be involved in the pathogenesis of asthma (2382). Accordingly, both 3-bromotyrosine and 3,5-dibromotyrosine (1812,1813) are produced by EPO-induced bromination of tyrosine residues in lung tissue (1813, 2382). 

Purealin, another brominated tyrosine metabolite of the sponge Psammaplysilla purea, blocks the sliding movement of sea urchin Anthocidaris crassispina sperm flagella (2537). Numerous sponge metabolites are feeding deterrents to predatory... 

McDonald LA, Swersey JC, Ireland CM, Carroll AR, Coll JC, Bowden BF, Fairchild CR, Cornell L (1995) Botryllamides A-D, Two Brominated Tyrosine Derivatives from Styelid Ascidians of the Genus Botryllus. Tetrahedron 51 5237... 

Sorek H, Rudi A, Aknin M, Gaydou E, Kashman Y (2006) Itampolins A and B, New Brominated Tyrosine Derivatives from the Sponge lotrochota purpurea. Tetrahedron Lett 47 7237... 

Aoki S, Cho S, Ono M, Kuwano T, Nakao S, Kuwano M, Nakagawa S, Gao J-Q, MayumiT, Shibuya M, Kobayashi M (2006) Bastadin 6, a Spongean Brominated Tyrosine Derivative, Inhibits Tumor Angiogenesis by Inducing Selective Apoptosis to Endothelial Cells. Anti-Cancer Drugs 17 269... 

Aoki S, Cho S, Hiramatsu A, Kotoku N, Kobayashi M (2006) Bastadins, Cyclic Tetramers of Brominated-Tyrosine Derivatives, Selectively Inhibit the Proliferation of Endothelial Cells. J Nat Med 60 231... 

Kotoku N, Tsujita H, Hiramatsu A, Mori C, Koizumi N, Kobayashi M (2005) Efficient Total Synthesis of Bastadin 6, an Anti-Angiogenic Brominated Tyrosine-Derived Metabolite from Marine Sponge. Tetrahedron 61 7211... 

Yang ZP, Shelton KD, Howard JC, Woods AE (1995) Mechanism of the Chloroperoxidase-Catalyzed Bromination of Tyrosine. Comp Biochem Physiol 111B 417... 

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

Among these keratose sponges, Aplysina aerophoba (Verongida) is said to be at least capable of biotransformation of the characteristic brominated tyrosine derivatives.46 They are held, evidently... 

Other peroxidase enzymes have been found to halogenate various substrates. Thus lac-toperoxidase catalyzes the bromination of tyrosine, thyroglobulin and bovine serum albumin380, and myeloperoxidase brominates nucleic acids and related compounds381. 

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... 

Interestingly, a study of the bromide-dependent chloroperoxidase bromination of tyrosine reveals that the active brominating agent is free bromine and not a bromine-enzyme complex [122]. The situation is very different for bromoperoxidase- and vanadium peroxidase-catalyzed brominations [106-108]. 

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]. 

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