Tyrosine halogenated

Anodic oxidation of halogenated tyrosines was studied in connection with some sponge metabolites (cavemicolin model compounds). The methyl exter of 3,5-dibromotyrosine afforded four different products in a 41 10 26 23 ratio with 23% overall yield as a result of equilibration. (Scheme 44) [93JCS(P2)3117], A related compound was obtained as a mixture of stereoisomers 56 from a Diels-Alder reaction between N-acetyldehydroalanine methyl ester and l-methoxy-l,3-cyclohexadiene (87TL2371). 

Although relatively few simple halogenated tyrosines are found naturally, many transformed tyrosines are produced by marine organisms and these are covered in Sects. 3.22.3.2-3.22.3.4. 

The thyroid protein, thyroglobulin, contains 3-monoiodotyrosine, 3,5-diiodotyrosine and several iodinated thyronine derivatives (Salvatore and Edelhoch 1973). lodohistidines may also be present in this protein. 3-Bromotyrosine has been reported in serum proteins (Firnau and Fritze 1972). Methods for separating and analyzing these and other halogenated tyrosines are presented in 2.2.3. 

TPO is highly efficient in the two-electron oxidation of iodide to iodonium, which quickly reacts with the tyrosine residues of the Tg protein. The presence of iodo substituents on halogenated tyrosines favors the C—O coupling reaction when oxidized by Cpd I of TPO. 

In an effort to compare the halogenated tyrosine derivatives from Desmospongiae Makarieva et al. (149) investigated 22 species of eleven Demospongiae families and identified 10 substances of this type in Aplysina (Verongia), Verongula, and Aiolochroia species. It has been shown that animals of the Aplysinidae family biosynthesize all three forms [(-I-), (—), (+) = racemate] of aeroplysinin-1 (233) and of an... 

Dellar, G., P. Djura, and M.V. Sargent Structure and Synthesis of a New Bro-moindole from a Marine Sponge. J. Chem. Soc., Perkin Trans. 1 1981, 1679. Makarieva, T.N., V.A. Stonik, P. Alcolado, and Y.B. Elyakov Comparative Study of the Halogenated Tyrosine Derivatives from Demospongiae (Porifera). Comp. Biochem. Physiol. 68B, 481 (1981). 

In this review, we discuss the isolation, structure, physicochemical and spectral data of all bromotyrosine derivatives isolated from marine organisms. The biosynthesis, total synthesis, and bioactivity of the bromotyrosine derivatives are also reviewed. Neither tyrosine derivatives without halogenation, nor indole alkaloids (with or without halogenation), are included in this review. Proteins or peptides containing bromotyrosine units are not included in this review since they are considered as primary metabolites. Cyclopeptides containing halogenated tyrosine units are, however, discussed in this review. 

There are a number bromotyrosine derived compounds not belonging to any of the above structure classes. Geodiamolides, a series of cyclic depsipeptides, are included in this review since they contain halogenated tyrosine. Polycitones and polydtrins are condensation products of substituted bromotyrosine molecules, isolated from ascidians, and are also included in this review. Similar structures including lamellarins are not included due to the absence of halogenation. For the same reason, polyandrocarpamides A-C (253-255), chelonin B (256), and 5-bromochelonin B (257) are included. 

Chloro-5 -bromotyrosine (42) was identified from hydrolysates of a sclero-protein constituting the operculum of the gastropod mollusk Baccinum undatum in 1971 34). A,A,iV-Trimethyl halogenated tyrosines, 43, 44, 45, and 46 were isolated from the Caribbean sponge Pseudoceratina crassa by Fattorusso s group 35). The absolute stereochemistries of 43 and 44 were determined to be L by Gao and Hamann 36). 

Figure 1.11 Tyrosine residues are subject to nucleophilic and electrophilic reactions. The unprotonated phe-nolate ion may be alkylated or acylated using a variety of bioconjugate reagents. Its aromatic ring also may undergo electrophilic addition using diazonium chemistry or Mannich condensation, or be halogenated with radioactive isotopes such as 12iI.

Figure 12.3 The strong oxidant chloramine-T can react with iodide anion in aqueous solution to form a highly reactive mixed halogen species. 125IC1 then can modify tyrosine and histidine groups in proteins to form radiolabeled products.

Figure 12.5 IODO-GEN is a water-insoluble oxidizing agent that can react with 1251 - to form a highly reactive mixed halogen species, 125IC1. This intermediate can add radioactive iodine atoms to tyrosine or histidine side chain rings.

A number of the reactions in which HOCl and O2 might participate to kill bacteria and to attack biological molecules have been documented. These include the halogenation of tyrosines, the formation of aldehydes and chloramines, the attack of Oj on unsaturated bonds in fatty acids, and decarboxylation of amino acids. The experimental basis for these reactions has been reviewed by Klebanoff and Clark... 

Organic Acids. Hydrochloric acid will show a propensity to cause degradation of amino acids by halogenation (especially in procedures that employ peroxide treatment). This can be especially troublesome for tyrosine and phenylalanine. Thus, alternative acids that do not pose a risk for halogenation have been investigated. 

The reaction of IODO-GEN with iodide ion in solution results in oxidation with subsequent formation of a reactive, mixed halogen species, IC1 (Fig. 266). Either 125I or 13 1 can be used in this reaction. The IC1 then rapidly reacts with any sites within target molecules that can undergo electrophilic substitution reactions. Within proteins, any tyrosine and histidine side-chain groups can be modified with iodine within... 

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). 

Jonsson M, Lind J, Reitberger T, Eriksen TE, Merenyi G (1993) Free radical combination reactions involving phenoxyl radicals. J Phys Chem 97 8229-8233 Kapoor SK, Gopinathan C (1992) Reactions of halogenated organic peroxyl radicals with various purine derivatives, tyrosine, and thymine a pulse radiolysis study. Int J Chem Kinet 24 1035-1042 Khaikin Gl, Neta P (1995) Formation and reactivity of vinylperoxyl radicals in aqueous solutions. J Phys Chem 99 4549-4553... 

---