4-Bromotryptophan

Relatively little is known concerning the substitution reactions of the carbolines. The most studied reaction is that of nitration. Nitration of l-methyl-j8-carboline gave two mononitro derivatives. The highermelting isomer, which was formed predominantly (57% yield), was shown to be 6-nitro-l-methyl-j8-carboline (253 R = CH3) by its conversion into 6-bromo-l-methyl-j5-carboline the latter was synthesized unambiguously from 5-bromotryptophan and acetaldehyde. The lower melting isomer, recovered in 20% yield, was presumed to be the 8-nitro derivative (254), although this was not established. Nitration of j8-carboline with concentrated nitric acid at 35° has been reported to yield 6-nitro-j3-carboline (253 R = H) as the sole product. Only the 6-nitro derivatives (255) were isolated on nitration... 

One major recent development in the area of natural products is the discovery and subsequent medicinal application of the toxic peptides from cone snails. These Conus peptides, several of which contain a 6-bromotryptophan amino acid, are finding utility for the treatment of neuropathic pain and other neurological conditions (1074-1078). For example, oo-conopeptide MVIIA (Ziconotide, trade name Prialt) has been approved by the US FDA since 2004 for the treatment of severe pain. It is estimated that the 500-700 species of cone snails (Conus genus) contain... 

Lirazan MB, Craig AG, Shetty R, Walker CS, Olivera BM, Cruz LJ (1999) Multiple Bromotryptophan and y-Carboxyglutamate Residues in a Conus Peptide. Philippine J Sci 128 239... 

Taylor SW, Kammerer B, Nicholson GJ, Pusecker K, Walk T, Bayer E, Scippa S, de Vincentiis M (1997) Morulin Pm A Modified Polypeptide Containing TOPA and 6-Bromotryptophan from the Morula Cells of the Ascidian, Phallusia mammillata. Arch Biochem Biophys 348 278... 

Jimenez EC, Watkins M, Olivera BM (2004) Multiple 6-Bromotryptophan Residues in a Sleep-Inducing Peptide. Biochemistry 43 12343... 

A lipophilic tripeptide, janolusimide (342), was isolated from the Mediterranean nudibranch Janolus cristatus and was found to be toxic to mice (260). From the Swedish sponge Geodia baretti barettin, a cyclic polypeptide, was isolated and found to show inhibiting activity on electrically induced contractions of isolated guinea pig ileum (261). Barettin is composed of dehydro-6-bromotryptophan and proline. The initial proposed... 

The majority of conotoxin structures (115 of 125 structures in the PDB) have been determined by NMR spectroscopy as opposed to X-ray crystallography. They have significant structural diversity as a result of their diverse sequences and disulphide connectivities. Furthermore, conotoxins also have a large number of post-translational modifications, including the presence of hydroxyproline, y-carboxyglutamic acid and bromotryptophan residues, epimerisation, glycosyla-tion and amidation,144,145 that enhance their structural diversity. A recent analysis of NMR data for the unusual amino acids present in conotoxins3 provides a reference source for chemical shifts of post-translationally modified amino acids. 

Radiotracer experiments were used to elucidate the biosynthetic precursors to eudistomin H (7) and I (8) in Floridian collections of Eudistoma olivaceum. Both radiolabeled tryptophan and proline were incorporated by E. olivaceum into eudistomins H and I and tryptamine was incorporated into eudistomin I, to the exclusion of eudistomin H. Bromotryptamine and bromotryptophan are incorporated into eudistomin H (Scheme 30). These results suggest eudistomin biosynthesis proceeds from the amino acids via decarboxylation, halogenation, then condensation with proline. 

The recently detected FADH2-dependent halogenases are substrate specific. Tryptophan 7-halogenase catalyzes the chlorination and bromination of d- and L-trypto-phan to 7-chloro- or 7-bromotryptophan, respectively1201. This enzyme also accepts a number of other indole derivatives such as tryptamine, indole-3-acetonitrile, 3-me-thylindole and 5-methylindole as substrates (Fig. 16.9-3a) 43L In addition to indoles, aminophenylpyrrole derivatives are also chlorinated by tryptophan 7-halogenase (Fig. 16.9-3b) 43L... 

Yokoyama and co-workers installed a 4-prenyl group by Heck reaction of fert-prenol (119) with 4-bromotryptophan (280), which was synthesised from... 

The antibiotic tryptanthrin (53) has been biosynthesized from 1 mol of tryptophan and 1 mol of anthranilic acid. Upon feeding tryptophan and substituted anthranilic acids, or substituted tryptophans and anthranilic acid, the expected derivatives of 53 were isolated. The enzymes involved in the biosynthesis of 53 had no specificity for these substrates, with the exception of bromotryptophan. The anthranilic acid moiety used during biosynthesis results from tryptophan degradation 131,172). 

Ala = Alanine, 6-Br-Trp = 6-bromotryptophan, Dide-Phe = a,P-dide-hydro-3,4,5-trihydroxyphenylalanine, Dide-Val = a,P-didehydro-valine, diOH-Sty = 3,4-dihydroxy-trans-styrylamine = [( )-l-amino-2-(3,4-dih-ydroxyphenyl)ethene], Gly = Glycine, lieu = Isoleucine, Leu = Leucine, N-Me = A-methyl, N,N-diMe = A,A-dimethyl-, P-OH = P-hydroxy, OH-Sty = 4-hydroxy-tra s-styrylamine = [( )-l-amino-2-(4-hydroxypheny-l)ethene], Phe = Phenylalanine, Phe-Et = Phenylethylamine, Pro= Proline, Sty = Styrylamine, Trp = Tryptophan, Tyr = Tyrosine, Val = Valine. 

Yokoyama Y, Hikawa H, Mitsuhashi M, Uyama A, Murakami Y (1999) Syntheses Without Protection a Three-step Synthesis of Optically Active Qavicipitic Acid by Utilizing Biomi-metic Synthesis of 4-Bromotryptophan. Tetrahedron Lett 40 7803... 

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