Brominated tyrosine derivatives

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). 

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... 

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... 

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]. 

Kazlauskas, R., R.O. Lidgard, P.T. Murphy, and R.J. Wells Brominated Tyrosine-Derived Metabolites from the Sponge lanthella basta. Tetrahedron Lett. 21, 2277 (1980). 

Kazlauskas, R., Lidgard, R.O., Murphy, P.T, Wells, R.J., and Blount, J. F. (1981) Brominated tyrosine-derived metabolites from the sponge lanthella basta. Aust.J. Chem., 34, 765-786. 

Sorek, H., Rudi, A., Aknin, M., Gaydou, E., and Kashman, Y. (2006b) Itampolins A and B, new brominated tyrosine derivatives from the sponge lotrochotapurpurea. Tetrahedron Lett., 47, 7237-7239. 

Nishiyama, S., Suzuki, T, and Yamamura, S. (1982) Total synthesis of bastadin-6, a brominated tyrosine-derived metalrolite from sponge lanthella basta. Chem. Lett., 1851-1852. 

Kotoku, N., Tsujita, H., Hiramatsu, A., Mori, C Koizumi, N and Kobayashi, M. (2005) Efficient total synthesis of bastadin 6, an anti-angiogenic brominated tyrosine-derived metabolite from marine sponge. Tetrahedron, 61, 7211—7218. 

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... 

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). 

Similar metabolites which appear to be derived from tyrosine and brominated tyrosine include botryllamides A-D (31-34), which were isolated from brightly coloured styelid ascidians from the genus Botryllus collected in Fiji and in Australia [32]. Botryllamide D was reported to exhibit marginal cytotoxicity after 72 hour exposure to the human colon cancer cell line HCT 116 (IC50 17 pg/mL), but were inactive in vivo. The rubrolides, which were isolated from Riterella rubra [33] may well be derived from precursors similar to the botryllamides, however, the rubrolides are not alkaloids so have been mentioned here only for comparative purposes. 

A similar oxidation of tyrosine derivative 244 with an excess of (diacetoxyiodo)benzene in cold acetonitrile followed by quenching with aqueous sodium bromide furnished brominated spirolactone 246 in 80% overall yield. A plausible mechanism for this reaction involves the iodonium derivative245 as an intermediate product and subsequent substitution of each phenyliodonium group with a bromide anion (Scheme 3.100) [311]. 

Keywords antibacterial, biological activity, cytotoxic, marine brominated alkaloids, marine natural products, nematocidal, organohalogens, pharmaceuticals, tyrosine derived alkaloids... 

Costantino, V., Fattomsso, E., Mangoni, A., and Pansini, M. (1994c) Three new brominated and iodinated tyrosine derivatives from lotrochota birotulata, a non-Verongida sponge. /. Nat. Prod., 57, 1552-1556. 

During the past few years several reports have appeared which describe the occurrence of btomocompounds also in sponges and now the Porifera phylum appears as one of the richest sources of bromine-containing metabolites. The next subsection considers the tyrosine-derived bromo compounds the bromopyrrole derivatives and miscellaneous metabolites are reviewed in subsection 1.2. 

Af -2,2-Bis(ethoxycarbonyl)vinyl-protected amino acids are prepared by reaction of commercially available diethyl 2-(ethoxymethylene)malonate (127) with the respective amino acid in methanolic KOH. This rapid reaction is complete within 5 minutes and leads to the potassium salts. Subsequent acidification with 1M HCl yields the amino acid derivative in 75-90% yield.f This intermediate enamine-type N-protection is of particular interest in chemistry to be performed on the carboxy groups of the amino acids such as esterification with alkyl bromides in the presence of a base. Since cleavage of the enamine entity is achieved by treatment with bromine in chloroform at room temperature, it cannot be used for amino acids sensitive to halogenation such as tyrosine, tryptophan, and methionine (Scheme 61). Based on the experience gained with the enamine-type protection the Al-2-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) and N-2-(4,4-dimethyl-2,6-dioxocyclohex-ylidene)isovaleryl derivatives were developed as specific side-chain protecting groups (see Section 2.1.2.2.5.2). 

All of the Amathia brominated amides are presumably biosynthesised from amino acids by similar pathways in the related bryozoans. The amathamides are amides derived formally by reaction of 2-(2,4-dlbromo-5-methoxyphenyl)ethanamlne, 68, with proline followed variously by introduction of a double bond, or methyl, methoxy or bromine substituents. The A. convoluta metabolites 70-74, and 75 from A. alternata are all also derived formally from 2-(2,4-dibromo-5-methoxy-phenyDethanamlne, 68—either by direct amide formation with tyrosine, or by having an additional aminopropyl group which is then... 

Dehalogenation. The NBS-mediated radical side-chain bromination of (V,(V-di-ierf-butoxycarbonyl-protected phenylalanine, tyrosine, histidine, or tryptophan and subsequent treatment with AgNOs in acetone provide the frans-oxazolidinones predominantly, which are then converted to the 8-hydroxy amino acid derivatives in excellent overall yield. a-Bromo esters can be transformed to nitrate esters by treatment with AgNOs in acetonitrile. The subsequent oxidation with NaOAc/DMSO gives the corresponding glyoxylate esters. This strategy has been successfully applied into the total synthesis of macrocyclic (+)-brefeldin... 

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