Indoles brominated

Ha.logena.tlon, 3-Chloroindole can be obtained by chlorination with either hypochlorite ion or with sulfuryl chloride. In the former case the reaction proceeds through a 1-chloroindole intermediate (13). 3-Chloroindole [16863-96-0] is quite unstable to acidic aqueous solution, in which it is hydroly2ed to oxindole. 3-Bromoindole [1484-27-1] has been obtained from indole using pytidinium tribromide as the source of electrophilic bromine. Indole reacts with iodine to give 3-iodoindole [26340-47-6]. Both the 3-bromo and 3-iodo compounds are susceptible to hydrolysis in acid but are relatively stable in base. 

The use of mixtures of trimethylbromosilane and dimethyl sulfoxide to brominate indoles is more successful than analogous chlorinations since the bromine atom increases the rate of transformation of Me2S+OSiMe3 to Me2S+Br and shows a stronger electrophilic character than the chloro intermediate. Sulfonium products do not form in such reactions [89JCR(S)182],... 

Chbani, M. Pals, M. Delauneux, J.M. Debitus, C. (1993) Brominated indole alkaloids from the marine tunicate Pseudodistoma arborescens. J. Nat. Prod., 56,99-104. 

An excellent example of the formation of a six membered ring is the hexabutyldistannane mediated ring closure of the brominated indole derivative shown in 4.1. The first step of the process is the palladium catalyzed exchange of one of the bromines to a tributylstannyl moiety, followed by the closure of the six membered ring in a Stille coupling.1... 

Meridianins, brominated indole alkaloids from the tunicate Aplidium meridianum, show cytotoxicity against LMM3 (murine mamarian adenocarcinoma cell line) with IC5o values of 11.4 jM for meridianin B (25), 9.3 iM for meridianin C (26), 33.9 iM for meridianin D (27), and 11.1 aM for meridianin E (28) [41]. 

The range of brominated indoles now available provides opportunities for convenient... 

Fig. 3.19 Flustrafoliacea, a North Sea bryozoan and a producer of many bromotryptamines and brominated indole alkaloids, such as 1343-1346 (Photo A. D. Wright)...

Reineke N, Biselli S, Franke S, Franke W, Heinzel N, Hiihnerfuss H, Iznaguen H, Kammann U, Theobald N, Vobach M, Wosniok W (2006) Brominated Indoles and Phenols in Marine Sediments and Water Extracts from the North and Baltic Seas - Concentrations and Effects. Arch Environ Contam Toxicol 51 186... 

Ji N-Y, Li X-M, Ding L-P, Wang B-G (2007) Aristolane Sesquiterpenes and Highly Brominated Indoles from the Marine Red Alga Laurencia similis (Rhodomelaceae). Helv Chim Acta 90 385... 

As noted above Amathia alternata contains three brominated indoles, 76-78 as well as the p-phenylethylamlne derivative 78 [32]. The three indole derivatives from A. alternata are clearly related to the other Amathla compounds they are amides from indolylethylamine (rather than phenylethylamlne) and the amino acid valine—once more with additional methylatlon and brominatlon. In this series indolylethylamine is likely to be formed from typtophan in much the same way that phenylethylamlne is derived from phenylalanine in the other Amathia compounds. 

In an earlier investigation of Zoobotryon vertlcillatum obtained at San Diego, California, a brominated indole, 79, and its side-chain N-oxide, 80, were found 133). The same bryozoan is very abundant on... 

Non-brominated indoles also underwent the 2-tert-prenyl migration induced by NBS and methylation of the side chain nitrogen was not necessary. N, Ni,-Dimethyl-2-tert-prenyltryptamine (238) afforded the AAi -dimethylamidinium salt 239, which precipitated from EtOAc (63% yield. Scheme 46). When the side chain was monoformylated, no cyclisation was observed. In the case of AbWb-dimethyl-2-Icrt-prenyltryptamine (240), oxidation with NBS was carried out in acetone for solubility reasons affording 3-bromoindole 242 (21%) via bromoin-dolenine 241, which was observed on NMR control. Loss of the side chain of the 3-bromoindolenine on alkaline work-up can be explained by nucleophilic attack of hydroxide at the imine (3-position. 

From North Sea Bryozoan Flustra foliacea) several, brominated indole alkaloids have been isolated. These include deformylflustramine and flustramine. Deformylfrustrabromine A and deformylfrustrabromine B... 

Under similar reaction conditions, 35 generates many products such as 7-bromo- (59), 2,7-dibromotryptamines (60), 57, 7-bromo- (61), 5-bromo-2-oxindoles (62), 56,2-bromotryptamine (63), and 58, depending on the bromination conditions (entries 1-3). l-Hydroxy-Wh-methoxycarbonyltryptamine (52) shows almost the same results as 35. It should be noted that the ratio of all of the 7-brominated indoles to the total products, observed in the bromination of 1-hydroxyindole derivatives (35 and 52), is much higher than that of the N(l)-H compound (55). 

Newman SG, Lautens M (2010) The role of reversible oxidative addition in selective palladium(0)-catalyzed intramolecular cross-couplings of polyhalogenated substrates synthesis of brominated indoles. J Am Chem Soc 132 11416-11417... 

Halogen-containing compounds are not only produced by man, but also by Nature [1740-1742], A brominated indole derivative - Tyrian purple dye - was isolated from the mollusc Murex brandaris by the Phoenicians. Since that time, more than 1,000 halogenated natural products of various structural types have been isolated from sources such as bacteria, fungi, algae, higher plants, marine molluscs, insects, and mammals [1743], Whereas fluorinated and iodinated species are rather rare, chloro and bromo derivatives are found more often. The former are predominantly... 

Carter GT, Rinehart KL Jr, Li LH, Kuentzel SL, Connor JL (1978) Brominated indoles from Laurencia brongniartii. Tetrahedron Lett 46 4479-4482... 

Ji NY, Li XM, Ding LP, Wang BG (2007) Aristolane sesquiterpenes and highly brominated indoles from the marine red alga Laurencia similis Rhodomelaceae). Helv Chim Acta 90 385-391... 

Amino-A-vinyUndoles have been generated through a palladium-catalyzed process (Scheme 3.138) [148]. The initial step in the process entailed the formal addition of brominated indoles to A-tosylhydrazones to generate a vinylindole species as an... 

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