6-Bromo-5-hydroxyindole

Bromo-5-hydroxyindole (176) has been isolated from the midintestinal gland of the muricid gastropod Drupella jragwm from Japan, a predator on corals. It exhibits antioxidative activity, higher than that of a-tocopherol and almost equal to that of BHT [136]. 

Arbidol (ethyl 6-bromo-4-dimethylaminomethyl-5-hydroxyindole-3-carbox-ylate), anew immunomodulator 99KFZ(3)3. 

Snieckus described short syntheses of ungerimine (121) and hippadine by Suzuki couplings of boronic acid 118 with 7-bromo-5-(methylsulfonyloxy)indoline (116) and 7-iodoindoline (117), respectively [130]. Cyclization and aerial oxidation also occur. Treatment of 119 with Red-Al gave ungerimine (121) in 54% yield, and oxidation of 120 with DDQ afforded hippadine in 90% yield. Indoline 116 was readily synthesized from 5-hydroxyindole in 65% overall yield by mesylation, reduction of the indole double bond, and bromination. Indoline 117 was prepared in 67% yield from N-acetylindoline by thallation-iodination and basic hydrolysis. 

The cyclization of IV-allyl-o-haloanilines was adapted to the solid phase for both indoles [332, 333] and oxindoles [334]. For example, as illustrated below, a library of l-acyl-3-aIkyl-6-hydroxyindoles is readily assembled from acid chlorides, allylic bromides, and 4-bromo-3-nitroanisole [332], Zhang and Maryanoff used the Rink amide resin to prepare Af-benzylindole-3-acetamides and related indoles via Heck cyclization [333], and Balasubramanian employed this technology to the synthesis of oxindoles via the palladium cyclization of o-iodo-N-acryloylanilines [334], This latter cyclization route to oxindoles is presented later in this section. 

The on-bead assay was conducted according to Scheme 3.19, which shows the chain of events, which leads to a colorimetric response, when an oligosaccharide binds effectively to the B. purpurea lectin. The lectin was covalently linked to biotin, a small molecule with an extremely high affinity for streptavidin. The bead-lectin-biotin conjugates were then exposed to streptavidin, linked to the enzyme alkaline phosphatase. Alkaline phosphatase hydrolyses phosphate esters [e.g., 5-bromo-4-chloro-3-indolyl phosphate (BCIP), 110]. When the 5-bromo-4-chloro-3-hydroxyindole (111) is released, in the presence of nitro blue tetrazolium (NBT), it forms a dark purple, insoluble dye, thus staining beads where there was a favorable binding interaction. 

CPB3678) and the ester (Table IV) show that these compounds exist entirely as the hydrogen-bonded 1-hydroxy tautomers, but in contrast, 3-bromo-l-hydroxyindole-2-carboxylic acid appears to favor the 3H-indole 1-oxide form [68JCS(C)504]. Only the 1-hydroxy tautomer was observed in a number of cases in deuteriochloroform and in hexadeuterio-dimethylsulfoxide solutions (83JOC3639). 

Hydroxyindole does not exist as such the stable form is the carbonyl tautomer the hydroxy tautomer cannot be detected. There is nothing remarkable about the reactions of oxindole, for the most part it is a typical 5-membered lactam, except that deprotonation at the /3-carbon (p fg 18) occurs more readily than with simple amides, because the resulting anion is stabilised by an aromatic indole canonical contributor. This anion will react with electrophiles like alkyl halides and aldehydes at the /3-carbon, the last with dehydration and the production of aldol condensation products. It is interesting that the 3-position is three times more reactive than the 1-position. Oxindoles can be effectively oxidised to isatins (section 17.14.3) via easy 3,3-dibromination, then hydrolysis. Bromination of oxindole with A -bromosuccinimide gives 5-bromo-oxindole. ... 

Scheme 6, equation 2) [12], The key step in Clive s sequence is the Hoftnann rearrangement of amide 17 to amine 18, followed by oxidation to quinone 19 with phenyliodme(ni) bis(triacetate). In like fashion, 4-bromo-5-hydroxyindole, 5-hydroxy-4-iodoindole, and 5-hydroxy-4-iodo-3-methylindole were prepared in this study. Nishiyama and coworkers adopted an electrochemical oxidation of diaryl amides to carbazoles (equation 3 and 21-22) [13]. 

Kita has described an excellent synthesis of 5-oxygenated indoles viathephenyliodine (III) bis(trifluoroacetate) (PIFA) oxidation of 2-aminoethyl oxygenated phenols (Scheme 2, equations 1 and 2) [5]. This method was extended to the preparation of 5-hydroxyindole, 5-methoxyindole, and 7-bromo-5-hydroxyindole in 65% to 100% yield from the requisite quinone or quinone acetal. 

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). 

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