Tryptamines brominated

The medicinal importance of 2-aryltryptamines led Chu and co-workers to develop an efficient route to these compounds (130) via a Pd-catalyzed cross-coupling of protected 2-bromotryptamines 128 with arylboronic acids 129 [137]. Several Suzuki conditions were explored and only a partial listing of the arylboronic acids is shown here. In addition, boronic acids derived from naphthalene, isoquinoline, and indole were successfully coupled with 128. The C-2 bromination of the protected tryptamines was conveniently performed using pyridinium hydrobromide perbromide (70-100%). 2-Phenyl-5-(and 7-)azaindoles have been prepared via a Suzuki coupling of the corresponding 2-iodoazaindoles [19]. 

Several new brominated tryptamines and tryptophans have been described. The Tasmanian bryozoan Amathia convoluta contains convolutindole A (1342) (1319), and the North Sea bryozoan Flustra foliacea (Fig. 3.19) has afforded deformylflustrabromine B (1343) (1320), 1344, 1345, and deformylflustrabromine... 

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... 

Tributylprenylstannane can also attack 3-brominated 2-oxindoles, as exploited by Fuchs and Funk in their synthesis of rac-flustramine A (188, Scheme 36) [154]. After preparation of 3-bromoindolin-2-one 186 from the tryptamine derivative 185, prenylstannane 86 acts as a nucleophile introducing the ferf-prenyl group at C3 affording 187. After three more steps, rac-flustramine A (188) was obtained. 

Dihydroindoles are readily produced from tryptamine and tryptophan derivatives through cycli-zation of amino groups at the indole C-2. This process can be reversed to regenerate the indole after advantage has been taken of the indoline reactivity. For instance, the tryptophan ester (341) can be cyclized to the indoline (342), which can then be brominated at C-5 the product (343) can also be converted to 5-cyanotryptophan (344) (Scheme 108) <92TL29>. The related indoline (3 ) has been... 

Macor and co-workers explored the Mori-Ban reaction to synthesize several antimigraine analogs of Sumatriptan and homo-tryptamines as potent and selective serotonin reuptake inhibitors.The second bromine on substrate 25 was not significantly deleterious to the reaction although a small amount of the 7-bromoindole 26 might be sacrificed at the end of the reaction to consume the active palladium catalyst. This approach to 7-bromoindole 26 can provide a general method accessing 7-bromoindoles, which then could be further manipulated for the synthesis of more complex 7-substituted indoles. 

Tangutorine To prepare aza-cycloaddition substrate 378, tryptamine 371 was diprotected and brominated so that an ensuing Heck coupling would provide ester 377 in 82% yield (Scheme 12.93). Further synthetic manipulations, including condensation with 1,3-cyclohexanedione 106,... 

Like many other marine organisms, dendroceratid sponges contain brominated pyrrole derivatives, many of which derive from tryptamine, with or without a bromine atom at position 5. 

Ircinals A and B, which have already been mentioned with regard to manzamines (see above), isolated from Ircinia sp., may be intermediates in the biosynthesis of manzamines (Kondo et al, 1992a). Several indolic derivatives, often brominated, have been isolated from dictyoceratid sponges of several genera. These metabolites, which are derived from tryptophan or tryptamine, are common in the marine environment and are related to several neuromediators, such as serotonin (5-... 

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