Other Indoles

Dramacidin (67), a cytotoxic bisindole alkaloid, was isolated from a deep-water (-148 m) Caribbean sponge (Dramacidon sp.) and was found to inhibit the growth of several cancer cell lines 78). Dramacidin (67) contains two tryptamine units and an unoxidized piperazine ring, which had never been found in marine natural products. Dramacidons A (68) and B (69) were isolated from the Pacific Ocean sponge Hexadella sp. collected off the coast of British Columbia. Dramacidon A (68) shows in vitro 

Unique /3-lactam indole alkaloids, namely, chartellines A (77) (87), B (78), and C (79), methoxydechlorochartelline A (80) (88), and chartella-mides A (81) and B (82) (89), were isolated from a marine bryozoan (Chartella papyracea) collected in North Britanny waters. The structure of chartelline A (77) was confirmed by X-ray analysis, and the absolute 

A series of tricyclic indole alkaloids (physostigmine alkaloids) has been obtained from the cheilostome bryozoan Flustrafoliacea (90). In addition, flustramide B (83) and flustrarine B (84) were isolated from this bryozoan (91). Flustrarine B (84) was prepared from previously known fiustramine B (85) (92) via oxidation with hydrogen peroxide. Five fiustramine derivatives, dihydroflustramine C (86) and its N-oxide (87), fiustramine D (88) and its N-oxide (89), and isoflustramine D (90), were isolated from the methylene chloride fraction of the aqueous methanol extract of a Canadian F. foliacea, and these alkaloids were found to be responsible for the antimicrobial activity of the extract (93). Oxidation of dihydroflustramine C (86) and fiustramine D (88) with m-chloroperbenzoic acid afforded the corresponding A-oxides (87 and 88, respectively). 

The marine mollusc Nerita albicilla was found to contain an oxindole alkaloid that was identified as isoteropodine (91), a previously known plant metabolite (94), by extensive NMR spectroscopic techniques (95). Four indole derivatives, named polyandrocarpamides A-D (92-95), were isolated from the colonial ascidian Polyandrocarpa sp. collected in the Philippines (96). 

The absolute configuration of lyngbyatoxin A (105 = teleocidin A-l) and teleocidin A-2 (106), potent tumor promoters isolated from the blue-green alga Lyngbya majuscula or terrestrial Streptomyces mediocidicus, was determined to be (14/ ) and (145), respectively, by chemical degradation including ozonolysis (103). 

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Crystal stmcture data are available for an indole—trinitroben2ene complex (2) and for the lithium and sodium salts in the presence of polyamine Ligands (3). The crystal stmcture of indole itself is evidendy disordered (4). Table 1 gives the and C-nmr assignments in CDCl (5). C-nmr assignments have been tabulated for many other indole derivatives (6). 

At the present time we have not attempted to isolate a-thioisatin, the presumed intermediate in the synthesis of indigo. However, it is immediately apparent that if this intermediate could be isolated or intercepted in situ, then many possibilities would open up for the conversion of this compound directly into other indole derivatives. It is also apparent that it should be possible to carry out the reaction with substituted thioureas. We shall be exploring these possibilities. 

AM1241 (360) exhibited high affinity and selectivity for CB2 [it (CBi) = 280 nM, (CB2) = 3.4 nM]. (360) Dose dependently inhibited experimental neuropathic pain in a spinal nerve ligation-induced tactile and thermal hypersensitivity model [224]. Other indole derivatives bearing sulfonamide moieties on the side chain, such as compound (361), were disclosed [225]. Though 67 derivatives including pyridyl and other heteroaromatics instead of the indole core were listed, no specific biological data were shown. 

A number of other indole derivatives have also been observed to yield CL subsequent to oxidation. Among these is skatole (3-methylindole), which emits light after oxidation by 02 under strongly alkaline conditions [9],... 

Seven groups of these drugs can be separated based on their various chemical f structures (a) lysergic acid derivatives, of which lysergide (LSD) is the prototype (b) phenylethylamine derivatives, of which 3,4,5-trihydroxyphenylethylamine (mescaline) is the prototype (c) indolealkylamines, such as 4-phosphorodi-methyltryptamine (psilocybin) (d) other indolic derivatives, such as the harmine... 

Mg/kg LSD is given at 3 hourly intervals with the animals being tested only after the last injection (32). Cross tolerance has been observed to other indole and phenylalkylamine hallucinogens (11). Similar effects were also reported for other hallucinogens (10) with an order of potency that paralleled that seen in humans (2) that is, the (hallucinogenic) -isomer of LSD was about 10 times as potent as psilocybin and 100 times as potent as mescaline (10). 

This is the most convenient method of preparing indole-3-acetic acid if an agitated autoclave is available. The method can be used to prepare other indole-3-acetic acids from a-hydroxy acids. For example, a-methylindole-3-acetic acid has been prepared by condensing indole with lactic acid. 

To 25 g indole (or 50 g 4-benzyloxyindole or 0.21 M other indole) in 1 L dry ether at 0° add a solution of 50 ml (75 g) oxalyl chloride in 1 L dry ether carefully and with good stirring a little at a time over Vi hour and stir until bubbling ceases (about one-half hour more). Some indoles require a longer reaction time (e.g., 4-Cl-indole requires fifteen hours refluxing) and some will not react (e.g., 4-Br-indole). Add portionwise, carefully with stirring at 0°, a solution of... 

Add a 1 M excess of nitroethylene dropwise to liquid 5-benzyloxyindole (or other indole) on a steam bath over two hours. Cool, filter and recrystallize from methylene chloride-petroleum ether. Hydrogenate at two atmospheres over 10% palladium-carbon... 

The reaction of //-protected dehydroalanine methyl esters (e.g. 56, 59) with other indoles 58 can also be effected to give the corresponding dehydrotryptophans 60, invariably as the Z-isomers [81]. Murakami, Yokoyama and co-workers also studied oxidative couplings of acrylates, acrylonitrile, and enones with 2-carboethoxyindole, 1-benzylindole, and l-benzyl-2-carboethoxyindole and PdCfe and CuCk or Cu(OAc) 2 to give C-3 substitution in 50-84% yields [82, 83]. 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

Psilocybin and psilocin are believed to work through mechanisms similar to LSD and other indole hallucinogens. Similar to LSD, chronic psilocybin in take also down-regulates 5-HT2 receptors, which parallels the development of behavioral tolerance (Buckholtz et al. 1990). 

J. Other indole alkaloids (including andranginine, adina bases, and cinchona... 

Mantle Cell Lymphoma (MCL). Although MCL is considered an indolent lymphoma, the median survival is less than for the other indolent tumors. The disease is primarily nodal however, the peripheral blood is involved in about 25% of cases. The benign counterpart is unknown (S31). 

Jl. Jepson, J. B., Indolylacetyl-glutamine and other indole metabolites in Hartnup disease. Biochem. ]. 64, 14P (1956). 

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