Reduction indole nucleus

GEP496340). This approach to construction of the benzo[a/]indole nucleus is extended to the syntheses of their partially hydrogenated derivatives. Thus, 2-nitrotetralin 149 is converted into 1,8-nitrocarbonyl or dimethylaminomethylene derivatives 150 and 151, the reduction of which gives rise to l,3,4,5-tetrahydrobenzo[cc/]indoles 152 and 153 (55JA3334 84TL285). 

Selective reduction of a double bond in the indole nucleus of melatonin using NaBHaCN/CFsCOOH system resulted as 2,3-dihydromelatonin (Fig. 20) with improved antioxidant activity in the model of quenching of DPPH radical as well as in lipoperoxidation induced by the system Fe/ascorbate in rat brain homogenates [144],... 

Quite early in the chemical studies of Wieland and King, evidence accumulated that the calabash curare alkaloids are indole derivatives, and with present knowledge it is possible to correlate the UV-spectra of many of them with one or another of the following related chromo-phores formally derived from the indole nucleus by oxidation, reduction, and substitution, or combinations of these processes. They are the indoline (II), 2-hydroxyindoline and the derived ethers (III), iV-hydroxy-alkylindoline and its ethers (IV), 2-methyleneindoline or 1-vinylindoline (Va or Vb, respectively), indole (VI), oxindole or 1-acylindoline (Vila or Vllb, respectively), -indoxyl (VIII), and /J-carbolinium (IX) systems it is not possible to distinguish with certainty by spectroscopic methods between the chromophores III and IV, between Va and Vb, or between Vila and Vllb. 

Some earlier methods for reduction of pyrrole and indole nucleus (including metal-promoted reduction, hydrogenation and reduction with use hydride sources) have been examined in a recent review <1996TA317>. 

The technique of cyclization of a 1,4,5,6-tetrahydropyridine to an indole nucleus is already familiar (191), and this method was extended to compound 570. Treatment of 570 with boron trifluoride-etherate gave the keto lactam 571 in 62% yield. Thioketalization and Raney nickel reduction gave a lactam (572) which, upon lithium aluminum hydride reduction, gave 2Q-iso-20-deethylaspermidine (573). However, although the initial keto lactam 571 possessed the required C/D cis stereochemistry, under the thioketalization conditions C-20 isomerization occurred to give the more stable C/D trans ring juncture. 

In most of the examples outlined in this section, the radical cyclizations were accompanied by oxidation to re-establish the aromatic indole nucleus however, there are some cases where the 2,3-dihydroindoles (indolines) were isolated. It remains unclear which stmcmral features are required in order to facilitate this oxidation especially under reductive tributyltin hydride conditions. 

Although the N(l) - H compound (55) provides the 3a-alkoxypyrrolo[2,3-fo] indoles such as 99a and 99b upon the reaction with iodine/morpholine in either MeOH or EtOH, their yields are always inferior, accompanied by tar formation, to those of the 1-methoxy compound (35). Compoimd (99b, 96%) is also obtained by the catalytic reduction of 98b. Since the acetylation of 99b provides 95b (95%), all of the structures are correlated and determined im-equivocally. These findings suggest that the presence of the methoxy oxygen at the 1-position on the indole nucleus makes the intermediate (100) more stable than the corresponding immonium salt (101). 

Evidence for the intermediate formation of nitrone species during the carbonylation of nitroarenes in e s-cyclooctene as solvent catalysed by Ru3(CO)i2 have been obtained [14], Moreover, zerovalent palladium species with nitrogen donor ligands have been shown to be active catalysts in the reductive carbonylation of organic nitro derivatives [41]. The hypothesis that an intermediate having the olefinic double bond coordinated to the metal is formed during the catalytic cycle is supported by the steric effect that has been observed in the case of p,p -dimethyl-o-nitrostyrene (7f) as substrate. Moreover, such an intermediate could explain why a pentaatomic indole nucleus is preferentially formed, even when a conjugated double bond is present in the olefinic chain ... 

The indole nucleus is present in various bioactive molecules and many selective protocols for its construction have been developed. Classical methods for the indole synthesis include the Fischer indole synthesis, the Batcho-Leimgruber synthesis from o-nitrotoluenes and dimethylformamide acetals, the Gassman synthesis from N-haloanilines, the reductive cyclization of o-nitrobenzyl ketones, and the Madelung cyclization of A/ -acyl-o-toluidines [42,43]. 

A mechanism for the elimination of the HNB-label from the indole nucleus of a tryptophan residue was proposed, which involves protonation of the indolenine-HNB complex followed by cleavage of the proton-ated complex to yield the unmodified tryptophan residue and a quinone methide, which by solvation yields HNB-OH. The indolenine structure responsible for the elimination reaction was also confirmed by reduction with NaBT4. One mole of tritium was incorporated in the HNB-protein, and after reduction of the C = N— bond by the hydride neither release of HNB-OH nor concomitant reactivation of the enzyme could be effected. 

Ruthenium-based catalysts display some utility for electrophilic amination of heteroaromatic substrates. Che and coworkers have found that [Ru(TTP)(CO)J in combination with PhI=NTs will oxidize arenes such as furan, indole, and pyrrole (Fig. 13) [68]. Reactions occur optimally under the action of ultrasound, a rather unusual addendum to the standard protocol for C-H amination. More intriguingly still, iV,A-ditosylated products are isolated in most instances, a finding that is not easily resolved mechanistically. As the substrate profile for this amination process involves only electron-rich heteroaromatics, aziridination of the arene nucleus would seem a likely step along the reaction coordinate. Interestingly, no amination product is observed when stoichiometric [Ru(TMP)(NTs)2] (TMP = tetra(2,4,-6-trimethylphenyl)porphyrin) is mixed with either furan or /V-phenylpyrrole. though a reduction of the starting Ru(VI) complex to a Ru(IV) species is noted... 

Yet another approach to the Aspidosperma nucleus has been reported by Wenkert and co-workers (242). This approach was modeled along biosynthetic lines, allowing an iminium species in a piperidine ring to be attacked by the nucleophilic indole -position. This concept met with some success when it was demonstrated that treatment of the vinylogous urethane 564 with HBr gave, after borohydride reduction, the spiro derivative 565. Extension of this reaction to the indoleacetic add series was also successful. The chloroester 566, on treatment with methyl nico-tinate, gave a quaternary salt 567 which was reduced to the tetrahydro-pyridine 568. Treatment of the latter with methanolic hydrochloric add... 

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