4- Formyl-7-hydroxyindole

IndtAoquinones. A route to these quinones (5) involves ozonolysis of benzox-azoles such as 1 to provide 2, which undergoes ready dehydration to l-acetyl-4-formyl-7-hydroxyindoles (3). These products undergo deacylation on chromatography on silica gel to provide 4. This 4-formyl-7-hydroxyindole (4) is oxidized by buffered Fremy s... 

The first total synthesis of 87 was published in 1990 (90TL1523). 5-Hydroxyindole (88) was mesylated and then reduced with sodium cyanoborohydride to give an indoline which was brominated to afford the bromoindoline 89 in good yield (Scheme 33). Cross-coupling with ortho-formyl boronic acid under Suzuki conditions, followed by air oxidation of the resulting cyclized product, followed by reduction of the lactam formed with excess Red-Al gave the target compound 87. 

Nucleophilic processes that generate chloroindoles are largely confined to the displacements of oxy functions and Sandmeyer reactions of diazo-nium salts [81 H( 15)547]. A low yield of 2-chloroindole was obtained by a reaction sequence that involved treatment of oxindole with phosphoryl chloride, and then treatment of the Vilsmeier salt with sodium bicarbonate [66JOC2627 86H(24)2879]. It is, however, much better to prepare this compound from 2-lithioindole (92JOC2495). With phosphoryl chloride and dimethylformamide ethyl l-hydroxyindole-2-carboxylate failed to give the expected 3-formyl derivative. Instead there was a 50% yield of the 3-chloro derivative (84CPB3678). Diazonium salts have been used as precursors in... 

In miscellaneous oxidative processes of indoles, two methods for the preparation of 3-hydroxyindoles have been reported. The first approach involves initial Vilsmeier-Haack reaction of indole-2-carboxylates 176 to afford the corresponding 3-formyl analogs 177. Activation of the aldehyde with p-toluenesulfonic acid (PTSA) and Baeyer-Villiger oxidation with m-chloroperoxybenzoic acid (wi-CPBA) then affords high yields of the 3-hydroxy compounds 178 <00TL8217>... 

The products of the base-catalyzed Stobbe condensation of 3-formylindole and of 2-formylpyrroles undergo acid-catalyzed cyclization to yield l-hydroxycarbazole-3-carboxylic esters and 4-hydroxyindole-6-carboxylic esters, respectively (73JPR295, 74JPR386, 76JPR816). The analogous condensation of dimethyl homophthalate with 2-formyl-1-methylpyrrole and with 3-formylindole produces (443 Hetero = l-methyl-2-pyrrolyl, 3-indolyl), (444) and (445) under acidic conditions (76JHC83). 

A preparation of 3-hydroxyindole-2-carboxylic esters (yields 80-90%) involves Vilsmeier-Haack formylation and the Baeyer-Villiger reaction. ... 

The reaction of N-protected 3-formyl and 3-acetylindole with ra-chloroperoxybenzoic acid has been investigated. 1-Benzenesulfonyl-3-formyl and 1-acetyl-3-formyl indoles gave modest yields of 3-indolones via hydrolysis of unstable formate esters. Some of the corresponding 2-hydroxyindol-3-ones were also formed. The 3-acetoxy derivative of 1-benzenesulfonylindole is more stable and was isolated in 80% yield from the oxidation of 3-acetyl-l-benzenesulfonylindole. <94S411>... 

The reductive cyclization of o-nitrophenylacetaldehydes presents the obvious problem in that the formyl group is susceptible to reduction. Nevertheless, several such successful indole ring formations are known. Moreover, the intermediate hydroxylamine can cyclize onto the formyl group to give an A-hydroxyindole. 

A massive phytochemical survey by the U.S. Department of Agriculture [610] has identified a number of useful sources of L-dopa, the most promising being cultivated velvet beans. However, the microbiological hydroxylation of A-formyl-L-tyrosine esters [436] can be duplicated chemically in excellent yield by the use of benzoyl peroxide in chloroform [611]. Reports state that L-dopa from Japanese sources is superior to that from the U.S.A. [612]. Suitability of patients for L-dopa therapy can be assessed by determination of homovanillic acid and 5-hydroxyindole-3-acetic acid levels before and after treatment with probenecid [613, 614]. This drug reduces the outflow of brain monoamine metabolites into the blood and provides an index of the degree of... 

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