Achintya K. Sinhababu

Silica gel-assisted reduction of nitrostyrenes to 2-aryl-1-nitroalkanes with sodium borohydride

Abstract Reduction of a variety of nitrostyrenes with sodium borohydride in the presence of silica gel in a mixture of chloroform and 2-propanol furnished the corresponding nitroalkanes free of dimers in near quantitative yields.

Molecular mechanism of biological action of the serotonergic neurotoxin 5,7-dihydroxytryptamine

5,7-Dihydroxytryptamine (5,7-DHT) is a selective serotonergic neurotoxin by virtue of its selective uptake into 5-hydroxytryptamine neurons and its ability to undergo autoxidation. The mechanism by which 5,7-DHT induces neurodegenerative effects remains enigmatic. The mechanism of autoxidation of 5,7-DHT, which has been recently discovered, is unique among the autoxidizable neurotoxins and involves incorporation of oxygen to produce the 4-hydroperoxy-5-keto derivative of 5,7-DHT and thence the (4,7) p-quinone of 4,5,7-trihydroxytryptamine (4,5,7-THTQ), a relatively unreactive quinone. In addition, no reduced oxygen species such as hydrogen peroxide, superoxide and hydroxyl radical are produced during autoxidation of 5,7-DHT. Yet, there is evidence to suggest that both the covalent modification of endogenous macromolecules by 5,7-DHT derived products and the toxic effects of reduced oxygen species are, at least in part, responsible for the neurodegenerative effects of 5,7-DHT. Here we propose that (1) the 4-hydroperoxy-5-keto derivative of 5,7-DHT may serve as a substrate for glutathione peroxidase to eventually produce reduced oxygen species and 4,5,7-THTQ, (2) 4,5,7-THTQ may undergo redox cycling thereby generating reduced oxygen species and lowering the reducing equivalents of the neuron, (3) rapid oxygen consumption by 5,7-DHT and the products derived from it may lead to hypoxia, and (4) the product of autoxidation of 5,7-dihydroxyindole-3-acetaldehyde, the monoamine oxidase metabolite of 5,7-DHT, may serve as an alkylating (crosslinking) agent of proteins.

Selective Ring Omethylation of Hydroxybenzaldehydes Via Their Mannich Bases

Abstract In connection with our synthesis of analogs of serotonin neuro-toxins1 we needed access to 4-hydroxy-3-methoxy-5-methylbenzaldehyde (1) in quantities. The only previous method for the synthesis of 1 involved conversion of o-vanillin to 2-hydroxy-3-methoxytoluene followed by formylation using CHCl3/NaOH in 12% overall yield. We thought a more efficient process would result if we could introduce a methyl group selectively in the position ortho to the hydroxyl group of vanillin (2). However, no direct and selective method for introducing a methyl group into a benzene ring containing a hydroxyl as well as an aldehyde group has been described in the literature. In this paper we describe the development of a method for the synthesis of 1 from vanillin (2) without requiring the protection of either the hydroxyl or the aldehyde function and demonstrate the generality of such a method.

tert-Butyldimethylsilyl ethers of phenols: their one-step conversion to benzyl or methyl ethers and utility in regioselective ortho lithiation

Abstract A new method for the one-step conversion of tert -butyldimethylsilyl ethers of phenols to benzyl or methyl ethers and the blocking effect of the tert -butyldimethylsilyloxy group in regioselective ortho lithiation are described.

Aromatic hydroxylation. Hydroxybenzaldehydes from bromobenzaldehydes via reaction of in situ generated, lithiated .alpha.-morpholinobenzyl alkoxides with nitrobenzene

A general method for the onestep conversion of bromobenzaldehydes to the corresponding hydroxybenzaldehydes has been developed. The method involves in situ protection of the aldehyde function of the bromobenzaldehyde as ita lithium morpholinoalkoxide, followed by lithium-bromine exchange, reaction with nitrobenzene at -75 “C, and a subsequent acidic workup. The method has been applied to the synthesis of 4,5-dimethoxy-3-hydroxy(la), 3,5-dimethoxy-2-hydroxy(2a), 3,5-bis(benzyloxy)-2-hydroxy(2b), 3,4-dimethoxy-2-hydroxy(14), 3hydroxy-4,5-(methylenedioxy)(16), and 4,5-dimethoxy-2-hydroxybenzaldehydea (18) from the bromobenzaldehydes 4, 12a, 12b, 13, 15, and 17, respectively.

An Efficient Method for the Conversion of Phenolic Mannich Bases to C-Methylated Phenols. Synthesis of 3,6-Dimethylcatechol

Abstract In connection with our synthesis of analogs of serotonin neurotoxins1 we needed access to 3,6-dimethylcatechol (1) in quantities. This deceptively simple compound is not available commercially and is extremely inaccessible by the existing methods.2–5 One of these methods5 involves conversion of catechol (2) to 3,6-bis(morpholinomethyl)catechol (3) followed by hydrogenolysis using Pd/C as the catalyst. The latter step required high temperature, long reaction time and a very high catalyst (10% Pd/C) to substrate ratio (1:3 by wt.). In addition, this procedure of hydrogenolysis gave highly variable results in our hands. The difficulty encountered in the conversion of 3 to 1 is not an isolated case. Resistance of phenolic Mannich bases to direct hydrogenolysis is a general6–10 phenomenon although the exact reason for such resistance is not known and no general solution for this problem has been developed. It has been suggested8 that intramolecular hydrogen bonding between phenolic OH and the nitrogen...