W-dealkylation

Disposition in the Body. Readily absorbed after oral administration. Metabolised by side-chain oxidation, glucuronic acid conjugation, and W-dealkylation. Up to about 90% of a dose is excreted in the urine, the major urinary metabolite, probenecid acyl glucuronide, accounting for up to 50% of a dose up to 25% of a dose is excreted as hydroxylated and carboxylic acid... 

Fleisher, J.H. and Harris, L.W. Dealkylation as a mechanism for aging of cholinesterase after poisoning with pinacolyl methylphosphonofluoridate, Biochem. Pharmacol., 14, 641, 1965. 

Figure 7.27 Dealkylation on O and S is also a common metabolic pathway which operates by the same mechanism as W-dealkylation. Top an example of 0-demethylation is seen with the antidepressant venlafaxine. Bottom the anesthetic methitural provides...

Enzymatic methylation of homocysteine (HSCHjCHjCHNHjCOOH) by methylcobalamin to give methionine (CH3SCH2CH2CHNH2COOH) was discovered in 1962 by Woods and co-workers, who also noticed the occurrence of a much slower, nonenzymatic reaction giving the same products. Methylcobinamide showed the same activity as the cobalamin in both the enzymatic and nonenzymatic reactions (72, 7/). It was subsequently discovered that HS, MeS , PhS , and w-BuS will dealkylate a variety of methyl complexes [DMG, DMG-BF2, DPG, G, salen, (DO)(DOH)pn, cobalamin] and even ethyl-Co(DMG)2 complexes to give the thioethers, and it was suggested that the reaction involved transfer of the carbonium ion to the attacking thiolate 161, 164), e.g.,... 

Tri-w-butyllead chloride (Bu3PbCl) can be easily prepared either by dealkylation of Bu4Pb by HC1388 or by chlorination of hexabutyldilead, Bu3PbPbBu3389 ... 

Shimabukuro, R.H., W.C. Walsh, G.L. Lamoureux, and L.E. Stafford (1973). Atrazine metabolism in sorghum Chloroform-soluble intermediates in the JV-dealkylation and glutathione conjugation pathways. J. Agric. Food Chem., 21 1031-1036. 

Yokley, R.A. and M.W. Cheung (2000). Analytical method for the determination of atrazine and its dealkylated chlorotriazine metabolites in water using gas chromatography/mass selective detection. J. Agric. Food Chem., 48 450-457. 

Shao, Z.Q., W. Seffens, W. Mulbry, and R.M. Behki (1995). Cloning and expression of the s-triazine hydrolase gene (trzA) from Rhodococcus corallinus and development of Rhodococcus recombinant sbains capable of dealkylating and dechlorinating the herbicide abazine. J. Bacteriol., 177 5748-5755. 

Vandepitte, V., I. Wierinck, P. Devos, M.P. Depoorter, F. Houwen, and W. Verstraete (1994). N-dealkylation of atrazine by hydrogeno-trophic fluorescent Pseudomonads. Water. Air. Soil Pollut., 78 335-341. 

Cai Y, Baer-Dubowska W, Ashwood-Smith MJ, et al. Mechanism-based inactivation of hepatic ethoxyresorufm O-dealkylation activity by naturally occurring coumarins. Chem Res Toxicol 1996 9(4) 729-736. 

Lee, J.S. and W.Y. Choi (2004). Effect of platinum deposits on Ti02 on the anoxic photocatalytic degradation pathways of alkylamines in water Dealkylation and n-alkylation. Environmental Science and Technology, 38(14), 4026-4033. 

Flurazepam (Dalmane) 1 8 15-50 Oxidation /V-dealkylation Hydroxyethylflurazepana flurazepam aldehyde W-desalkylflurazepam ... 

Stanjek, V. and Boland, W. (1998) Biosynthesis of angular furanocoumarins mechanism and stereochemistry of the oxidative dealkylation of columbianetin to an-gelicin in Heracleum mantegazzianum (Apiaceae). Helv. Chim. Acta, 81,1596-607. 

Jacobson M, Levin W, Poppers PJ, Wood AW, Conney AH. 1974. Comparison of the O-dealkylation of 7-ethoxycoumarin... 

As indicated the adsorbed CO can be desorbed or undergo the shift reaction to an extent depending on the catalyst. In kinetic studies, the reaction orders for both toluene and water were almost zero, indicative of strong adsorption of both reactants. Toluene conversion was retarded by the addition of CO, particularly the rupture of the aromatic ring where the benzene ring is w-bonded flat to the surface. The dealkylation which precedes this involves a a-bonded adsorbed toluene compound where the ring is not in the catalyst surface plane. CO competing for the metal surface would impede the formation of the -complex more than the cr-bonded molecule. 

Michel, H.O., Hackley, B.E., Berkowitz, L., List, G., Hackley, E.B., Gillilan, W., and Pankau, M. 1967. Aging and dealkylation of soman (pinacolyl-methyl phosphonofluoridate)-inactivated eel choUnesterase. Archives of Biochemistry and Biophysics, 121 29-34. 

---