Oxidation of Some Biologially Active and Related Sulfur Containing Compounds

Earlier works on oxidation of sulf ides, thiols, and disulf ides with both chemical and enzymic systems are reviewed. Enzymic oxidations of thiols and disulfides are compared with their chemical oxidations with N2O and H2O2 by the use of unsymmetrical disulf ides, thiolsulfinates and O18_ tracer technique. In both enzymic oxidation and that with N2O, oxidation of disulfides to thiolsulfinates is more facile than that of thiolsulfinates to thiolsulfonates, which is presumed to be mainly the end by-products in the oxidation of either thiols or disulf ides to sulfonic acids. INTRODUCTION Many years ago, when we initiated to study the mechanism of the Pummerer reaction of alkyl sulfoxides, we suggested that the rearrangement serves as a likely model pathway of enzymatic oxidative demethylation of methionine, in view of the facile hydrolysis of the resulting ester in the following reaction (Ref.l). )i' WO_Na CH C-O-P H 0 CH3CH3 > CHSCH2OCCH 4 CH3SH + CH2O + CH3COOH 38C,pH5, 1 day Methionine itself was found to give homocysteine similarly (Ref.2). CH2--CH3 çH2sCH2ococH3 çH2SH I (CHC)O ' H CH2 0 3 2 > CH2 CHNH CHNHCOCH Hydrolysis CHNH 2 3 2 COOH COOH COOH The formation of the sulfoxide in the metabolic oxidation was already noticed with 4-(phenylthioethyl)-l,2-diphenyl-3,5-pyrazolinedione (I) by Burns et al. (Ref.3). Evidence, more concrete to support our hypothesis was found by Barnsley and Arnold group (Ref.4) who identified following products (II)-(IV) among rat-urine after subcutaneous injection of S-methylcysteine into rats. Ph COOH POOH /N\, CH3-S-CH2-CH —> CH -$-CH2-CH HO/S-Ph , NH2 HCOCH t N. (II) methylmercapturic CH3SCH2COOH I acid sulfoxide ?OOH CH3SCH2CONHCH2 CH3-S-CH2-CH OOH NHCOCH3 (IV) (III) methylmercapturic N(methylthioacetyl) -glycine aci