Thiols were effectively oxidized into disulfides by reacting with hydrogen peroxide in the presence of a catalytic amount of iodide ion or iodine.The controlled oxidative coupling of thiols to disulfides is important in organic synthesis, and a wide range of methods have been developed for this transformation. 1 Thiols are among the functional groups which can be easily over oxidized, therefore, extensive studies have been carried out for their controlled oxidation with molecular oxygen, 2 peroxide, 3 metal oxidants, 4 halogens and derivatives, 5 sulfoxide, 6 and N-oxide. 7 In particular, the methods of oxidative coupling of disulfides with halogens such as I 2 , 5a I 2 /HI, 5b and Br 2 /KHCO 3 5c were carried out under mild reaction conditions, and gave the disulfides in good yields. However, these reactions require a stoichiometric amount of oxidants and long reaction times. Oae and co-workers developed the oxidative coupling of thiols to disulfides by dimethyl sulfoxide in the presence of a catalytic amount of molecular iodine. 5b Although this reaction affords the products in high yield under very mild reaction conditions, there are still some problems such as the requirement of a long reaction time and the production of foulsmelling dimethyl sulfide as a waste product.To develop an environmentally benign oxidative coupling of thiols, we planned to use hydrogen peroxide as a cooxidant for the oxidation of thiols with molecular iodine, because the iodide ion (iodoanion) is easily oxidized to molecular iodine by hydrogen peroxide.Hydrogen peroxide itself can oxidize thiols to the corresponding disulfides; however, alkaline conditions were required. 3a Recently, Bégué et al. reported that disulfides can be efficiently prepared from thiols using 30% hydrogen peroxide in fluoroalcohols at ambient temperature under neutral conditions. 3b Although this method provides the desired compounds in high yields in most cases, fluoroalcohols are expensive for industrial use. Furthermore, the thiols, which are less soluble in the fluoroalcohols, produced the desired disulfides in poor yields. In this paper, we describe a method for the oxidation of thiols 1 to disulfides 2 using 30% hydrogen peroxide catalyzed by iodide ion (Scheme 1). Scheme 1

No abstract

No abstract

Purpose: Dihydropyrimidine dehydrogenase (DPD), the initial rate-limiting enzyme in the degradation of 5-fluorouracil (5-FU), is known to be a principal factor in clinical responses to the anticancer agent 5-FU, and various reports have clearly demonstrated that DPD activity is closely correlated to mRNA levels. However, the regulatory mechanisms of DPD gene (DPYD) expression remain unclear. In this study, the regulatory mechanisms have been intensively studied.Experimental Design and Results: A subcloned 3.0-kb fragment of the 5 region of DPYD contains a total of 60 CpG sites, suggesting that methylation status may affect the repression of DPYD. The clone showed various promoter activities that were largely correlated with mRNA levels in most cell lines, except HSC3 and HepG2. Bisulfite sequencing analysis revealed that various CpG sites around the transcription start site were abnormally methylated in cells with low DPYD expression: Reversal of hypermethylation by 5-azacytidine treatment significantly increased DPYD expression in HSC3 and HepG2 cells that showed strong promoter activity. In HepG2, in vitro methylation of the DPYD promoter directly decreased promoter activity, and 5-azacytidine treatment restored higher DPYD expression in a dose-and time-dependent manner, along with decreased sensitivity to 5-FU.Conclusions: We found that DPD activity was controlled, at least in part, at the transcription level of DPYD and that aberrant methylation of the DPYD promoter region acted as one of the repressors of DPYD expression and affected sensitivity to 5-FU in cancer cells. Our new results could lead to a more precise understanding of the molecular basis of 5-FU response.