Dermal exposure to cumene hydroperoxide (CumOOH) during manufacturing processes is a toxicological issue for the industry. Its genotoxicity, mutagenic action, ability to promote skin tumor, capacity to induce epidermal hyperplasia and aptitude to induce allergic and irritant skin contact dermatitis are well known. These toxic effects appear to be mediated through the activation to free radical species such as hydroxyl, alkoxyl and alkyl radicals characterized basically by electron paramagnetic resonance (EPR) and spin-trapping (ST) techniques. To be a skin sensitizer CumOOH needs to covalently bind to skin proteins in the epidermis to form the antigenic entity triggering the immunotoxic reaction. Cleavage of the O-O bond allows formation of unstable CumO • /CumOO • radicals rearranging to longer half-life specific carbon-centered radicals R • proposed to be at the origin of the antigen formation. Nevertheless, it is not still clear which R • are precisely formed in the epidermis and thus involved in the sensitization process. The aim of this work was to elucidate in conditions closer to real-life sensitization which specific R • are formed in a 3D reconstructed human epidermis (RHE) model by using 13 C-substituted CumOOH at carbon positions precursors of potentially reactive radicals and EPR-ST. We demonstrated that most probably methyl radicals derived from -scission of CumO • radicals occur in RHE through a one-electron reductive pathway suggesting that these could be involved in the antigen formation inducing skin sensitization. We also describe a coupling between nitroxide radicals and  position 13 C atoms that could be of an added value to the very few examples existing for the coupling of radicals with 13 C atoms.

A one-step access to dithioacetal-α,α-diglycosides is reported. The synthetic strategy is based on the thioacetalization of aldehydes or ketones via highly stereoselective ring-opening of 1,6 anhydrosugars with bis(trimethylsilyl)sulfide.