Products of Dithionite Reductive Activation

Dithionite-mediated reductive activation of mitomycin C has been employed in the study of its DNA alkylation chemistry.6,63 However, dithionite activated mitomycin C possesses different DNA alkylation properties than that activated by catalytic hydrogenation and enzymatic reduction. We postulated that a new alkylating species is produced by dithionite reductive activation resulting in different reactivity than the iminium methide species. To investigate dithionite-mediated reductive activation further, we treated 13 C-labeled analogues of WV-15 with dithionite and carried out spectral and product studies. 

Typically, the dithionite species disproportionates in aqueous media to afford the hydrogen sulfite and thiosulfonate nucleophiles.64 This finding suggests that sulfite esters (-0S02 ) and Bunte salts (-SS03-)65 could be formed upon iminium methide 

SCHEME 7.10 Fate of the ene-imine reactive species. The 13C labels are designated with asterisks ( ). 

The above studies show that dithionite reduction of mitosenes results in the formation of lOa-sulfite esters as well as sulfonates. The presence of the excellent sulfite-leaving group at the mitosene 1 Oa-position suggests that alkylation reactions at this position could still occur. The subsequent sulfite to sulfonate rearrangement results in loss of alkylation capability by this position. 

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