Bleomycin as an Oxene Transferase. Catalytic Oxygen Transfer to Olefins

Admixture of oxidants such as iodosobenzene and sodium metaperiodate to solutions of Fe(III)-bleomycin and Cu(II)-bleomycin effected activation of these species. The active complexes thus formed were found to be capable of transferring oxygen to certain olefinic substrates, including cis-stilbene, styrene, norbornene, and cyclohexene. cis-Stilbene was converted to cis-stilbene oxide reasonably efficiently by bleomycin, but trans-stilbene was shown to be a poor substrate for bleomycin-mediated oxidation. The stereoselectivity of olefin oxidation was thus similar to that observed for cytochrome P-450 model systems, a characteristic also found for a number of other bleomycin-mediated transformations. Also analogous to observations made previously for cytochrome P-450 was the bleomycin-mediated N-demethylation of N,N-dimethylaniline and the oxidation of p-deuterioanisole to p-methoxyphenol with concomitant 1,2-migration of deuterium (NIH shift). However, in contrast to cytochrome P-450, which has been reported to induce asymmetry during the oxidation of certain prochiral substrates, bleomycin-mediated oxidation of styrene resulted in the formation of racemic styrene oxide. Also tested for their oxygen-transfer properties were a number of structural analogues of bleomycin, including epibleomycin, isobleomycin, deglycobleomycin, and N-acetylbIeomycin. All of the tested species were found to be capable of effecting oxygen transfer to olefins with the exception of N-acetylbleomycin, which was also the only analogue dysfunctional in DNA degradation. Although investigated in less detail, it was also shown that oxidation of olefins could be achieved with Fe(II)-bleomycin + O₂, provided that a suitable reducing agent was present. The results obtained are consistent with a mechanism in which the same activated species can be derived from suitable metallobleomycins via the agency of 0₂ and reducing agents or oxygen surrogates such as iodosobenzene and periodate.