Bleomycin as an oxene transferase. Catalytic oxygen transfer to olefins

Natesan Murugesan, Sidney Hecht

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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-acetylbleomycin. 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 O2 and reducing agents or oxygen surrogates such as iodosobenzene and periodate.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalJournal of the American Chemical Society
Volume107
Issue number2
StatePublished - 1985
Externally publishedYes

Fingerprint

Bleomycin
Alkenes
Olefins
Oxygen
Oxidation
Stilbenes
Styrene
Cytochrome P-450 Enzyme System
Reducing agents
styrene oxide
Reducing Agents
Substrates
Stereoselectivity
Oxides
Deuterium
Oxidants
oxene transferase
DNA
Chemical activation
Sodium

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Bleomycin as an oxene transferase. Catalytic oxygen transfer to olefins. / Murugesan, Natesan; Hecht, Sidney.

In: Journal of the American Chemical Society, Vol. 107, No. 2, 1985, p. 493-500.

Research output: Contribution to journalArticle

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