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to superoxide radical.29–31 Studies are currently under-
way to characterize the catalytic properties of
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In summary, our work with synthetic benzyl hydrodi-
sulfide shows that the persulfide functional group
readily decomposes to yield reduced oxygen species un-
der physiologically relevant conditions.32–40 The cell-
killing properties of reactive oxygen species are well
known.13,41–44 Overall, the findings reported here may
afford a deeper understanding of the mechanisms be-
hind the biological activity of leinamycin and host of
polysulfide-containing natural products such as vara-
cin,4 lissoclinotoxin A,45 diallyl trisulfide,46–48 bis(2-
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Acknowledgment
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29. Previous researchers who examined the ability of polysul-
fides to accelerate the rate of glutathione-mediated reduc-
We thank the National Institutes of Health for financial
support of this work (CA 83925).
tion of cytochrome
c and resazurin have invoked
analogous catalytic cycles.30,31
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This apparent conflict is not altogether surprising given
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11. Compound 2: 1H NMR (250 MHz, CDCl3) d: 7.31 (m,
5H), 3.89 (s, 2H), 2.88 (s, 1H) ppm. 13C NMR (62.9 MHz,
CDCl3) d: 136.6, 129.2, 128.5, 127.4, 44.7 ppm. Com-
pound 3: 1H NMR (250 MHz, CDCl3) d: 7.34 (m, 5H),
3.95 (s, 2H), 3.71 (s, 3H), 3.21 (s, 2H) ppm. 13C NMR
(62.9 MHz, CDCl3) d: 169.8, 136.8, 129.3, 128.5, 127.5,
52.4, 43.2, 40.1 ppm. Rf 0.6, 5:1 hexane/EtOAc. The
properties of this material matched those previously
reported in the literature (Hiskey, R. G.; Carroll; F. I.;
Babb, R. G.; Bledsoe, J. O.; Puckett, R. T.; Roberts, B. W.
J. Org. Chem. 1961, 26, 1152).
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