C O M M U N I C A T I O N S
Scheme 2
In summary, allyl selenide 3 is a stable, remarkably effective
procatalyst that generates the unusual cyclic seleninate ester 9 by
a series of oxidation and sigmatropic rearrangement steps upon
reaction with TBHP. The novel heterocycle 9 is significantly more
effective in catalyzing the reduction of TBHP than previously
studied GPx mimetics such as 1 and 2, or the selenocysteine
analogue 4. The relatively poor catalytic activity of selenenyl sulfide
12 in Scheme 2 is in striking contrast to the key role of the
corresponding species in Scheme 1 and in the reduction of TBHP
with BnSH mediated by 2. These experiments also demonstrate
that Se-O compounds can be even more effective than the more
commonly studied Se-N derivatives in this regard.
Acknowledgment. We thank NSERC for financial support.
Supporting Information Available: Experimental procedures and
NMR data for isolated compounds (PDF). This material is available
References
(1) (a) OxidatiVe Stress; Sies, H., Ed; Academic Press: London, 1985. (b)
Free Radicals and OxidatiVe Stress: EnVironment, Drugs and Food
AdditiVes; Rice-Evans, C., Halliwell, B., Lunt, G. G., Eds.; Portland
Press: London, 1995.
(2) (a) Free Radicals in Biology; Pryor, W. A., Ed.; Academic Press: New
York, 1976-1982; Vol. 1-5. (b) Free Radicals in Molecular Biology,
Aging and Disease; Armstrong, D., Sohal, R. S., Cutler, R. G., Slater, T.
F., Eds.; Raven Press: New York, 1984.
substituents.15 Thus, 9 is the first example of a simple unsubstituted
monocyclic seleninate ester.
In the next stage of the catalytic cycle (Scheme 2), 9 reacts with
BnSH to produce the thioseleninate 10, followed by further thiolysis
to afford the selenenic acid 11 and BnSSBn.16 Oxidation and
cyclization (or vice versa) of 11 then regenerates the cyclic
seleninate 9. Evidence for this mechanism is based on the following
observations. First, authentic 9 displays even stronger activity
compared to 3 itself in the oxidation of BnSH to BnSSBn with
TBHP (t1/2 ) 2.5 h). Moreover, when 10 mol % of 3 was employed
as the catalyst and the oxidation was allowed to go to completion,
9 remained as the principal selenium-containing product, along with
the selenenyl sulfide 12. Thus, while 3 is rapidly consumed in the
initial stages of the process, 9 is continuously regenerated. Selenenyl
sulfide 12 was prepared independently and was also tested for
catalytic activity in the model system. However, to our surprise, it
displayed considerably lower activity (t1/2 ) 35 h) and is therefore
ruled out as a significant catalyst in Scheme 2. This is noteworthy
in view of the fact that the corresponding selenenyl sulfides proved
to be essential in the catalytic cycles of selenenamide 213 and GPx
(Scheme 1). In the present case, 12 is probably formed by the
reaction of 1116 with BnSH. Indeed, in the absence of TBHP, cyclic
seleninate 9 reacts rapidly with 3 mol of BnSH to afford 12
quantitatively. When authentic 12 was allowed to stand for
prolonged periods with excess TBHP in the absence of the thiol, it
slowly regenerated the cyclic seleninate 9. Thus, in the present
system, formation of 12 represents a deactivation pathway, in which
catalytic activity is eventually restored by the slow oxidation of 12
back to 9.
(3) OxidatiVe Processes and Antioxidants; Paoletti, R., Samuelsson, B.,
Catapano, A. L., Poli, A., Rinetti, M., Eds.; Raven Press: New York,
1994.
(4) (a) Mugesh, G.; du Mont, W.-W.; Sies, H. Chem. ReV. 2001, 101, 2125.
(b) Selenium in Biology and Human Health; Burk, R. F., Ed.; Springer-
Verlag: New York, 1994.
(5) (a) Ganther, H. E. Chem. Scr. 1975, 8a, 79. (b) Ganther, H. E.; Kraus, R.
J. In Methods in Enzymology; Colowick, S. P., Kaplan, N. O., Eds.;
Academic Press: New York, 1984; Vol. 107, pp 593-602. (c) Stadtman,
T. C. J. Biol. Chem. 1991, 266, 16257.
(6) Mugesh, G.; Singh, H. B. Chem. Soc. ReV. 2000, 29, 347.
(7) For examples, see: (a) Mugesh, G.; Panda, A.; Singh, H. B.; Punekar, N.
S.; Butcher, R. J. J. Am. Chem. Soc. 2001, 123, 839. (b) Galet, V.; Bernier,
J.-L.; He´nichart, J.-P.; Lesieur, D.; Abadie, C.; Rochette, L.; Lindenbaum,
A.; Chalas, J.; Renaud de la Faverie, J.-F.; Pfeiffer, B.; Renard, P. J. Med.
Chem. 1994, 37, 2903. (c) Iwaoka, M.; Tomoda, S. J. Am. Chem. Soc.
1994, 116, 2557. (d) Wilson, S. R.; Zucker, P. A.; Huang, R.-R. C.;
Spector, A. J. Am. Chem. Soc. 1989, 111, 5936.
(8) For examples, see: (a) Jacquemin, P. V.; Christiaens, L. E.; Renson, M.
J.; Evers, M. J.; Dereu, N. Tetrahedron Lett. 1992, 33, 3863. (b) Reich,
H. J.; Jasperse, C. P. J. Am. Chem. Soc. 1987, 109, 5549. (c) Erdelmeier,
I.; Tailhan-Lomont, C.; Yadan, J.-C. J. Org. Chem. 2000, 65, 8152.
(9) For examples, see: (a) Engman, L.; Andersson, C.; Morgenstern, R.;
Cotgreave, I. A.; Andersson, C. M.; Hallberg, A. Tetrahedron 1994, 50,
2929. (b) Detty, M. R.; Friedman, A. E.; Oseroff, A. R. J. Org. Chem.
1994, 59, 8245.
(10) For example, see: (a) Kanda, T.; Engman, L.; Cotgreave, I. A.; Powis,
G. J. Org. Chem. 1999, 64, 8161. (b) Engman, L.; Stern, D.; Cotgreave,
I. A.; Andersson, C. M. J. Am. Chem. Soc. 1992, 114, 9737.
(11) For general information, see ref 6. For mechanistic studies, see: (a) Fischer,
H.; Dereu, N. Bull. Soc. Chim. Belg. 1987, 96, 757. (b) Haenen, G. R. M.
M.; De Rooij, B. M.; Vermeulen, N. P. E.; Bast, A. Mol. Pharmacol.
1990, 37, 412. (c) Glass, R. S.; Farooqui, F.; Sabahi, M.; Ehler, K. W. J.
Org. Chem. 1989, 54, 1092.
(12) Mugesh, G.; du Mont, W.-W. Chem. Eur. J. 2001, 7, 1365.
(13) Back, T. G.; Dyck, B. P. J. Am. Chem. Soc. 1997, 119, 2079.
(14) (a) Nishibayashi, Y.; Uemura, S. In Organoselenium Chemistry:
A
Practical Approach; Back, T. G., Ed.; Oxford University Press: Oxford,
1999, Chapter 11. (b) Nishibayashi, Y.; Uemura, S. In Topics in Current
Chemistry: Organoselenium Chemistry; Wirth, T., Ed.; Springer-Ver-
lag: Berlin, 2000; Vol. 208, pp 201-233.
We also tested the 2-hydroxyethyl and 4-hydroxybutyl analogues
of 3 in the BnSH-TBHP system and found half-lives of 7.7 and
9.8 h, respectively (relative to 4.8 h for 3). In the case of the
4-hydroxybutyl analogue, the corresponding novel six-membered
cyclic seleninate ester (1,2-oxaselenane Se-oxide) was also isolated
and characterized. However, the significantly longer half-lives
compared to that observed with 3 indicates that 3 has the optimum
chain length and 9 has the optimum ring size for catalytic activity.
(15) For fused-ring and substituted 1,2-oxaselenolane Se-oxides, see: (a)
Rabelo, J.; van Es, T. Carbohydr. Res. 1974, 32, 175. (b) Kawashima,
T.; Ohno, F.; Okazaki, R. J. Am. Chem. Soc. 1993, 115, 10434. (c)
Lindgren, B. Chem. Scr. 1980, 16, 24. A ∆4-1,2-oxaselenane Se-oxide
ring system is also known: (d) Mock, W. L.; McCausland, J. H.
Tetrahedron Lett. 1968, 391.
(16) (a) Kice, J. L.; Lee, T. W. S. J. Am. Chem. Soc. 1978, 100, 5094. (b)
Kice, J. L.; Purkiss, D. W. J. Org. Chem. 1987, 52, 3448.
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