Y. Nagata et al. / Bioorg. Med. Chem. Lett. 10 (2000) 2709±2712
2711
Scheme 2.
Since the overall product yields are up to 90%, the
results are thought to aord the rational background
for the discussion of total reaction mechanism.
Although there must be several pathways to give these
products, one of the supposed reaction mechanisms is as
shown in Scheme 2. It is well known that NO reacts
with O to form N O or NO according to the ratio of
The similar results were reported by Kochi et al. that
hydroquinone was oxidized by catalytic amounts of
NO in the presence of excess amount of oxygen.
2
1
7
In this paper, we described the reaction of PMC and
NO in the presence of various amounts of oxygen to
form the products, four of which were identi®ed and
quanti®ed. It is the ®rst ®nding that the oxidized pro-
ducts were obtained in good yields by the restriction of
the amounts of NO and oxygen. In addition, the pro-
duct distribution was altered by the change of NO/O2
ratio. Our preliminary experiments showed that the
reaction with a-tocopherol gave analogous results pre-
sented in this paper, and these results will be reported in
a near future.
2
2
3
2
NO/O . Thus, based on the stoichiometry, the major
2
reactive species in the reaction are regarded as NO2
(
+N O )+little O (entries 2±4, 7), N O3 (+NO)
2 3 2 2
(
entries 6, 8, 9), NO (entry 10), and NO +O (entries
2 2 2
11±13), respectively, although these reactive species
interconvert with each other in the reaction mixture.
This interconversion is suggested by the fact that the
result obtained from the use of NO (entry 14) was dif-
2
ferent from that in entry 10. The reaction is supposed to
commence with the hydrogen abstraction with NO,
N O or NO to form phenoxy radical 6. The data in
2
3
2
References and Notes
Table 1 show that NO interacts with PMC without the
aid of O , thus NO must have the reactivity toward
2
1
. Packer, L.; Fuchs, J. Vitamin E in Health and Disease;
Dekker: New York, 1993.
. Massey, K. D.; Burton, K. P. Am. J. Physiol. 1989, 256,
H1192.
. Mickle, D. A. G.; Ki, R. K.; Weisel, R. D.; Birnbaum, P.
L.; Wu, T. W.; Jackowski, G.; Madonik, M. M.; Burton, G.
W.; Ingold, K. U. Ann. Thorac. Surg. 1989, 47, 553.
4. Grisar, J. M.; Petty, M. A.; Bolkenius, F. N.; Dow, J.;
Wagner, J.; Wagner, E. R.; Haegele, K. D.; Jong, W. D. J.
Med. Chem. 1991, 34, 257.
PMC to give the phenoxy radical. In the presence of
reactive NO (or N O ), 6 was supposed to be further
2
2
3
2
oxidized by NO (or N O ) to form PMCquinone 2.
2
2
3
When active NOx was decreased, this process must
become slower, and oxygen can substitute for NO to
3
x
oxidize 6, and the reaction pathway is supposed to
change into the formation of PMCred 3 or 4. When the
amount of NOx was lowered further, the oxidation
might proceed via the sole participation of oxygen after
the initial formation of 6. Since 5 was thought to be a
product of Diels±Alder reaction of a quinonoid 10 and
5. Methods in Nitric Oxide Research, Feelicsh, M., Stamler, J.
S., Eds.; John Wiley & Sons: Chichester, 1996.
1
5
6. Wink, D. A.; Mitchell, J. B. Free Radical. Biol. Med. 1998,
2
2
,
the reaction was carried out in the presence of
5, 434, and references cited therein.
. Pfeier, S.; Mayer, B.; Hemmens, B. Angew. Chem., Int.
excess 2, but the yield of 5 was not increased. Therefore,
there must be an alternative pathway to the formation
for 5 other than the one shown in Scheme 2. Even in the
presence of 0.25 equiv of NO, PMC was consumed by
7
Ed. Engl. 1999, 38, 1714.
. Williams, D. H. L. Nitrosation; Cambridge University
Press: Cambridge, 1988.
8
excess O and elongation of the reaction time (entries
2
9. Janzen, E. G.; Wilcox, A. L.; Manoharan, V. J. Org. Chem.
1993, 58, 3597.
10. d'Ischia, M. Tetrahedron Lett. 1995, 36, 8881.
11, 12). These data suggest there is a pathway where
NO might act in a catalytic manner for the oxidation.
2