Chemistry Reference
In-Depth Information
NH
2
NH
2
NH
2
N
N
N
h
ν
N
N
N
+
RO
ROH
N
N
N
N
NH
2
N
3
NH
2
N
N
H
H
H
44
46, 37%
75%
45a, R = Me, 37%
45b, R = Et, 11%
SCHEME 3.27.
indicated earlier in Scheme 3.25, the cross-linking with 8N
3
ATP does not involve the
nitrene nitrogen, but occurs on the opposite side of the adenine ring at the 2-position.
The behavior of 2N
3
ATP is less clear, since there is no electron-donating group to
interact with the nitrene formed from this azide. Even though mechanistic studies for
2-azidoadenosine are lacking, in an earlier study 2-azidoadenine (
) was observed
to undergo the chemistry outlined in Scheme 3.27.
137
While the yields of the alcohol
adducts
44
45a
and
b
are not as high as those observed for
40
, the 8-methoxy adduct
(
45a
) is a signature product for a nitrenium ion intermediate. The companion amine
46
observed in these reactions is typically a product derived from radical hydrogen
abstraction. Therefore, it is likely that
reluctantly forms a nitrenium ion, since the
precursor nitrene has lower basicity than that derived from
44
45
via the corresponding nitrenium ion. A slow rate of nitrene protonation would
provide time for more nitrenes to reach the triplet state and to undergo hydrogen
abstraction to form
40
, and slowly forms
46
. Returning to the creatine kinase study, here again, as with
40
44
and
, cross-linking would not occur at the nitrene nitrogen, but at an electrophilic
site across the adenine ring. Even so, the two isomers of N
3
ATP might very well
become attached to different sites within a protein complex, but if a detailed analysis
of the binding site for ATP were to be done, 8N
3
ATP should become cross-linked
to protein sites close to the 2-position of the adenine ring and 2N
3
ATP to sites
close to the 8-position. Finally all of these correlations are complicated by the fact
that the syn/anticonformations of the adenine ring with respect to the ribose ring
might be altered by the presence of the azide group and the particular protein
environment.
138,139
A further complication encountered with azides such as
, in which the azide
group is attached to a six-membered nitrogen heterocyclic ring, is that an azide-
tetrazole tautomerization occurs as shown in Scheme 3.28. This process has been
studied with 2-azidoadenine
140
and with 2-azidoadenosine monophosphate.
141,142
Two such ring tautomers are possible in the adenine system, and tautomer
44
a
seems to
be favored over tautomer
. The azide form is favored under acidic conditions, and
tetrazole form under basic conditions. In neutral media, both forms are present in
about equal amounts at equilibrium.
138
While both forms might be photoreactive, the
azide seems to be considerably more reactive than the tetrazole form, although both
forms might afford the same reactive intermediate. Here is another area where a
detailed ultrafast mechanistic study would be very informative.
b
