low-potential ground-state reductants or oxidants, respec-
tively (AQ, -0.84;7 PTZ, 0.76 V8 vs SCE). Also, AQ labeled
at the 5′-terminal phosphate or at the 2′-position of a
nucleotide in DNA has been previously used for studying
photoinduced oxidative damage in DNA.2a Previous nucleo-
base labeling with redox probes is limited primarily to
substitution at the 5-position of deoxyuridine. A recent report,
although, describes AQ attached to the N6-exocyclic amino
group of adenine.9 This report further substantiates the
usefulness of AQ as a mechanistic charge-transfer probe. In
general, reports of derivatized purines are fewer in number
with only simple alkynyl (e.g., propyne), alkenyl, alkyl, and
amino derivatives being described.10
enosine. The alkynyl PTZ and AQ derivatives were prepared
as shown in Scheme 1. A Michael addition of PTZ to
Scheme 1. Synthesis of PTZ and AQ Alkynes
To minimize the number of chemical transformations while
recognizing the sensitivity of these redox-active chromo-
phores to reducing and oxidizing conditions, a Pd(0)-cata-
lyzed coupling strategy was employed. Several inorganic3d-f,11
and organic12 5-labeled derivatives of uridine have been
recently prepared using the Sonogashira reaction.13 We have
extended this approach to the coupling of redox-sensitive
organic chromophores to the purine nucleoside 2′-deoxyad-
acrylonitrile in the presence of tetrabutylammonium hydrox-
ide produced nitrile 2, and this procedure was a modification
of an earlier method.14 Alkaline hydrolysis yielded the
carboxylic acid 3, and subsequent coupling with propargy-
lamine using DCC/HOBt afforded the PTZ alkyne 4. The
AQ derivative was prepared by first reacting 9,10-an-
thraquinone carboxylic acid with (COCl)2 and DMF (cat.)
to produce the acid chloride intermediate. Next, the addition
of propargylamine and DIEA gave alkyne 6 in good yield.
The syntheses of the labeled 2′-deoxyadenosines are shown
in Scheme 2. The purine nucleoside 8-bromo-2′-deoxyad-
enosine,15 7, was first protected at the 5′-position with
dimethoxytrityl chloride (DMT-Cl) in pyridine to give the
DMT-protected nucleoside 8. Transient protection of 3′-
hydroxyl with excess TMS-Cl in pyridine followed by
addition of benzoyl chloride afforded the N7-benzolyated
intermediate. The TMS group was selectively removed in
cold methanolic ammonia, and following flash chromatog-
raphy, O5-(4,4′-dimethoxytrityl)-N-benzoyl-8-bromo-2′-
deoxyadenosine, 9, was obtained in high yield. The Pd(0)
cross-couplings of 9 with either redox probe 4 or 6 proceeded
smoothly in good yield (Scheme 2). A number of different
catalysts, bases, and reaction conditions were employed to
optimize these reactions.
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