2640
S. M. Klein et al. / Tetrahedron Letters 49 (2008) 2638–2641
NH2
N
N
NH2
N
N
I
N
N
N
H
N
Cs2CO3, DMF
Scheme 3. Synthesis of 9-butyladenine using freshly made 1-iodobutane.
without adding any additional base. The 3,7-dimethylade-
nine was isolated by using HPLC and C-18 reverse phase
column in 60% yield. The 9-butyladenine was synthesized
by alkylating of a DNA base adenine in DMF using 1-
iodobutane in the presence of cesium carbonate. The puri-
fication of the 9-butyladenine was achieved by double re-
crystallization using toluene then 10% ethanol–water solu-
tion, resulting in a final yield of 51%. Without the second
re-crystallization in ethanol–water, the purity of 9-butylad-
enine was never good. Both compounds were characterized
using 1D NMR and 2D NMR (Figs. 2 and 3 for 3,7-dime-
thyladenine and 9-butyladenine, respectively). The 3,7-
dimethyladenine will continually be used in the study of
the DNA repair proteins, such as AlkB1,11 and TAG.12
The 9-butyladenine will be used to inhibit enzymes, such
as kinase p38 gamma.31 The biological investigations using
3,7-dimethyladenine and 9-butyladenine are on the way.
In summary, a novel and simple method for the prepa-
ration of fresh alkyl halides is reported from the readily
available alcohols and hydriodic acid. This method should
find wide application in organic synthesis and drug discov-
ery, using the alkyl iodides to make a variety of chemicals
as drugs to treat many deadly human diseases. The alkyl
iodides will also be very useful in chemical, biology, and
molecular biology studies.
Fig. 3. NMR (400 MHz) COSY spectrum of 9-butyladenine and a typical
hydrogen to hydrogen correlation.
Acknowledgments
This research is supported by the Office of Research and
Sponsored Programs and Department of Chemistry at East
Tennessee State University. We also thank Dr. Mohseni
for assistance in gas chromatography, and Mrs. Susan
Campbell for error-proof reading.
Supplementary data
Supplementary data associated with this article can be
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