LETTER
First Allenic Sulfone to Alkylate Deoxyadenosine
2149
adenosine was reacted with 12 in CH2Cl2 at room
temperature for 28 hours to obtain 21 in 68% yield. In this
case also the product was stable enough to withstand all
purification conditions. After full characterization, 21
[HRMS (FAB+): m/z calcd for C34H38N7O12S [M+H]+:
768.2299; found: 768.2314] was acetylated with Ac2O in
pyridine at room temperature for 15 hours to furnish 20 in
88% yield (Scheme 3).17
References
(1) Present address: New River Pharmaceuticals, 1861 Pratt
Drive, Suite 1090, Blacksburg, VA 24060, USA.
(2) For a discussion on the importance of alkylating agents in
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Chemistry of Drug Design and Drug Action; Elsevier:
Amsterdam, Boston, 2004, Chap. 5. (b) Silverman, R. B.
The Organic Chemistry of Drug Design and Drug Action;
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Scheme 3 Reagents and conditions: (i) a. 2¢-deoxyadenosine,
dioxane, r.t., 2 d; b. Ac2O, pyridine, r.t., 15 h (12 → 19 → 20 46%);
(ii) a. 2¢-deoxy-3¢,5¢-di-O-acetyladenosine, CH2Cl2, r.t., 28 h, 68%; b.
[see (i), b.], 88%.
(10) (a) Nicolaou, K. C.; Wendeborn, S.; Isshiki, K.; Zein, N.;
Ellestad, G. Angew. Chem., Int. Ed. Engl. 1991, 30, 418.
(b) Dai, W.-M.; Chow, C. W.; Zhou, L.; Ishii, A.; Lau, C.
W.; Li, Q.; Hamaguchi, W.; Nishimoto, S.-I. Bioorg. Med.
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Hoster, B. C.; Kerwin, S. M. Bioorg. Chem. 2000, 28, 98.
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In conclusion, we have reported the first synthesis of an
allenic sulfone-modified reactive nucleoside. The reac-
tion pattern of 12 with various nucleophiles is dependent
on the properties of the nucleophiles used. It should be
noted that all allenic sulfones reported so far reacted ex-
clusively with guanine residues of DNA10 and the product
of the reactions between propargyl sulfone-modified
naphthalene and adenine was not stable enough for isola-
tion.10a We have established for the first time that it is in-
deed possible to isolate a stable product from the reaction
between at least one allenic sulfone carrying organic
molecule 12 and the adenine residue of deoxyadenosine.
Using different nucleoside and carbohydrate derived pro-
pargylic sulfones, the impact of the sugar moiety of the
nucleoside on the properties of allenic sulfone group as an
alkylating agent is currently under investigation.
(11) Herdewijn, P.; Balzarini, J.; Baba, M.; Pauwels, R.;
Aerschot, A. V.; Janssen, G.; Clercq, E. D. J. Med. Chem.
1988, 31, 2040.
(12) Compound 9: 1H NMR (360 MHz, CDCl3 + D2O): d = 7.55
(s, 1 H, H-6), 6.13 (dd, J = 4.7, 7.0 Hz, 1 H, H-1¢), 4.06–3.96
(m, 2 H), 3.87 (dd, J = 2.6, 11.9 Hz, 1 H), 3.73 (q, 1 H,
J = 7.9 Hz), 3.36 (m, 2 H, SCH2), 2.65 (m, 1 H), 2.51 (m, 1
H), 2.32 (t, J = 2.6 Hz, 1 H, acetylenic), 1.91 (s, 3 H, CH3).
13C NMR (90 MHz, CDCl3): d = 164.2, 150.5, 136.6, 110.7,
85.5 (C-1¢), 85.5 (acetylene), 79.6 (C-4¢), 72.0 (acetylene),
61.3 (C-5¢), 40.9 (C-3¢), 39.6 (C-2¢), 19.4 (SCH2), 12.4
(CH3). HRMS (FAB+): m/z calcd for C13H17N2O4S [M + H]+:
297.0909; found: 297.0911.
Acknowledgment
TP thanks the Department of Science and Technology, New Delhi,
India for a research grant.
Synlett 2004, No. 12, 2147–2150 © Thieme Stuttgart · New York