Organic Letters
Letter
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isopropylidene ribose 7 failedto reactat all. Benzoylated analogue
8,knowntoprovideaneighboringgroupeffectviaformationofan
acetoxonium ion under Vorbruggen conditions, also failed to
̈
1993, 335, 415.
react to any extent with the nucleobase and only traces of any
reaction occurring at all were evident by TLC and crude NMR
analysis. Reaction with D-arabinose yielded selectively the
predicted α-anomer 9 in 48% yield accompanied by only traces
of the β-anomer (∼2.5%) and the α-furanoside (∼2%) side
products as confirmed by ROESY analysis (see the Supporting
Information). These results suggest that the unprotected,
unhindered C2-OH of the sugar is crucial to dictating the final
stereochemistry either through a directing effect or neighboring
group effect.
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In conclusion, we report a conceptually novel direct
glycosylation strategy for nucleoside synthesis using Mitsunobu
conditions and either unprotected or 5-O-monoprotected ribose.
The reaction of ribose with nucleobases gives preferentially β-
ribopyranosylnucleosidesinmoderatetogoodyield.Themethod
is applicable to both purine- and pyrimidine-based heterocycles,
andtheβ-anomerisformedexclusively. Wethenappliedthesame
conditions to provide purine or pyrimidine β-ribofuranosides in a
one-pot method. This was achieved by coupling the nucleobase
with MMTr-protected D-ribose and subsequent in situcleavage of
the MMTr group. A more in-depth mechanistic study, including
why the anomeric alcohol reacts preferentially, has certainly been
necessitated and has already begun but is beyond the scope of this
communication. Expanding this operationally simple protocol to
include larger nitrogenous heterocycles or modified sugars with
medicinal implications is obvious, and efforts are underway. The
results will be reported in due course.
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ASSOCIATED CONTENT
* Supporting Information
TheSupportingInformationisavailablefreeofchargeontheACS
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Carbohydr. Res. 1982, 108, 298. (b) Igarashi, K. Adv. Carbohydr. Chem.
Biochem. 1977, 34, 243.
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Experimental procedures, analytical data, and comparison
of purine nucleoside yield (PDF)
NMR spectra for obtained compounds (PDF)
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Minton, M.; Bolli, M.; Miculca, C.; Windhab, N.; Micura, R.; Stanek, M.;
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AUTHOR INFORMATION
Corresponding Authors
■
Notes
̌
Naus, P.; Pohl, R.; Votruba, I.; Furman, P. A.; Tharnish, P. M.; Otto, M. J.
J. Med. Chem. 2005, 48, 5869.
(20) Review:(a) Cafferty, B. J.; Hud, N. V. Curr. Opin. Chem. Biol. 2014,
22, 146. Recent example: (b) Singh, P.; Singh, A.; Kaur, J.; Holzer, W.
RSC Adv. 2014, 4, 3158.
(21) Yadav, V.; Chu, C. K.; Rais, R. H.; Al Safarjalani, O. N.; Guarcello,
V.; Naguib, F. N. M.; el Kouni, M. H. J. Med. Chem. 2004, 47, 1987.
(22) Bookser, B. C.; Raffaele, N. B. J. Org. Chem. 2007, 72, 173.
(23) Marasco, C. J.; Pera, P. J.; Spiess, A. J.; Bernacki, R.; Sufrin, J. R.
Molecules 2005, 10, 1015.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Thisworkwassupported bytheASCR(RVO:61388963)andthe
Czech Science Foundation (P207/11/0344 to A.M.D. and
M.H.). We are grateful to M. N. Trung and S. Schmalisch for
their assistance with the project and helpful discussions.
́
̌ ́ ́
(24) Hocek, M.; Holy, A.; Votruba, I.; Dvorakova, H. J. Med. Chem.
2000, 43, 1817.
REFERENCES
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(26)Amore indepthsummaryandcomparisonof theyieldsisprovided
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