Organic Letters
Letter
Last, we applied VCD spectroscopy to elucidate the structure
of a pair of L-nucleoside diastereomers 3. Both diastereomers of
3 exhibited the same 3JH1′H2′ coupling constant of 4.3 Hz. Parts
e and f of Figure 4 show the comparison of the theoretical and
experimental VCD spectra. Clearly, the VCD spectra observed
for the major and minor diastereomers exhibited a better
agreement with those calculated for 3β and 3α, respectively.
From these comparisons, the structures of the major and minor
isomers were determined. The VCD results also indicated that
these nucleosides mostly exist as north conformations (Figure
S8), in a similar manner to ribonucleosides and 2′-O-[2-
(alkoxy)ethyl] derivatives.5c
In summary, we synthesized several diastereomeric pairs of
furanose monosaccharides and nucleosides and studied their
structures by VCD spectroscopy. For the first time, this work
demonstrates the effectiveness of VCD spectroscopy in
determining the configurations as well as flexible conformations
of both furanose monosaccharides and nucleosides. The VCD
results for an AZT derivative (1β) clarified its north−south ring
pucker ratio, which is comparable to the ratio estimated by
NMR. Meanwhile, the furanose conformation of a FANA
derivative (2β) was elucidated as an equilibrated state of
unusual east and south/east puckers. Preferred conformations
of a given molecule could be predicted by theoretical
calculations alone; however, it is desirable to examine its
reliability on the basis of experimental data, as different
theoretical methods could yield contradictory results, as is the
case for 6-ribo. Because the configuration and conformation of
the sugar moiety of nucleosides are closely related to their
functions, further use of VCD spectroscopy should advance
studies involving carbohydrate and nucleic acid.
REFERENCES
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ASSOCIATED CONTENT
* Supporting Information
■
(11) (a) Taniguchi, T.; Monde, K. Chem. - Asian J. 2007, 2, 1258−
1266. (b) Sprenger, R. F.; Thomasi, S. S.; Ferreira, A. G.; Cass, Q. B.;
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(c) Taniguchi, T.; Monde, K. J. Am. Chem. Soc. 2012, 134, 3695−3698.
S
The Supporting Information is available free of charge on the
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Predicted conformers, procedures for experiments and
calculations, synthesis, and characterization (PDF)
AUTHOR INFORMATION
Corresponding Authors
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ORCID
́
(f) Gordillo-Roman, B.; Camacho-Ruiz, J.; Bucio, M. A.; Joseph-
Author Contributions
§T.T. and K.N. contributed equally.
Nathan, P. Chirality 2013, 25, 939−951.
(14) Debie, E.; De Gussem, E.; Dukor, R. K.; Herrebout, W.; Nafie,
L. A.; Bultinck, P. ChemPhysChem 2011, 12, 1542−1549.
(15) The following equation was used to estimate the north−south
ratio of 1β (3JH1′H2′ (cis) = 3JH1′H2′ (trans) = 6.3 Hz) by NMR; % south =
Notes
3
100 × (3JH1′H2′ (cis) + JH1′H2′ (trans) − 7.1)/9.
(16) Note that variations in the Boltzmann factors of 10% did not
significantly change the population-averaged spectrum.
(17) This work solely used CDCl3 as solvent, and as of now the
accuracy of VCD theoretical calculations to predict the conformational
behavior of a molecule of interest in aqueous solution is yet to be
improved.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank Prof. Satoshi Ichikawa (Hokkaido University) for
valuable discussions about the synthesis of artificial nucleic
acids and Dr. Rina K. Dukor (BioTools, Inc.) for her generous
support for CompareVOA spectral analysis. This work was
supported by the Japan Society for the Promotion of Science
(JSPS), the Sumitomo Foundation, and the Suhara Memorial
Foundation.
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Org. Lett. XXXX, XXX, XXX−XXX