LETTER
Synthesis of a Highly Preorganised 2 -Deoxy-spiro-nucleoside
(15) Fleming, I.; Henning, R.; Parker, D. C.; Plaut, H. E.;
1687
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Chem. Res. 1995, 28, 366. (b) Freier, S. M.; Altmann, K.-H.
Nucleic Acids Res. 1997, 25, 4429.
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E. B. Plant Physiology 2000, 123, 427. (b) Cole–Strauss,
A.; Yoon, K.; Xiang, Y.; Byrne, B. C.; Rice, M. C.; Gryn, J.;
Holloman, W. K.; Kmiec, E. B. Science 1996, 273, 1386.
(c) Zhu, T.; Peterson, D. J.; Tagliani, L.; St. Clair, G.;
Baszczynski, C. L.; Bowen, B. Proc. Natl. Acad. Sci. U.S.A.
1999, 96, 8768. (d) Beetham, P. R.; Kipp, P. B.; Sawycky,
X. L.; Arntzen, C. J.; May, G. D. Proc. Natl. Acad. Sci.
U.S.A. 1999, 96, 8774.
Sanderson, P. E. J. J. Chem. Soc., Perkin Trans. 1 1995, 317.
(16) 1 : 1H NMR (500 MHz, CDCl3): = 7.95 (b, 1 H, NH), 7.74
(q, J = 1.0 Hz, 1 H, H-6), 6.38 (dd, J = 8.3 and 1.8 Hz, 1 H,
H-1 ), 4.09 (d, J = 5.3 Hz, 1 H, H-3 ), 3.78 (dd, J = 9.4 and
7.3 Hz, 1 H, H-5 ), 2.85 (ddd, J = 14.4, 8.3 and 5.3 Hz, 1 H,
H-2 ), 1.92 [d, J = 1.0 Hz, 3 H, CH3-C(5)], 1.83 (dd, J =
14.4 and 1.8 Hz, 1 H, H-2’ ), 1.5–2.1 (m, 6 H, H-6 , H-7 ,
H-8 ), 0.97 (m, 18 H, CH3CH2Si), 0.62 (m, 12 H,
CH3CH2Si). The configuration of C-1 was established by
NOE: Both H-1 and H-3 show a strong NOE with H-2 .
No NOE was observed between H-3 and H-6. Furthermore,
a strong NOE was observed between H-3 and H-5 proving
the configuration of C-3 and C-5 given in Scheme 4. 13
C
NMR (125 MHz, CDCl3, as obtained from the HSQC and
HMBC spectra): = 163.7 (C-4), 150.3 (C-2), 137.6 (C-6),
109.7 (C-5), 97.8 (C-4 ), 85.5 (C-1 ), 78.3 (C-5 ), 75.6 (C-3 ),
42.9 (C-2 ), 31.9 and 29.4 (C-8 and C-6 ), 17.9 (C-7 ), 12.4
(CH3-C-5), 6.7 (CH3CH2Si), 4.9 (CH3CH2Si). ESI-MS: 511
(M + H+); 509 (M – H+).
(7) (a) Paquette, L. A.; Bibart, R. T.; Seekamp, C. K.; Kahane,
A. L. Org. Lett. 2001, 3, 4039. (b) Paquette, L. A.; Owen,
D. R.; Bibart, R. T.; Seekamp, C. K. Org. Lett. 2001, 3, 4043.
(8) Niedballa, U.; Vorbrüggen, H. J. Org. Chem. 1974, 39,
3654.
(9) This ee is not sufficient for incorporation of the prepared
nucleosides into oligonucleotides.
(10) (a) Becker, H.; Soler, M. A.; Sharpless, K. B. Tetrahedron
1995, 51, 1345. (b) Allevi, P.; Tarocco, G.; Longo, A.;
Anastasia, M.; Cajone, F. Tetrahedron: Asymmetry 1997, 8,
1315.
1 : 1H NMR (500 MHz, CDCl3): = 8.01 (b, 1 H, NH), 8.00
(q, J = 1.0 Hz, 1 H, H-6), 6.28 (dd, J = 7.8 and 5.5 Hz, 1 H,
H-1 ), 4.23 (dd, J = 5.6 and 3.0 Hz, 1 H, H-3 ), 3.91 (dd, J =
9.5 and 8.3 Hz, 1 H, H-5 ), 2.25 (ddd, J = 12.9, 5.5 and 3.0
Hz, 1 H, H-2 ), 2.11 (ddd, J = 12.9, 7.8 and 5.6 Hz, 1 H,
H-2 ), 1.94 [d, J = 1.0 Hz, 3 H, CH3-C(5)], 1.5–2.1 (m, 6 H,
H-6 , H-7 , H-8 ), 0.97 (m, 18 H, CH3CH2Si), 0.62 (m, 12 H,
CH3CH2Si). The configuration of C-1 was established by
NOE: H-1 shows a strong NOE with H-2 , and H-3 a
strong NOE with H-2 . A weak NOE was observed
between H-3 and H-6. Furthermore, a strong NOE was
observed between H-3 and H-5 proving the configuration
of C-3 and C-5 given in Scheme 4. 13C NMR (125 MHz,
CDCl3, as obtained from the HSQC and HMBC spectra):
= 163.7 (C-4), 150.3 (C-2), 136.6 (C-6), 109.7 (C-5), 95.7
(C-4 ), 84.4 (C-1 ), 76.9 (C-5 ), 74.4 (C-3 ), 41.8 (C-2 ), 31.4
and 29.2 (C-8 and C-6 ), 17.8 (C-7 ), 12.4 (CH3-C-5), 6.7
(CH3CH2Si), 4.9 (CH3CH2Si). ESI-MS: 511(M + H+); 509
(M – H+).
(11) Ee’s were determined by chiral HPLC (Chiralcel OD-H); for
analytical purpose, the enantiomer of 4 was prepared with -
AD-mix.
(12) Ee of 9 was not determined.
(13) Literature precedent in a related system suggested that
NaBH4 would result in chemoselective reduction of the
epoxide at C(2 ) along with reduction of the lactone to the
lactol. Inspection of the 13C NMR data presented by the
authors, however, indicates that their results were
misinterpreted: Ortuno, R. M.; Cardellach, J.; Font, J. J.
Heterocycl. Chem. 1987, 24, 79.
(17) Hehre, W. J.; Yu, J.; Klunzinger, P. E.; Lou, L. Spartan;
Wavefunction, Inc.: Irvine, CA, 1991.
(18) Grzeskowiak, K.; Yanagi, K.; Prive, G. G.; Dickerson, R. E.
J. Biol. Chem. 1991, 266, 8861.
(14) Fazio, F.; Schneider, M. P. Tetrahedron: Asymmetry 2000,
11, 1869.
Synlett 2002, No. 10, 1683–1687 ISSN 0936-5214 © Thieme Stuttgart · New York