1343 m, 1239 w, 1163 s, 1089 m, 1032 s, 973 w, 823 m, 663 s; dH
(300 MHz, CDCl3) 2.46 (3H, s, Ar 4-Me), 3.33 (1H, dd, J 10.8,
4.8, HH-5), 3.54–3.60 (2H, m, H-2, HH-5), 3.83 (1H, dd, J 11.7,
2.1, CHHO), 3.92–3.95 (2H, m, H-3, H-4), 4.21 (1H, dd, J 11.7,
3.6, CHHO), 7.36 (2H, d, J 8.1, 2 × Ar H-3), 7.73 (2H, d, J 8.1,
2 × Ar H-2); dC (75 MHz, CDCl3) 21.6 (CH3), 55.7 (CH2), 63.9
(CH2), 66.1 (CH), 69.5 (CH), 73.1 (CH), 127.7 (2 × CH), 129.9
(2 × CH), 132.5 (C), 144.4 (C); (ES) m/z (%) 313 (M + H+ 100%),
the stirring reaction mixture. After the addition of sodium was
complete the reaction was warmed to room temperature and the
liquid ammonia was allowed to evaporate. The crude residue was
dissolved into water and transferred to a round bottom flask,
water was removed under reduced pressure and the resulting crude
material was purified by flash column chromatography on silica
(100% methanol bubbled with NH3) to give 8 (0.0032 g, 38%) as a
clear oil. To aid analysis dilute HCl (aq) was added to the amine in
water until the solution was pH 2–3, affording the hydrochloride
salt of 8; [a]2D0 +26.9 (c = 0.32 MeOH); vmax(solid)/cm−1: 3334 br
(OH/NH), 2901 br, 1599 br, 1408 w, 1102 m, 1026 m, 970 w,
922 m; dH (400 MHz, D2O) 3.38 (1H, dd, J 12.4, 4.0, HH-5), 3.61
(1H, dd, J 12.4, 4.0, HH-5), 3.60–3.62 (1H, m overlapping, H-
3), 3.81 (1H, app td, J 5.1, 4.4, H-2), 3.87 (1H, dd, J 12.0, 5.1,
CHHO), 3.97 (1H, dd, J 12.0, 4.4, CHHO), 4.56 (1H, app q, J
4.0, H-4); dC (100.6 MHz, CD3OD) 50.2 (CH2), 56.9 (CH), 58.7
(CH2), 62.6 (CH), 72.1 (CH); (ES) m/z (%): 133 (M + H+, 100%);
accurate mass (FAB) found 133.0975 (M + H+ C5H13N2O2 requires
133.0977).
+
330 (42, M + NH4 ); accurate mass (FAB) 313.0970 found (M +
H+ C12H17N4O4S requires 313.0971); anal. found C, 46.04; H, 5.02;
N, 17.84; C12H16N4O4S requires C, 46.14; H, 5.16; N, 17.94%.
Data for 33 [a]D20 +5.2 (c = 0.36 MeOH); vmax(CH2Cl2)/cm−1
3269 br (OH), 2101 s (N3), 1599 m, 1328 s, 1268 m, 1151 s, 1089 s,
1031 m, 991 m, 864 m; dH (300 MHz, CDCl3) 2.46 (3H, s, Ar 4-
Me), 3.21 (1H, dd, J 11.4, 4.2, HH-5), 3.47 (1H, ddd, J 6.0, 4.2,
3.9, H-2), 3.87 (1H, dd, J 11.4, 5.4, HH-5), 3.95–4.04 (3H, m, H-3,
H-4, CHHO), 4.26 (1H, dd, J 12.3, 3.9, CHHO), 7.36 (2H, d, J
8.1, 2 × Ar H-3), 7.71 (2H, d, J 8.1, 2 × Ar H-2); dC (75 MHz,
CDCl3) 21.6 (CH3), 51.2 (CH2), 61.2 (CH), 61.9 (CH2), 64.4 (CH),
77.3 (CH), 127.6 (2 × CH), 129.9 (2 × CH), 132.9 (C), 144.4 (C);
(ES) m/z (%) 642 (2 M + NH4 100%), 313 (68, M + H+), 330
+
+
(46, M + NH4 ); accurate mass (FAB) 313.0972 found (M + H+
Acknowledgements
C12H17N4O4S requires 313.0971).
A single crystal of 32 was obtained by recrystallisation from
The authors thank the EPSRC for a DTA studentship (to KLC)
and to J. Fawcett and K. Singh (Leicester) for carrying out the
X-ray crystallographic studies.
CHCl3. Crystal data: C12H16N4O4S, M = 312.35, monoclinic, a =
3
˚
˚
7.539 (4), b = 17.643 (9), c = 11.223 (5) A, U = 1468.1 (12) A ,
T = 150(2) K, space group P21, Z = 4, absorption coefficient =
0.242 mm−1, 10263 reflections measured, 5092 unique (Rint
=
Notes and references
0.1254), absolute structure parameter = 0.17(14). The final wR(F2)
was 0.1542 for all data. CCDC deposition number 656332.§
1 For selected reviews see: E. B. de Melo, A. D. Gomes and I. Carvalho,
Tetrahedron, 2006, 62, 10277; V. H. Lillelund, H. H. Jensen, X. F. Liang
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A. A. Watson, G. W. J. Fleet, N. Asano, R. J. Molyneux and R. J. Nash,
Phytochemistry, 2001, 56, 265; S. Gerber-Lemaire and L. Juillerat-
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3 A. E. Stu¨tz, in Iminosugars as Glycosidase Inhibitors: Nojirimycin and
Beyond, Wiley VCH, Weinheim, 1999.
4 G. W. J. Fleet, S. J. Nicholas, P. W. Smith, S. V. Evans, L. E. Fellows
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5 F. Popowycz, S. Gerber-Lemaire, R. Demange, E. Rodriguez-Garcia,
A. T. C. Asenjo, I. Robina and P. Vogel, Bioorg. Med. Chem. Lett., 2001,
11, 2489; K. Yasuda, H. Kizu, T. Yamashita, Y. Kameda, A. Kato, R. J.
Nash, G. W. J. Fleet, R. J. Molyneux and N. Asano, J. Nat. Prod., 2002,
65, 198.
6 For selected examples see: C. Laroche, J.-B. Behr, J. Szymoniak, P.
Bertus, C. Schu¨tz, P. Vogel and R. Plantier-Royona, Bioorg. Med.
Chem., 2006, 14, 4047; J. H. Kim, M. J. Curtis-Long, W. D. Seo, J. H.
Lee, B. W. Lee, Y. J. Yoon, K. Y. Kanga and K. H. Parka, Bioorg. Med.
Chem. Lett., 2005, 15, 4282; N. Asano, K. Ikeda, M. Kasahara, Y. Arai
and H. Kizu, J. Nat. Prod., 2004, 67, 846.
7 F. Popowycz, S. Gerber-Lemaire, E. Rodriguez-Garcia, C. Shu¨tz and
P. Vogel, Helv. Chim. Acta, 2003, 86, 1914; S. Gerber-Lemaire, F.
Popowycz, E. Rodriguez-Garcia, A. T. C. Asenjo, I. Robina and P.
Vogel, ChemBioChem, 2002, 3, 466; H. Fiaux, C. Schu¨tz, P. Vogel,
L. Juillerat-Jeanneret and S. Gerber-Lemaire, Chimia, 2006, 60, 185;
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sulfonyl)pyrrolidine (34)
10% Palladium on charcoal catalyst (6.3 mg) was added to a
solution of 32 (0.021 g, 0.067 mmol) in THF (4 ml) and water
(2 ml). The mixture was stirred for 3 h under hydrogen at
atmospheric pressure (balloon). The reaction mixture was diluted
with THF (10 ml), filtered and the filtrate was concentrated under
reduce◦d pressure to give 34 (0.018 g, 97%) as a white solid; mp
92–93 C; [a]D20 −62.3 (c = 1.16 MeOH); vmax(CH2Cl2)/cm−1 3284
br (OH/NH), 2924 br, 1597 m, 1492 w, 1455 w, 1333 s, 1182 w,
1152 s, 1089 m, 1010 m, 948 w, 812 m, 659 s; dH (300 MHz, D2O)
2.45 (3H, s, Ar 4-Me), 3.14 (1H, app t, J 5.6, H-3), 3.195–3.26 (2H,
m, HH-5, H-2), 3.49 (1H, d app t, J 9.6, 5.6, H-4), 3.53 (1H, dd,
J 10.5, 5.6, HH-5), 3.75 (1H, dd, J 12.0, 3.6, CHHO), 3.82 (1H,
J 12.0, 5.4, CHHO), 7.43 (2H, d, J 8.1, 2 × Ar H-3), 7.72 (2H,
d, J 8.1, 2 × Ar H-2); dC (75 MHz, D2O) 20.7 (CH3), 53.3 (CH2),
58.8 (CH), 62.0 (CH2), 67.1 (CH), 74.2 (CH), 127.4 (2 × CH),
130.3 (2 × CH), 131.5 (C), 145.8 (C); (ES) m/z (%): 111 (100%),
287 (42, M + H+); accurate mass (FAB) 287.1065 found (M + H+
C12H19N2O4S requires 287.1066).
8 D. Kim, Y. Kim, T. Kim and K. H. Kim, Bioorg. Med. Chem. Lett.,
1996, 6, 643.
(2S,3R,4R)-2-Hydroxymethyl-3-amino-4-hydroxy-pyrrolidine (8)
9 C. Herdeis, A. Aschenbrenner, A. Kirfel and F. Schwabenlander,
Tetrahedron: Asymmetry, 1997, 8, 2421.
10 G. Limberg, I. Lundt and J. Zavilla, Synthesis, 1999, 178.
11 L. Czollner, J. Kuszmann and A. Vasella, Helv. Chim. Acta, 1990, 73,
1338.
The tosylate 34 (0.018 g, 0.064 mmol) was placed in a three
necked flask fitted with a dry ice condenser and dissolved in a
minimal amount of liquid ammonia (ca. 5 ml) at −78 ◦C. Sodium
metal (0.0044 g, 0.19 mmol) was then added portion-wise to
3552 | Org. Biomol. Chem., 2007, 5, 3544–3553
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