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A. J. Moreno-Vargas, P. Vogel / Tetrahedron Letters 44 (2003) 5069–5073
Table 1. Inhibitory activities of (3S,4S,5R)-5-(2-ammo-
nioethyl)-2,3,4-trihydroxypyrrolidinium dichloride 9 (HCl)2
and its enantiomer 10 (HCl)2. Percentage of inhibition at
1 mM concentration (%), IC50 and Ki in mM, when mea-
sured. Optimal pH, 35°Ca,b
5. For a review about desulfonylation reactions, see: Najera,
C.; Yus, M. Tetrahedron 1998, 55, 10547–10658.
6. Giblin, G. M. P.; Jones, C. D.; Simpkins, N. S. Synlett
1997, 589–590.
7. (a) Wei, Z.-L.; George, C.; Kozikowski, A. P. Tetra-
hedron Lett. 2003, 44, 3847–3850; (b) Wei, Z.-L.;
Petukhov, P. A.; Xiao, Y.; Tu¨ckmantel, W.; George, C.;
Kellar, K. J.; Kozikowski, A. P. J. Med. Chem. 2003, 46,
921–924; (c) Pandey, G.; Tiwari, S. K.; Singh, R. S.;
Mali, R. S. Tetrahedron Lett. 2001, 42, 3947–3949; (d)
Pavri, N. P.; Trudell, M. L. Tetrahedron Lett. 1997, 39,
7993–7996.
8. (a) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993,
34, 7493–7496; (b) Liang, F.; Navarro, H. A.; Abraham,
P.; Kotian, P.; Ding, Y.-S.; Fowler, J.; Volkow, N.;
Kuhar, M. J.; Carroll, F. I. J. Med. Chem. 1997, 40,
2293–2295; (c) Brieaddy, L. E.; Liang, F.; Abraham, P.;
Lee, J. R.; Carroll, F. I. Tetrahedron Lett. 1998, 38,
5321–5322.
9. (a) Popowycz, F.; Gerber-Lemaire, S.; Demange, R.;
Rodr´ıguez-Garc´ıa, E.; Carmona-Asenjo, A. T.; Robina,
I.; Vogel, P. Bioorg. Med. Chem. Lett. 2001, 11, 2489–
2493; (b) Gerber-Lemaire, S.; Popowycz, F.; Rodr´ıguez-
Garc´ıa, E.; Carmona-Asenjo, A. T.; Robina, I.; Vogel, P.
ChemBiochem 2002, 466–470.
Enzyme/inhibitor
9
10
a-Galactosidase
Coffee beans
ni
55%
84%
ni
Aspergillus niger
b-Galactosidase
Escherichia coli
30%
23%
34%
ni
Bovine liver
44%
59%
82%
71%
Jack beans
b-Glucosidase
Almonds
59%
38%
Caldocellum saccharolyticum
a-Mannosidase
Jack beans
97%
97%
IC50=4.8
Ki=2.5 (N)
IC50=4.5
Ki=0.94 (M)
Almonds
98%
98%
IC50=4.9
Ki=1.9 (C)
IC50=4.4
Ki=1.2 (M)
10. Moreno-Vargas, A. J.; Schu¨tz, C.; Scopelliti, R.; Vogel,
P. J. Org. Chem., in press.
11. For examples of reductive elimination using Bu3SnH/
AIBN, see: Padwa, A.; Muller, C. L.; Rodr´ıguez, A.;
Watterson, S. H. Tetrahedron 1998, 54, 9651–9666.
12. Data for (+)-5: [h]D +7 (c 1, CHCl3); 1H NMR (400
MHz, CDCl3, 323 K, l ppm, J Hz) l 7.58 (br. s, 1H,
H-3), 5.61 (br. s, 1H, H-1), 4.59 (d, 1H, J6,7=5.5, H-6),
4.43 (d, 1H, H-7), 4.30 (br. s, 1H, H-5), 2.86 (dd, 1H,
b-Xylosidase
Aspergillus niger
a-N-Acetylgalacto-saminidase
Chicken liver
33%
ni
37%
54%
a For the conditions of measurements, see Ref. 20.
b (C), competitive; (M), mixed type; (N), non-competitive inhibition;
ni, no inhibition at 1 mM concentration.
J4a,4b=18.9, J4a,5=4.4, H-4a), 2.04 (dd, 1H, J3,4b=2.2,
H-4b), 1.48 (s, 9H, (CH3)3C), 1.43, 1.28 (s each, 3H each,
(CH3)2C); 13C NMR (100.4 MHz, CDCl3, l ppm) l 161.7
(C-3), 153.6 (CO), 112.2 ((CH3)2C), 84.2, 83.2 (C-6, C-7),
80.3 ((CH3)3C), 73.9 (C-1), 56.1 (C-5), 34.3 (C-4), 28.3
((CH3)3C), 26.2, 24.7 ((CH3)2C); CIMS 283 (75% [M+
H]+).
Acknowledgements
We are grateful to the Swiss National Science Fonda-
tion (Grant No. 20.63667.00), the ‘Office Fe´de´ral de
l’Education et de la Science’ (Bern, COST D13/0001/
99) and the Direccio´n General de Investigacio´n Cien-
t´ıfica y Te´cnica of Spain (Grant No. BQU-2001-3779)
for generous support. We thank also Miss C. Schu¨tz for
the enzymatic measurements.
1
13. Data for (+)-6: [h]D +50 (c 0.45, CHCl3); H NMR (400
MHz, CDCl3, 298 K, l ppm, J Hz, mixture of two
rotamers) l 5.00, 4.91 (s each, 1H, H-1), 4.73 (d, 1H,
J6,7=5.6, H-6), 4.63 (br. d, 1H, H-7), 4.38, 4.22 (br. s
each, 1H, H-5), 2.93 (dd, 1H, J3a,4a=6.23, J3a,3b=14.7,
H-3a), 2.79 (m, 1H, H-3b), 1.94 (m, 1H, H-4a), 1.50 (s,
9H, (CH3)3C), 1.48 (m, 1H, H-4b), 1.44, 1.35 (s each, 3H
each, (CH3)2C); 13C NMR (100.4 MHz, CDCl3, l ppm,
mixture of two rotamers) l 154.1, 153.6 (CO), 111.3
((CH3)2C), 83.1, 82.5, 82.2, 81.8 (C-6, C-7), 79.9, 79.8
((CH3)3C), 73.4, 72.5 (C-1), 59.5, 58.3 (C-5), 39.1, 39.0
(C-3), 29.3, 29.0 (C-4), 28.4 ((CH3)3C), 26.0 ((CH3)2C),
24.4, 24.3 ((CH3)2C); CIMS 285 (38% [M+H]+).
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