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the products were in agreement with the proposed struc-
tures 2a,b.12 Studies on their glycosidase inhibitory
activity are in progress and will be reported elsewhere.
In summary, we have developed a simple and concise
synthesis of the trihydroxylated pyrrolidine alkaloids
2a and 2b in an overall yield of 13.7% and 11.5%, respec-
tively, starting from D-glucose.
Acknowledgements
8. (a) Nishimura, Y.; Umezawa, Y.; Adachi, H.; Kondo, S.;
Takeuchi, T. J. Org. Chem. 1996, 61, 480; (b) Wong, C.
H.; Provencrer, L.; Porco, J. A.; Jung, S. H.; Wang, Y. F.;
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60, 1492; (c) Brandi, A.; Cicchi, S.; Takeuchi, T. J. Org.
Chem. 1995, 60, 6806.
We thank the Department of Science and Technology
(SP/S1/G-23/2000) for financial support and the Univer-
sity Grants Commission for a grant to procure a High
Field NMR spectrometer. We are grateful to Prof. M.
S. Wadia for helpful suggestions.
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references cited therein.
References and notes
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Bernardi, A.; Capelli, A. M.; Gennari, C.; Scolastico, C.
Tetrahedron: Asymmetry 1990, 1, 21; (e) Davies, S. G.;
Ichihara, O.; Walters, I. A. S. Synlett 1993, 461; (f)
Castello, J. F.; Davies, S. G.; Garrido, N. M.; Ichihara, O.
Tetrahedron: Asymmetry 1994, 5, 1999; (g) Davies, S. G.;
Garrido, N. M.; Ichihara, O.; Walters, I. A. S. J. Chem.
Soc., Chem. Commun. 1993, 1153; (h) Bunnage, M. E.;
Davies, S. G.; Goodwin, C. J. J. Chem. Soc., Perkin Trans.
1 1994, 2385; (i) Davies, S. G.; Fenwick, D. R. J. Chem.
Soc., Chem. Commun. 1995, 1109; (j) Hawkins, J. M.;
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10. The 1H NMR spectrum of the crude compound 4 showed
the presence of a mixture of E and Z isomers and the
hydrated form of the aldehyde.
11. Procedure for 5a and 5b: To a solution of benzylamine
(0.178mL, 1.63mmol) and acetic acid (0.074mL,
1.30mmol) in dry methanol (6mL) at ꢀ20ꢁC was added
4 (0.5g, 1.63mmol) in methanol (4mL) over a period of
30min under a nitrogen atmosphere. The solution was
stirred at the same temperature for 1h and NaCNBH3
(0.153g, 2.45mmol) was added in three portions (10min).
The mixture was stirred at ꢀ20ꢁC for 2h and allowed to
warm to room temperature. After stirring at room
temperature for 8h, the solution was concentrated under
reduced pressure. Saturated Na2CO3 solution was added
to the residue, the solution was extracted with chloroform
(15mL · 3) and the combined extract was dried over
anhydrous sodium sulfate. Removal of chloroform
afforded a thick oil, which was purified by chromatogra-
phy (pet. ether/ethyl acetate = 9.5/0.5) to gave 5a in 47%
yield and 5b in 34% yield.
12. All new compounds were obtained in analytically pure
25
form. Data for 5a: ½aꢁD 4:45 (c 0.44, CHCl3). IR (neat):
1780.2cmꢀ1 1H NMR (300MHz, CDCl3): d 2.35 (dd,
;
J = 8.2, 9.7Hz, 1H, H-1a), 2.42 (dd, J = 0.8, 18.0Hz, 1H,
H-5a), 2.56 (dd, J = 6.7, 18.0Hz, 1H, H-5b), 3.29 (dd,
J = 6.7, 9.7Hz, 1H, H-1b), 3.40 (dt, J = 0.8, 6.7Hz, 1H,
H-4), 3.42 (d, J = 12.9Hz, 1H, NCH2Ph), 3.79 (d,
J = 12.9Hz, 1H, NCH2Ph), 4.14 (ddd, J = 2.3, 6.7,
8.2Hz, 1H, H-2), 4.54 (ABq, J = 11.7Hz, 2H, OCH2Ph),
4.78 (dd, J = 2.3, 6.7Hz, 1H, H-3), 7.22–7.36 (m, 10H, Ar-
H); 13C NMR (75MHz, CDCl3): d 34.68 (C-5), 57.62,
57.81 (C-1/C-4), 62.34 (NCH2Ph), 72.05 (OCH2Ph), 81.58
(C-2), 87.90 (C-3), 127.50, 127.80, 127.92, 128.43, 128.45,
128.81, 137.00, 137.11 (Ar-C), 175.92 (C-6). Anal. Calcd
for C20H21NO3: C, 74.28; H, 6.55. Found C, 74.30;
3. (a) Compernolle, F.; Joly, G.; Peeters, K.; Toppet, S.;
Hoornaert, G.; Kilonda, A.; Bila, B. Tetrahedron 1997, 53,
12739; (b) Kilonda, A.; Compernolle, F.; Toppet, S.;
Hoornaert, G. J. Tetrahedron Lett. 1994, 35, 9047.
4. (a) Dhavale, D. D.; Desai, V. N.; Sindkhedkar, M. D.;
Mali, R. S.; Castellari, C.; Trombini, C. Tetrahedron:
Asymmetry 1997, 9, 1475; (b) Dhavale, D. D.; Saha, N. N.;
Desai, V. N. J. Org. Chem. 1997, 62, 7482; (c) Dhavale, D.
D.; Desai, V. N.; Saha, N. N. Chem. Commun. 1999, 1719;
(d) Patil, N. T.; Tilekar, J. N.; Dhavale, D. D. J. Org.
Chem. 2001, 66, 1065; (e) Saha, N. N.; Desai, V. N.;
Dhavale, D. D. Tetrahedron 2001, 57, 39; (f) Patil, N. T.;
Tilekar, J. N.; Dhavale, D. D. Tetrahedron Lett. 2001, 42,
747; (g) Dhavale, D. D.; Chaudhari, V. D.; Tilekar, J. N.
Tetrahedron Lett. 2003, 44, 7321; (h) Dhavale, D. D.;
25
H, 6.52. Data for 5b: ½aꢁD ꢀ 11:42 (c 0.175, CHCl3). IR
(neat): 2733, 1724cmꢀ1 1H NMR (300MHz, CDCl3):
;
d 1.28 (t, J = 7.3Hz, 3H, CH3), 2.55–2.75 (m, 3H, H-1a,
H-5a, H-5b), 2.89–3.00 (m, 2H, H-1b, H-4), 3.31 (d,
J = 13.1Hz, 1H, NCH2Ph), 3.61 (s, exchangeable with
D2O, 1H, OH), 3.86 (dd, J = 0.8, 5.8Hz, 1H, H-3), 3.97 (d,