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mixture was stirred at room temperature for 2 h, diluted with Et2O
(11 mL) and saturated solutions of NaS2O3(aq) (4 mL) and NaH-
CO3(aq) (8 mL) were added. The mixture was extracted with CH2Cl2
(3ꢂ20 mL) and the combined organic layers dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by
flash chromatography eluting with hexanes/EtOAc (1:4) to give the
title compound (0.31 g, 99%) as a colourless oil. Rf (80% EtOAc/hex-
20
ane) 0.31; [
a
]
ꢁ42.3 (c 0.9, CHCl3); nmax (film) 2932, 1733, 1679,
D
1613, 1475 cmꢁ1 dH (400 MHz; CDCl3) 8.28–8.26 (1H, m, H-500), 7.94
;
(1H, s, H-200), 7.79–7.73 (2H, m, H-700, H-800), 7.51 (1H, ddd, J 8.2, 6.2,
2.1, H-600), 7.36–7.25 (5H, m, Ar–H), 5.00–4.95 (3H, m, H-2, H-30),
4.68 (1H, d, J 11.9, OCHa,HbPh), 4.53 (1H, d, J 11.9, OCHa,HbPh), 3.98
(1H, br s, CHa,Hb-6), 3.49 (1H, br s, H-3), 2.93–2.82 (2H, m, CHa,Hb-
10, CHa,Hb-6), 2.72 (1H, dd, J 14.3, 5.8, CHa,Hb-10), 1.97–1.87 (2H, m,
CHa,Hb-4, CHa,Hb-5), 1.69–1.60 (1H, m, CHa,Hb-4), 1.45 (9H, s, tBuO),
1.41–1.40 (1H, m, CHa,Hb-5); dC (100 MHz; CDCl3) 200.0, 160.9,
155.7, 148.3, 146.5, 138.3, 134.4, 128.3, 127.6 (2C), 127.5, 127.2, 126.7,
121.8, 80.2, 73.9, 70.3, 53.8, 50.0, 40.9, 39.2, 28.4, 24.4, 19.4; m/z (EI)
491 (1, Mþ) 390 (13), 283, (21), 202 (27), 187 (23), 160 (52), 137 (15),
130 (20), 98 (14), 91 (100), 77 (11), 71 (14%). HRMS (EI): Mþ, found
491.2420. C28H33N3O5 requires 491.2420.
4.9.5. (2R,3S)-3-Hydroxy-2-[20-oxo-30-(400-oxo-4H-quinazolin-300-
yl)propyl]piperidine ((þ)-febrifugine) (1)
A solution of N-, O-protected febrifugine 32 (0.28 g, 0.57 mmol)
in 6 M HCl(aq) (35 mL) was stirred under reflux for 40 min. The
mixture was cooled to room temperature and basified to pH 9 by
careful addition of saturated K2CO3(aq). The reaction mixture was
extracted with CHCl3 (3ꢂ20 mL) and the combined organic layers
dried over anhydrous K2CO3, concentrated under reduced pressure
and purified by reverse phase (C18) flash chromatography eluting
with H2O/CH3CN (10:1) to give the title compound (0.12 g, 67%) as
8. (a) Herczegh, P.; Kovacs, I.; Szilagyi, L.; Varga, T.; Dinya, Z.; Sztaricskai, F. Tet-
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a white solid. Recrystallisation of this material using EtOAc gave
20
10. Ashoorzadeh, A.; Caprio, V. Synlett 2005, 346–348.
colourless crystals. Mp 139–141 ꢀC; Rf (20% MeOH/CHCl3) 0.31; [
a]
D
11. Keck, G. E.; Andrus, M. B.; Romer, D. R. J. Org. Chem. 1991, 56, 417–420.
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þ26.4 (c 0.1, EtOH); nmax (solid) 3285, 3149, 2930, 2854, 1723, 1673,
1611, 1473 cmꢁ1 dH (300 MHz; CDCl3) 8.20 (1H, dd, J 8.2, 1.1, H-500),
;
13. Gmiener, P.; Dagmar, J. J. Org. Chem. 1995, 60, 3910–3915.
7.90 (1H, s, H-200), 7.78 (1H, ddd, J 8.4, 7.0,1.5, H-700), 7.73 (1H, dd, J 8.4,
1.3, H-800), 7.51 (1H, ddd, J 8.2, 6.7,1.7, H-600), 4.89(1H, d, J 17.4, CHa,Hb-
30), 4.82 (1H, d, J 17.4, CHa,Hb-30), 3.28 (1H, ddd, J 10.4, 9.1, 4.4, H-3),
3.11 (1H, dd, J 15.9, 4.7, CHa,Hb-10), 3.00–2.93 (1H, m, CHa,Hb-6), 2.87
(1H, ddd, J 8.9, 7.4, 4.7, H-2), 2.63 (1H, dd, J 15.9, 7.4, CHa,Hb-10), 2.58
(1H, td, J 12.1, 2.9, CHa,Hb-6), 2.12–2.05 (1H, m, CHa,Hb-4), 1.75–1.71
(1H, m, CHa,Hb-5), 1.57–1.48 (1H, m, CHa,Hb-5), 1.37–1.31 (1H, m,
CHa,Hb-4); dC (75 MHz; CDCl3) 202.6,161.0,148.2,146.4,134.5,127.6,
127.4, 126.8, 121.9, 72.3, 60.2, 54.8, 46.0, 44.1, 34.5, 25.6. HRMS
(FABþ): MHþ, found 302.1510. C16H20N3O3 requires 302.1505.
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Acknowledgements
22. Murata, K.; Takano, F.; Fushiya, S.; Oshima, Y. Biochem. Pharmacol. 1999, 58,
1593–1601.
We thank The University of Auckland Staff Research Committee
and Doctoral Scholarship Scheme for funding of this work.
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