ˆ
R. Chenevert, F. Jacques / Tetrahedron: Asymmetry 17 (2006) 1017–1021
1020
was added and the pH maintained at its initial value by
addition of 0.25 M aqueous NaOH. After 2 h, the solution
became clear and the aqueous mixture was filtered using
0.22 lm membrane filter, and the retained enzyme was
washed with H2O. The aqueous solution was extracted
with CH2Cl2 (10 · 20 mL), and the organic layer was dried
over MgSO4 and concentrated. Flash chromatography of
189.1239. Found: 189.1237. The same protocol was applied
to the reduction of (+)-9 (16 mg, 0.067 mmol; from CRL
acylation) to yield (ꢀ)-10 (12 mg, 96%) as a colorless
22
oil: ½aꢁD ¼ ꢀ10:8 (c 0.6, CH3OH); spectral data as above.
Acknowledgements
the residue with Et2O gave monoacetate (ꢀ)-8 (202 mg,
22
92%, ee = 90%) as a colorless oil. ½aꢁD ¼ ꢀ61:9 (c 1.44,
The authors would like to thank the Natural Sciences and
Engineering Research Council of Canada (NSERC), for
financial support. We also thank Dr. Vourloumis from
Anadys Pharmaceuticals, for providing the specific rotation
of compound (+)-9.
CHCl3), spectral data as above.
3.8. (1R,2R,4S,5S)-2,4-Diazido-5-hydroxycyclohexyl
acetate 9
3.8.1. Enzymatic acylation of diol 5. To a solution of diol
5 (250 mg, 1.26 mmol) in vinyl acetate (5 mL) was added
C. rugosa lipase (100 mg) and the mixture stirred at rt for
2 days. The enzyme was filtered, washed with CH2Cl2
and the solvent evaporated. Flash chromatography of the
crude product with hexanes/EtOAc (3:1) provided mono-
References
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3. Magnet, S.; Blanchard, J. S. Chem. Rev. 2005, 105, 477–
497.
acetate (+)-9 (258 mg, 85%, ee P99%) as a colorless oil.
22
½aꢁD ¼ þ22 (c 0.6, CHCl3); IR (NaCl) 3440, 2919, 2101,
1732, 1374, 1235, 1031 cmꢀ1; 1H NMR (400 MHz, CDCl3):
d 1.22 (s, 1H), 1.36 (m, 1H), 1.46 (m, 1H), 2.08 (s, 3H), 2.25
(m, 1H), 2.36 (m, 1H), 3.30 (m, 2H), 3.52 (m, 1H), 4.70 (m,
1H); 13C NMR (100 MHz, CDCl3): d 21.2, 32.2, 36.1, 60.7,
63.9, 70.9, 72.7, 170.2; HRMS (CI, NH3) calcd for
C8H13N6O3 (M+H)+: 241.1049. Found: 241.1044.
4. Bastida, A.; Hidalgo, A.; Chiara, J. L.; Torrado, M.;
Corzana, F.; Perez-Canadillas, J. M.; Groves, P.; Garcia-
˜
Junceda, E.; Gonzalez, C.; Jimenez-Barbero, J.; Asensio, J. L.
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3.8.2. Enzymatic hydrolysis of diacetate 7. Diacetate 7
(524 mg, 1.86 mmol) was suspended in a mixture of buf-
fered aqueous solution (10 mL, 0.1 M sodium phosphate,
pH 6.2) and toluene (10 mL) at room temperature. CAL-
B (500 mg) was added and the pH was maintained at its ini-
tial value by addition of 0.25 M aqueous NaOH. The reac-
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diacetate had disappeared (ꢂ3 days). The mixture was
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separated and aqueous phase extracted with CH2Cl2
(3 · 20 mL). The combined organic layers were dried over
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the residue with hexanes/EtOAc (3:1) gave monoacetate
(+)-9 (144 mg, 32%, ee P99%) as
a colorless oil.
½aꢁD ¼ þ21:6 (c 1.0, CHCl3), spectral data as above.
22
3.9. Determination of absolute configurations by chemical
correlation and preparation of both enantiomers of
dideoxystreptamine monoacetate 10
A solution of (ꢀ)-8 (21 mg, 0.11 mmol; from PLE hydro-
lysis) in methanol (10 mL) was stirred at rt with 10%
Pd-on-carbon (50 mg) under hydrogen (55 psi) for 5 h.
The catalyst was then removed by filtration, washed with
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methanol, and the solvent evaporated to give (+)-10
22
(20 mg, 93%) as a colorless oil: ½aꢁD ¼ þ9:7 (c 1.0,
´
20. Verhelst, S. H. L.; Magnee, L.; Wennekes, T.; Wiedenhof,
CH3OH); IR (NaCl) 3441, 2525, 1721, 1444, 1260 cmꢀ1
;
W.; van der Marel, G. A.; Overkleeft, H. S.; van Boeckel, C.
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1H NMR (400 MHz, CD3OD): d 1.25 (s, 1H), 1.35 (m,
1H), 1.93 (s, 3H), 2.10 (m, 1H), 2.55 (m, 1H), 3.20 (m,
2H), 3.40 (m, 1H), 3.60 (m, 1H); 13C NMR (100 MHz,
CD3OD): d 22.0, 29.9, 41.6, 54.6, 55.9, 71.4, 73.2, 171.3;
HRMS (CI, NH3) calcd for C8H17O3N2 (M+H)+: