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M. M. Cruz Silva et al. / Tetrahedron: Asymmetry 15(2004) 1173–1179
4.4.2. 5b,6b-Epoxy-20-oxo-pregnan-3b-yl acetate, 20b. To
a solution of 5,6-epoxy-20-oxo-pregnan-3b-yl acetate 5,
(180 mg, a=b ratio 1.3:8.7) in toluene (8 ml) and octanol
(2 ml), lipase AY (200 mg) was added and the reaction
shaken at45 °C. After 3 days, the enzyme was filtered off
and the solvent was evaporated. 5b,6b-Epoxy-20-oxo-
pregnan-3b-yl acetate 20b (126 mg, 70% yield) was isol-
References and notes
1. (a) Guardiola, F.; Codony, R.; Addis, P. B.; Rafecas, M.;
Boatella, J. Fd. Chem. Toxic. 1996, 34, 193–211; (b) Smith,
L. L. Lipids 1996, 31, 453–487.
2. Hwang, P. L. BioEssays 1991, 13, 583–589.
3. (a) OÕCallaghan, Y. C.; Woods, J. A.; OÕBrien, N. M. Cell
Biol. Toxicol. 2001, 17, 127–137; (b) OÕSullivan, A. J.;
OÕCallaghan, Y. C.; Woods, J. A.; OÕBrien, N. M. J. Appl.
Toxicol. 2003, 23, 191–197.
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Sevanian, A.; Peterson, A. R. Proc. Natl. Acad. Sci.
1984, 81, 4198–4202; (c) Raaphorst, G. P.; Azzam, E. I.;
Langlois, R.; van Lier, J. E. Biochem. Pharmacol. 1987, 36,
2369–2372.
5. (a) Kupchan, S. M.; Anderson, W. K.; Bollinger, P.;
Doskotch, R. W.; Smith, R. M.; Renauld, J. A. S.;
Schnoes, H. K.; Burlingame, A. L.; Smith, D. H. J. Org.
Chem. 1969, 34, 3858–3866; (b) Habtemariam, S. Planta
Medica 1997, 63, 15–17; (c) Habtemariam, S.; Skelton, B.
W.; Waterman, P. G.; White, A. H. J. Natl. Prod. 2000,
63, 512–513; (d) Jayaprakasam, B.; Zhang, Y.; Seeram, N.
P.; Nair, M. G. Life Sciences 2003, 74, 125–132.
6. Smith, J. G. Synthesis 1984, 8, 629–656.
ated by flash chromatography (petroleum ether/ethyl
21
D
acetate 2:1) as a single diastereomer. ½a ¼ þ50:6, (c
1.18, CHCl3) {lit.8a ½a ¼ þ50}, mp 132–134 °C (lit.8a
D
1
132–136 °C), as indicated by H NMR.
4.4.3. 5b,6b-Epoxy-17-oxo-androstan-3b-yl acetate, 30b.
To a solution of 5,6-epoxy-17-oxo-androstan-3b-yl
acetate 6 (180 mg, a=b ratio 1:9) in toluene (8 ml) and
octanol (2 ml), lipase AY (200 mg) was added and the
reaction shaken at 45 °C. After 3 days, the enzyme was
filtered off and the solvent evaporated. 5b,6b-Epoxy-17-
oxo-androstan-3b-yl acetate 30b (135 mg, 75% yield) was
isolated by flash chromatography (petroleum ether/ethyl
21
D
acetate 1:1) as a single diastereomer, ½a ¼ þ43:0, (c
1.4, CHCl3) {lit.29 ½a ¼ þ40:5}, mp 186.7–188 °C (lit.29
D
7. Kirk, D. N.; Hartshorn, M. P. In Steroid Reaction
Mechanism; Eabrorn, C., Chapman, N. B., Eds.; Elsevier:
London, 1968; p 69.
1
185–187 °C), as indicated by H NMR.
8. (a) Akhtar, M.; Barton, D. H. R. J. Am. Chem. Soc. 1964,
86, 1528–1536; (b) Matthews, G. J.; Hassner, A. In
Organic Reactions in Steroid Chemistry; Fried, J., Ed-
wards, J. A., Eds.; Van Nostrand Reinhold Company:
New York, 1972; 2, p 1.
9. (a) Shiota, M.; Ogihara, T.; Watanabe, Y. Bull. Chem.
Soc. Jpn. 1961, 34, 40–42; (b) Hanson, J. R.; Truneh, A. J.
Chem. Soc., Perkin Trans. 1 1988, 2001–2003.
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1990, 366–367; (b) Galagovsky, L. R.; Gros, E. G. J.
Chem. Res. (S) 1993, 137.
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ran, S. J. Org. Chem. 1992, 57, 1928–1930; (b) Salvador, J.
4.5. Total hydrolysis of 3b-acetoxy-5a,6a- and 5b,6b-
epoxysteroids
In a typical experiment, the 3b-acetoxy-5,6-epoxysteroid
(150 mg), obtained by permanganate epoxidation, was
dissolved in diisopropyl ether (35 ml) presaturated with
water and then C. rugosa lipase (1.8 g) added. The
mixture was shaken at 250 rpm, 45 °C and after 3 days
the reactions were shown to have gone to completion.
The products were isolated and the a=b ratios quantified
1
by H NMR: 5,6-epoxycholestan-3b-ol 7 (136 mg, a=b
ꢀ
A. R.; Sa e Melo, M. L.; Campos Neves, A. S. Tetrahedron
ratio 1:9), 5,6-epoxy-3b-hydroxypregnan-20-one
(130 mg, a=b ratio 1.2:8.8) and 5,6-epoxy-3b-hydroxy-
androstan-17-one 9 (135 mg, a=b ratio 0.9:9.1).
8
Lett. 1996, 37, 687–690; (c) Singh, N.; Lee, D. G. Org.
Proc. Res. Dev. 2001, 5, 599–603.
12. Yang, D.; Jiao, G.-S. Chem. Eur. J. 2000, 6, 3517–3521.
13. (a) Marchon, J.-C.; Ramasseul, R. Synthesis 1989, 5, 389–
4.6. 5b,6b-Epoxycholestan-3b-ol 1b
ꢁ
391; (b) Tavares, M.; Ramasseul, R.; Marchon, J.-C.;
Bachet, B.; Brassy, C.; Mornon, J.-P. J. Chem. Soc.,
Perkin Trans. 2 1992, 1321–1329; (c) Kesavan, V.;
Chandrasekaran, S. J. Org. Chem. 1998, 63, 6999–7001;
(d) Zhang, J.-L.; Zhou, H.-B.; Huang, J.-S.; Che, C.-M.
Chem. Eur. J. 2002, 8, 1554–1562.
To a solution of 5,6-epoxycholestan-3b-ol 7 (136 mg, a=b
ratio 1:9) in toluene (6 ml) and vinyl acetate (1 ml), Lipase
AY (100 mg) was added and the reaction shaken at 45 °C.
After 3 days the enzyme was filtered off and the solvent
evaporated. 5b,6b-Epoxycholestan-3b-ol 1b (100.5 mg,
74% yield) was isolated by flash chromatography
14. (a) Mousseron-Canet, M.; Labeeuw, B.; Lanet, J.-C. Bull.
Soc. Chim. France 1968, 5, 2125–2130; (b) Hanson, J. R.;
Terry, N.; Uyanik, C. J. Chem. Res. (S) 1998, 50–51; (c)
Hanson, J. R.; Hitchcock, P. B.; Kiran, I. J. Chem. Res.
(S) 1999, 538–539.
15. (a) Carrea, G.; Riva, S. Angew. Chem., Int. Ed. 2000, 39,
2226–2254; (b) Koeller, K. M.; Wong, C.-H. Nature 2001,
409, 232–240; (c) Riva, S. Curr. Opin. Chem. Biol. 2001, 5,
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16. (a) Njar, V. C. O.; Caspi, E. Tetrahedron Lett. 1987, 28,
6549–6552; (b) Adamczyk, M.; Chen, Y.-Y.; Fishpaugh,
J. R.; Gebler, J. C. Tetrahedron: Asymmetry 1993, 4, 1467–
1468; (c) Baldessari, A.; Maier, M. S.; Gros, E. G.
Tetrahedron Lett. 1995, 36, 4349–4352; (d) Danieli, B.;
Lesma, G.; Luisetti, M.; Riva, S. Tetrahedron 1997, 53,
5855–5862; (e) Secundo, F.; Carrea, G.; De Amici, M.;
(petroleum ether/ethyl acetate 1:1) as a single diastereo-
21
D
mer, ½a ¼ þ8:0, (c 0.5, CHCl3) {lit.29 ½a ¼ þ7:8}, mp
D
127–129 °C (lit.29 128–131 °C), as indicated by 1H NMR.
Acknowledgements
~
^
Thanks are due to Fundaßcao para a Ciencia e Tecno-
logia (FCT) partly through POCTI (FEDER) and to the
CNR-GRICES bilateral exchange program (2003–2004)
for financial support. M. M. Cruz Silva wishes to thank
~
Fundaßcao Calouste Gulbenkian for a Ph.D. grant.