N. Al-Maharik, N. P. Botting / Tetrahedron Letters 47 (2006) 8703–8706
8705
HO
O
O
O
O
3, BF3.Et2O
PhSH, Im
NMP, rt
4
CH2Cl2, 4Å MS, rt
O
O
O
O
(78%)
(88%)
O
O
4
4
O
O
O
O
4
4
8
9
MeO
AcO
O
HO
O
AcO
O
K2CO3, THF
MeOH, 40 oC
HO
HO
AcO
O
O
O
O
O
O
HO
(92%)
O
OH
O
O
4
OH
O
10
7c
O
4
Scheme 3.
daidzein25 7a, glycitein 7b and genistein 7c in 90–92%
yields, was affected under the action of K2CO3 in
MeOH:THF:H2O (5:5:0.5).
8. Sacks, F. M.; Lichtenstein, A.; Van Horn, L.; Harris, W.;
Kris-Etherton, P.; Winston, M. Circulation 2006, 113,
1034.
9. Henderich, S. J. Chromatogr. B 2002, 777, 203.
10. de Pascual-Teresa, S.; Hallund, J.; Talbot, D.; Schroot, J.;
Williams, C. M.; Bugel, S.; Cassidy, A. J. Nutr. Biochem.
2006, 17, 257.
11. Wang, H.-J.; Murphy, P. A. J. Agric. Food Chem. 1996,
44, 2377.
12. Setchell, K. D. J. Nutr. 2000, 130, 654S.
In conclusion, we have developed an efficient, high yield-
ing synthesis of isoflavone 7-glucuronides using a novel
N-(4-methoxyphenyl)-trifluoroacetimidate glucuronsyl
donor. The 4-hexanoyl derivatives of daidzein and glyci-
tein were used in the coupling reaction, both for protec-
tion and to improve solubility, while for genistein the
hydroxyl group at the 5-position also had to be pro-
tected. These compounds are now being used to investi-
gate the biological activity and pharmacokinetics of
these important human metabolites of dietary
isoflavones.
´
13. Bennetau-Pelissero, C.; Latonnelle, K.; Sequeira, A.;
Lamothe, V. Analusis 2000, 28, 763.
14. Ren, M. Q.; Kuhn, G.; Wegner, J.; Chen, J. Eur. J. Nutr.
2001, 40, 135.
15. Heinonen, S. M.; Wahala, K.; Liukkonen, K. H.; Aura, A.
M.; Poutanen, K.; Adlercreutz, H. J. Agric. Food Chem.
2004, 52, 2640.
16. King, R. A.; Bursill, D. B. Am. J. Clin. Nutr. 1998, 67, 867.
17. Setchell, K. D.; Faughnan, M. S.; Avades, T.; Zimmer-
Nechemias, L.; Brown, N. M.; Wolfe, B. D.; Brashear, W.
T.; Desai, P.; Oldfield, M. F.; Botting, N. P.; Cassidy, A.
Am. J. Clin. Nutr. 2003, 77, 411.
Acknowledgement
This work was funded by the Food Standards Agency
(FSA) under Contract T05028.
18. Fairley, B.; Botting, N. P.; Cassidy, A. Tetrahedron 2003,
59, 5407.
19. Lewis, P.; Kaltia, S.; Wahala, K. J. Chem. Soc., Perkin
Trans. 1 1998, 2481.
´
20. Zemplen, G.; Farkas, L. Chem. Ber. 1943, 76, 1110.
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References and notes
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P. A. J. Nutr. 1994, 124, 1789S.
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J. E. Lancet 1997, 350, 23.
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2001, 90, 157.
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L. Annu. Rev. Nutr. 2001, 21, 381.
7. Cassidy, A.; Albertazzi, P.; Nielsen, I. L.; Hall, W.;
Williamson, G.; Tetens, I.; Atkins, S.; Cross, H.; Manios,
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2006, 65, 76.
22. Li, M.; Han, X.; Yu, B. J. Org. Chem. 2003, 68, 6842.
23. All new compounds gave satisfactory spectroscopic and
microanalytical data.
24. Methyl (40-O-hexanoyldaidzein-7-yl-b-D-200-300,400-tri-O-
acetylglucopyranosid)urinate 6a: A suspension of 40-O-
hexanoyldaidzein 5a (0.1 g, 0.28 mmol), glucuronyl triflu-
˚
oroacetamidate 3 (0.30 g, 0.57 mmol) and 4 A molecular
sieves (0.3 g) in dry CH2Cl2 (5 mL) was stirred under N2 at
rt. BF3ÆEt2O (10 lL, 85 lmol) was added, once the colour
of the suspension had turned to orange. After 6 h of
stirring at rt, the reaction mixture was quenched with a
drop of Et3N. After filtration, the solvent was evaporated
under reduced pressure, and the orange oily residue was
subjected to silica gel chromatography (ethyl acetate/
petroleum ether 1:1) furnishing 6a as a white crystalline
20
solid (0.149 g, 81%), mp 193–194 ꢁC; ½aꢁD ꢀ24.2