1934
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2. Ceruti, M.; Rocco, F.; Viola, F.; Balliano, G.; Milla, P.;
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47. General procedure for regioselective mono- and diepoxida-
tion with UHP/MTO. Farnesylcoumarin (1 mmol) was
added to a magnetically stirred suspension of methyl-
2
2
4. Jolidon, S.; Polak-Wyss, A.; Hartman, P. G.; Guerry, P.
G. In Recent Advances in the Chemistry of Anti-infective
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2
2
2
2
trioxorenium (0.2 mmol) and urea–H
in CHCl (8 mL/mmol) previously cooled to 0 C. After
2
O
2
adduct (2 mmol)
ꢁ
3
ꢁ
38, 373.
stirring for about 90 min at 5 C to complete dis-
appearance of the starting material (TLC), the mixture
6. Dehmlow, H.; Aebi, J. D.; Jolidon, S.; Ji, Y. H.; von der
Mark, E. M.; Himber, J.; Morand, O. H. J. Med. Chem.
was diluted with CHCl
(Na SO ) giving in all cases the terminal monoepoxide
3
, washed with brine, and dried
2003, 46, 3354.
2
4
7. Buckner, F. S.; Griffin, J. H.; Wilson, A. J.; Van
Voorhis, W. C. Antimicrob. Agents Chemother. 2001, 45,
(yields 60–65%). Using more methyltrioxorenium (0.3
O
mmol) and urea–H
2
2
adduct (2.5 mmol), after 3h stir-
ꢁ
0
0
0
0
1210.
ring at 20 C we obtained the corresponding 6 ,7 :10 ,11 -
diepoxide as major product. Mono- and diepoxide were
easily separed by column chromatography (hexane/
EtOAc 9:1 v/v).
8. Oliaro Bosso, S.; Ceruti, M.; Balliano, G.; Matsuda, S. P. T.;
Milla, P.; Rocco, F.; Viola, F. 93rd AOCS Annual Meet-
ing & Expo., Montreal, Quebec, Canada, May 5–8, 2002.
9. Wendt, K. U.; Poralla, K.; Schulz, G. E. Science 1997,
2
3
3
3
All mono- and diepoxides have been spectroscopically
characterized and analytical data have been obtained. For
example, (E)-7-(5-{3-[2-(3,3-dimethyloxiranyl)-ethyl]-3-
methyloxiranyl}-3-methylpent-2-enyloxy)-chromen-2-one
2
77, 1811.
0. Wendt, K. U.; Lenhart, A.; Schulz, G. E. J. Mol. Biol.
999, 286, 175.
1
1. Wendt, K. U.; Schulz, G. E.; Corey, E. J.; Liu, D. R.
Angew. Chem., Int. Ed. 2000, 39, 2812.
(12) was isolated as a colorless oil (56%, yield); IR (liquid
ꢀ
1 1
film) 1732, 1614, 1555, 1506, 1436, 1235, 1120 cm ; H
2. Lenhart, A.; Reinert, D. J.; Aebi, J. D.; Dehmlow, H.;
Morand, O. H.; Schulz, G. E. J. Med. Chem. 2003, 46,
NMR (400 MHz, CDCl ) d: 7.61 (1H, d, J=9.5 Hz, H-4),
3
7.33 (1H, d, J=8.5 Hz, H-5), 6.84–6.79 (2H, m, H-6 and
H-8), 6.22 (1H, d, J=9.5 Hz, H-3), 5.48 (1H, tq, J=6.8
2063.
0
3
3
3
3. Viola, F.; Ceruti, M.; Cattel, L.; Milla, P.; Poralla, K.;
Balliano, G. Lipids 2000, 35, 297.
4. Ceruti, M.; Balliano, G.; Rocco, F.; Milla, P.; Arpicco, S.;
Cattel, L.; Viola, F. Lipids 2001, 36, 629.
5. El-Razek, M. H. A.; Ohta, S.; Ahmed, A. A.; Hirata, T.
Phytochemistry 2001, 58, 1289 and references therein.
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G. M. Gazz. Chim. Ital. 1989, 119, 385.
Hz, J=1.0 Hz, H-2 ), 4.58 (2H, d, J=6.3Hz, OCH
0
2
),
),
0
0
2.38–2.24 (2H, m, H-6 and H-10 ), 2.12 (2H, m, 4 -CH
0
2
0
0
1.77–1.47 (6H, m, 5 -CH , 8 -CH , and 9 -CH ), 1.75 (3H,
2
2
2
0
0
d, J=1.0 Hz, 3 -CH ), 1.24 (3H, s, 11 -CH ), 1.16 (3H, s,
3
3
0
0
11 -CH
+
3
), 1.10 (3H, s, 7 -CH
(MH , 20), 381 (58), 162 (100). Anal. calcd for C24
C, 72.34; H, 7.59. Found: C, 72.40; H, 7.38.
3
); MS (CIMS) m/z (%) 399
30 5
H O :
3
3
48. IC50 values (inhibitor concentrations that reduce by
50% the enzymatic conversion of squalene to hopene)
3
3
3
3
4
4
4
4
4
8. Kunz, K.; Weidle, H.; Fischer, K. J. Prakt. Chem. 1934,
were determined at 10 mM substrate concentration.
[ C]squalene was obtained by incubating 1 microCi of
14
141, 350.
1
4
9. Cravotto, G.; Chimichi, S.; Robaldo, B.; Boccalini, M.
Tetrahedron Lett. 2003, 44, 8383.
0. Sato, T.; Hoshino, T. Biosci. Biotechnol. Biochem. 1999,
[ C]mevalonolactone with S10 supernatant of pig liver
homogenate (25 mg of proteins) following the method of
4
9
Popjak, in the presence of the oxidosqualene cyclase
´
6
3, 1171.
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1, 197.
2. van Tamelen, E. E.; Curphey, T. J. Tetrahedron Lett.
962, 121.
3. Onoda, T.; Shirai, R.; Koiso, Y.; Iwasaki, S. Tetrahedron
996, 52, 14543.
4. Al-Ajlouni, A.; Espenson, J. H. J. Am. Chem. Soc. 1995,
17, 9243.
inhibitor U-18666A. Under these conditions the bulk of
radioactivity of nonsaponifiable extract was shared
between squalene and oxidosqualene, which can be easily
1
5
0
separated by TLC.
49. Popjak, G. In Methods in Enzymology, Steroids and
1
´
Terpenoids. Clayton, R. B., Ed.; Academic Press: New
York, 1969; Vol. XV, pp 438–443.
50. Balliano, G.; Viola, F.; Ceruti, M.; Cattel, L. Biochim.
Biophys. Acta 1988, 959, 9.
1
1