898
S. Kim et al. / Bioorg. Med. Chem. Lett. 12 (2002) 895–898
3. Staib, P.; Kretschmar, M.; Nichterlein, T.; Hof, H.;
Morschhauser, J. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6102.
4. Brown, D. H., Jr.; Giusani, A. D.; Chen, X.; Kumamoto,
C. A. Mol. Microbiol. 1999, 34, 651 and references therein.
5. (a) Liu, H.; Styles, C. A.; Fink, G. R. Science 1993, 262,
1741. (b) Liu, H.; Kahler, J.; Fink, G. R. Science 1994, 266,
1723. (c) Kahler, J.; Fink, G. R. Proc. Natl. Acad. Sci. U.S.A.
1996, 93, 13223.
6. Mitchell, A. P. Curr. Opin. Microbiol. 1998, 1, 687.
7. Stoldt, V. R.; Sonnenborn, A.; Leuker, C. E.; Ernst, J. F.
EMBO J. 1997, 16, 1982.
8. Lo, H. J.; Kahler, J. R.; DiDomenico, B.; Loebenberg, D.;
Cacciapuoti, A.; Fink, G. R. Cell 1997, 90, 939 and references
therein.
9. Brown, B. R.; Johnson, A. D. Science 1997, 277, 105.
10. Oh, K.-B.; Miyazawa, H.; Naito, T.; Matsuoka, H. Proc.
Natl. Acad. Sci. U.S.A. 2001, 98, 4664.
11. For an alternative preparation, see: Kulkarni, Y. S.; Niwa,
M.; Ron, E.; Snider, B. B. J. Org. Chem. 1987, 52, 1568.
12. For the precedent E/Z isomerization problems, see: Patel,
D. V.; Schmidt, R. J.; Biller, S. A.; Gordon, E. M.; Robinson,
S. S.; Manne, V. J. Med. Chem. 1995, 38, 2906.
13. (a) For the yeast cell growth inhibition assay, C. albicans
ATCC 10231 cells were grown at 30 ꢀC in YPD medium (10g
of yeast extract, 20g of polypeptone, and 20g of glucose per
liter) with vigorous shaking. After 48 h of incubation, cells
were harvested and washed twice with sterile distilled water,
and inoculated into fresh YPD medium to give an initial cell
density of approximately 107 cells/mL. Stock solutions of test
compounds were prepared in 100% dimethyl sulfoxide
(DMSO) and stored at À20 ꢀC. Each stock solution was dilu-
ted with YPD medium to prepare serial 2-fold dilutions in the
range of 100–0.1 mg/mL before use. The final concentration of
DMSO was less than 0.5%. Cells were then grown with or
without a prescribed concentration of test compound with
vigorous shaking. After 4 h of incubation at 30 ꢀC, the cell
density at A610 was measured. A cell suspension of 107 cells/
mL gave an A610 value of approximately 1.0. (b) For the yeast-
to-hypha transition assay, stock solutions of test compounds
were prepared and diluted with a glucose salts (GS) medium as
described above. GS medium containing a prescribed con-
centration of the test compound was added to 105 cells/mL of
washed yeast cells in Petri dishes (diameter, 30mm), mixed,
and incubated for 4 h at 37 ꢀC. The percentages of yeast and
hypha were determined microscopically by counting 200 cells
from triplicate dishes. Inhibitory activity was defined to be the
concentration (mg/mL) giving 50% inhibition (IC50) relative to
the control (GS medium containing 0.5% DMSO).
14. A representative example: compound 1: 1H NMR (CDCl3,
300 MHz) d 5.63 (d, J=1.2 Hz, 1H), 5.01 (m, 2H), 2.10–2.13
(m, 7H), 1.89–2.03 (m, 5H), 1.61 (d, J=1.2 Hz, 3H), 1.53 (s,
6H); 13C NMR (CDCl3, 75 MHz) d 170.81, 161.99, 135.31,
130.43, 123.18, 121.70, 114.09, 40.20, 38.64, 25.65, 24.92,
1
24.65, 18.14, 16.66, 15.01. 3e: H NMR (CDCl3, 300 MHz) d
5.61 (d, J=1.5 Hz, 1H), 5.30(m, 1H), 4.98–5.03 (m, 2H), 4.52
(d, J=7.2 Hz, 2H), 2.08–2.10 (m, 7H), 1.88–2.02 (m, 5H), 1.65
(td, J=12.8, 1.0Hz, 8H), 1.53 (s, 6H); 13C NMR (CDCl3,
75 MHz) d 165.85, 158.88, 137.57, 135.10, 130.38, 123.21,
121.90, 118.01, 114.53, 59.46, 39.95, 38.65, 25.66, 24.95, 24.76,
24.65, 17.82, 16.99, 16.66, 14.99. 3g: 1H NMR (CDCl3, 30 0
Hz) d 5.61 (d, J=1.2 Hz, 1H), 5.30(td, J=7.2, 1.3 Hz, 1H),
4.99–5.03 (m, 4H), 4.54 (d, J=7.2 Hz, 2H), 2.08–2.10 (m, 7H),
1.88–2.03 (m, 12H), 1.64 (d, J=0.9 Hz, 3H), 1.61 (d, J=0.9
Hz, 6H), 1.53 (s, 12H); 13C NMR (CDCl3, 75 MHz) d 166.86,
159.83, 141.78, 136.10, 135.39, 131.38, 131.28, 124.33, 124.21,
123.69, 122.90, 118.72, 115.56, 83.18, 60.48, 40.95, 39.68,
39.65, 39.55, 26.72, 26.66, 26.22, 25.97, 25.67 (2C), 18.82,
1
17.67, 16.91, 16.47, 16.00. 5d: H NMR (CDCl3, 300 MHz) d
5.79 (dddd, J=15.9, 10.8, 5.7, 5.7 Hz, 1H), 5.50 (s, 1H), 5.41
(bs, 1H), 4.99–5.16 (m, 4H), 3.84–3.91 (m, 2H), 2.06–2.09 (m,
7H), 1.88–2.02 (m, 4H), 1.61 (d, J=0.9 Hz, 3H), 1.53 (s, 6H);
13C NMR (CDCl3, 75 MHz) d 166.05, 153.37, 134.90, 133.55,
130.33, 123.23, 122.13, 116.90, 115.09, 65.47, 39.79, 38.67,
1
25.70, 25.08, 24.67, 17.35, 16.67, 15.01. 8: H NMR (CDCl3,
300 MHz) d 5.61 (d, J=1.5 Hz, 1H), 4.98–5.11 (m, 2H), 2.58
(dd, J=8.1, 7.5 Hz, 2H), 2.11 (dd, J=15.3, 7.5 Hz, 2H), 1.91–
2.03 (m, 4H), 1.85–1.87 (m, 3H), 1.60 (d, J=1.2 Hz, 3H),
1.53–1.54 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 171.79,
163.51, 135.99, 131.31, 124.31, 123.30, 115.74, 39.68, 33.64,
26.70, 26.65, 25.70, 25.65, 17.64, 15.86.
15. Buckingham, J.; Macdonald, F. Dictionary of Organic
Compounds; Chapman & Hall: London, 1996; 9 vols., and
references therein.
16. Slama, K.; Romanuk, M.; Sorm, F. Biol. Bull. 1969, 136, 91.
17. Uematsu, T.; Shidoji, Y. Gifu Daigaku Igakubu Kibo 1996,
44, 415.
18. Budt, K. H.; Vatele, J. M.; Kishi, Y. J. Am. Chem. Soc.
1986, 108, 6080.
19. Robbins, W. E.; Thompson, M. J.; Svoboda, J. A.;
Shortino, T. J.; Cohen, C. F.; Dutky, S. R.; Duncan, O. J., III.
Lipids 1975, 10, 353.
20. Yamatsu, I.; Inai, Y.; Abe, S.; Watanabe, H.; Igarashi, T.;
Shiojiri, H.; Tanabe, Y.; Hara, K. Chem. Abstr. 1982, 96, 6909.
Fr. Patent 2,463,122, 1981.
21. Sato, N. U.; Sugano, M.; Matsunaga, S.; Fusetani, N.
Tetrahedron Lett. 1999, 40, 719.