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potential for producing nalanthalide analogues in enan-
tiomerically pure forms due to its generality and flexibi-
lity. These efforts are currently underway.
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Acknowledgments
11. For recent reviews on the [2,3]-Wittig rearrangement, see:
(a) Nakai, T.; Tomooka, K. Pure Appl. Chem. 1997, 69,
595–600; (b) Nakai, T.; Mikami, K. Org. React. 1994, 46,
105–209; (c) Mikami, K.; Nakai, T. Synthesis 1991, 594–
604; (d) Marshall, J. A. The Wittig Rearrangement. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon: Oxford, 1991; Vol. 3, pp 975–1014.
12. The configuration of the newly formed C9 stereocenter in
19 was confirmed by NOESY experiments as depicted in
the following figure, where clear NOE interactions
between the angular methyl group (C10–Me) and C9–H,
C20–Ha and between C9–H and C20–Ha were observed,
respectively.
We are especially grateful to Dr. Sheo B. Singh (Merck
Research Laboratories) for providing us with copies of
1
the H and 13C NMR spectra of natural (ꢀ)-nalanthal-
ide (1). We also thank Dr. N. Sugimoto (National Insti-
tute of Health Sciences) and Dr. N. Kawahara
(National Institute of Health Sciences), for measure-
ments of HRMS and assistance with NMR experiments.
This work was supported in part by Grants-in-Aid for
High Technology Research Program and for Scientific
Research on Priority Areas (17035073) from the Minis-
try of Education, Culture, Sports, Science, and Techno-
logy of Japan.
NOEs
Ha
20
Me
H
Me
10
References and notes
9
Hb
8
TBSO
1. Goetz, M. A.; Zink, D. L.; Denzeny, G.; Dombrowski, A.;
Polishook, J. D.; Felix, J. P.; Slaughter, R. S.; Singh, S. B.
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OH
H
H
Me
Me
19
2. It is reported that 1 blocked the 86Rb+ efflux in CHO-
Kv1.3 cells with an IC50 value of 3.9 lM (Ref. 1).
This remarkable stereoselectivity can be rationalized by the
consideration that the attack of the in situ generated
carbanion on the C9 olefinic carbon occurred exclusively
from the less hindered a-face of the molecule under an
influence of the b-oriented axial methyl group at C10.
13. Data for 5: Colorless viscous oil, ½aꢁ2D0 +42.4 (c 0.81, CHCl3).
IR (neat) 2930, 2857, 1719, 1460, 1385, 1254, 1101,
3. Schmalhofer, W. A.; Bao, J.; McManus, O. B.; Green, B.;
Matyskiela, M.; Wunderler, D.; Bugianesi, R. M.; Felix, J.
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1065, 937, 891, 837, 774, 619, 523, 415 cmꢀ1 1H NMR
.
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Niculescu, T.; Niculescu, F.; Mullen, K. M.; Allie, R.;
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5. The absolute configuration of 1 has not been discussed in
the literature (Ref. 1).
(500 MHz, CDCl3): d 0.03 (3H, s), 0.04 (3H, s), 0.77 (3H, s),
0.87 (9H, s), 0.97 (3H, s), 1.15–1.30 (3H, m), 1.35–1.40 (1H,
m), 1.44–1.50 (1H, m), 1.50–1.58 (4H, m), 1.61 (3H, s), 1.68
(3H, s), 1.80–1.88 (2H, m), 2.20–2.30 (1H, m), 2.40–2.47
(1H, m), 2.61 (1H, d, J = 3.8 Hz), 3.52 (1H, dd, J = 4.3,
11.1 Hz), 4.77 (1H, br s), 4.94 (1H, t, J = 1.8 Hz), 5.04 (1H,
br t, J = 7.0 Hz), 9.88 (1H, d, J = 3.9 Hz). 13C NMR
(125 MHz, CDCl3): d ꢀ5.0, ꢀ3.6, 17.8, 17.9, 18.0, 20.8, 21.6,
22.0, 25.9 (three carbons), 27.8, 33.0, 35.1, 36.1, 36.9, 38.9,
41.3, 41.8, 71.1, 73.5, 113.9, 124.6, 131.0, 142.2, 202.6.
HREIMS (m/z) calcd for C26H46O2Si (M+): 418.3267;
found 418.3253.
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Watanabe, K.; Nobeyama, A.; Suzuki, T. Tetrahedron
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conditions (tetrabutylammonium fluoride, THF, rt!
reflux) was unsuccessful. The c-pyrone moiety of 23 was
labile under these basic conditions.
16. Data for 1: amorphous white solid, mp 144–146 °C [lit.1
25
25
96.5–98 °C], ½aꢁD ꢀ48.3 (c 1.02, CHCl3) [lit.1 ½aꢁD ꢀ58.2 (c
0.275, CHCl3)]. IR (neat) 702, 735, 881, 982, 1026, 1240,
1252, 1317, 1375, 1417, 1458, 1599, 1670, 1732, 2854,
6. (a) Uchida, R.; Imasato, R.; Yamaguchi, Y.; Masuma, R.;
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2925 cmꢀ1. H NMR (500 MHz, CDCl3): d 0.86 (3H, s),
1
7. Zhang, F.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2002,
41, 1434–1437.
8. Watanabe, K.; Iwasaki, K.; Abe, T.; Inoue, M.; Ohkubo,
K.; Suzuki, T.; Katoh, T. Org. Lett. 2005, 7, 3745–3748.
0.96 (3H, s), 1.14–1.22 (1H, m), 1.22–1.33 (1H, m), 1.35–
1.40 (2H, m), 1.50–1.54 (1H, m), 1.61 (3H, s), 1.68 (3H, s),
1.70–1.78 (3H, m), 1.85–1.93 (1H, m), 1.89 (3H, s), 1.92–
2.00 (2H, m), 1.97 (1H, dd, J = 3.2, 11.9 Hz), 2.04 (3H, s),