3008
K. Harada et al. / Tetrahedron Letters 52 (2011) 3005–3008
H2, Pd-C, benzene, 35% from 20
LiAlH4, THF, 56% from 22
O
O
RO
HO
O
O
NaOMe, MeOH, 77% from 24
OMe
O
OMe
O
20: R = Bn
22: R = Bz
24: R = Ts
(2S,3R,4S,5S)-2
[α]D −134.3
Scheme 5. Synthesis of the (2S,3R,4S,5S)-isomer 2 of (À)-talaumidin.
5. Zhai, H.; Inoue, T.; Moriyama, M.; Esumi, T.; Mitsumoto, Y.; Fukuyama, Y. Biol.
Pharm. Bull. 2005, 28, 289–293.
6. Esumi, T.; Hojyo, D.; Zhai, H.; Fukuyama, Y. Tetrahedron Lett. 2006, 47, 3979–
3983.
7. Fukuyama, Y.; Harada, K.; Esumi, T.; Hojyo, D.; Kujime, Y.; Kubo, N.; Hioki, H.
Heterocycles 2008, 76, 551–567.
8. Harada, K.; Kubo, N.; Tanabe, K.; Kubo, M.; Esumi, T.; Hioki, H.; Fukuyama, Y.
Heterocycles 2011, 82, 1127–1132.
furan ring with the 5S-configuration. In addition, the present syn-
thetic study led to the conclusion that the absolute configurations
of natural lignans (+)- and (–)-chicanines should be changed so
that they are expressed as antipode to each other. Neurotrophic
activity of 2 will be reported in due course and further synthetic
studies on the remaining stereoisomers of 1 are now in progress.
9. Liu, J.-S.; Huang, M.-F.; Gao, Y.-L. Can. J. Chem. 1981, 59, 1680–1684.
10. (a) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127–2129;
(b) Evans, D. A.; Takacs, J. M.; McGee, L. R.; Ennis, M. D.; Mathre, D. J.; Bartoli, J.
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Acknowledgments
We thank Professor Emi Okuyama (Josai International Univer-
sity) for providing us the CD spectrum of the natural (À)-chicanine
and Dr. Yasuko Okamoto for measuring the MS spectra. This work
was supported by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science, and Technology of
Japan (22590029, 22790030), and MEXT-Senryaku.
13. (a) Mitsunobu, O. Synthesis 1981, 1–28; (b) Hughes, D. L. Org. React. 1992, 42,
335–656.
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Supplementary data
Supplementary data (experimental procedures and character-
ization data) associated with this article can be found, in the online
17. (a) Sakamoto, I.; Kaku, H.; Tsunoda, T. Chem. Pharm. Bull. 2003, 51, 474–476; (b)
Tsunoda, T.; Takagi, H.; Takaba, D.; Kaku, H.; Ito, S. Tetrahedron Lett. 2000, 41,
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18. The (2R,3R,4S,5R)-configuration of 21 corresponds to the enantiomer of
(2S,3S,4R,5S)-talaumidin in Ref. 6. The 1H NMR, 13C NMR, IR, and MS spectra
of debenzyl-21 were consistent with those of 2S,3S,4R,5S-isomer 1b, and the
References and notes
optical rotation of debenzyl-21 ([
2S,3S,4R,5S-isomer ([
À46.5).
a
]
+43.5) was opposite to that of the
D
a
]
D
1. Hefti, F. Annu. Rev. Pharmacol. Toxicol. 1997, 37, 239–267.
2. Bäckman, C.; Rose, G. M.; Hoffer, B. J.; Henry, M. A.; Bartus, R. T.; Friden, P.;
Granholm, A.-C. J. Neurosci. 1996, 16, 5437–5442.
19. Data of 2: Colorless amorphous; 1H NMR (400 MHz, CDCl3) d 0.61 (3H, d,
J = 7.1 Hz), 1.00 (3H, d, J = 6.6 Hz), 2.37–2.46 (2H, m), 3.89 (3H, s), 4.62 (1H, d,
J = 9.3 Hz), 5.43 (1H, d, J = 4.4 Hz), 5.52 (1H, s), 5.94 (1H, d, J = 1.5 Hz), 5.95 (1H,
d, J = 1.5 Hz), 6.77 (1H, dd, J = 8.1, 1.7 Hz), 6.78 (1H, d, J = 7.9 Hz), 6.83 (1H, dd,
J = 8.1, 1.7 Hz), 6.88 (1H, d, J = 7.9 Hz), 6.92 (1H, d, J = 1.7 Hz), 6.93 (1H, d,
J = 1.7 Hz); 13C NMR (100 MHz, CDCl3) d 47.7, 56.0, 84.8, 85.7, 100.9, 106.5,
108.0, 108.7, 114.0, 118.8, 119.6, 132.5, 137.2, 144.3, 146.3, 146.9, 147.9; IR
(ATR) 1037, 1244, 1444, 1288, 1514, 2963, 3463 cmÀ1; CIMS m/z (rel. int.) 343
(100, M+1), 219 (55), 190 (63), 41 (87); HRCIMS calcd 343.1546 for C20H23O5,
3. For recent reports, see: (a) Fukuyama, Y.; Kubo, M.; Esumi, T.; Harada, K.; Hioki,
H. Heterocycles 2010, 81, 1571–1602; (b) Kubo, M.; Kishimoto, Y.; Harada, K.;
Hioki, H.; Fukuyama, Y. Bioorg. Med. Chem. Lett. 2010, 20, 2566–2571; (c) Kubo,
M.; Okada, C.; Huang, J.-M.; Harada, K.; Hioki, H.; Fukuyama, Y. Org. Lett. 2009,
11, 5190–5193; (d) Takaoka, S.; Takaoka, N.; Minoshima, Y.; Huang, J.-M.; Kubo,
M.; Harada, K.; Hioki, H.; Fukuyama, Y. Tetrahedron 2009, 65, 8354–8361; (e)
Tang, W.; Kubo, M.; Harada, K.; Hioki, H.; Fukuyama, Y. Bioorg. Med. Chem. Lett.
2009, 19, 882–886; (f) Tang, W.; Hioki, H.; Kubo, M.; Harada, K.; Fukuyama, Y. J.
Nat. Prod. 2008, 71, 1760–1763; (g) Moriyama, M.; Huang, J.-M.; Yang, C.-S.;
Kubo, M.; Harada, K.; Hioki, H.; Fukuyama, Y. Chem. Pharm. Bull. 2008, 56,
1201–1204.
found: 343.1540; [
a
]
À134.3 (c 1.01, CHCl3); CD (MeOH) [ ] (nm): À6394
U
D
(220, max), À17056 (236, min), À324 (258, max), À3160 (288, min).
20. We have found no studies that have unambiguously determined the absolute
configuration of (+)-galcatin.
21. Sadhu, S. K.; Okuyama, E.; Fujimoto, H.; Ishibashi, M. Chem. Pharm. Bull. 2003,
51, 595–598.
4. Zhai, H.; Nakatsukasa, M.; Mitsumoto, Y.; Fukuyama, Y. Planta Med. 2004, 70,
598–602.