J.-C. Kim et al. / Tetrahedron: Asymmetry 17 (2006) 3–6
5
O
O
O
Bi
O
O
O
O
O
O
NH
Bi
ꢀ
N
O
ꢃ
H
H
O
N
O
O
O
Bi
9
b
10b
O
1
5
O
O
O
O
O
O
O
OR
c
s
H
H
H
H
RO
O
O
O
O
O
O
1
1
6nR=H
7nR=Ac
u
(-)-sesamin 1b
Scheme 3. Reagents and conditions: (a) n-BuLi, succinyl chloride/THF, 0 ꢁC, 2 h, 86%; (b) (i) Bu
2
BOTf, DIPEA/CH
2
Cl
2
, ꢀ78 ꢁC, 7, 20 min; (ii)
KH
BF
2
PO
4
(aq), H
Cl
2
O
2
(28%)/MeOH, rt, 8 h, 88% (two steps); (c) DIBAL-H/THF, ꢀ25 ꢁC, 1 h, 45%; (d) Ac
2 3
O/pyridine, 48 h, 70%; (e) Et SiH,
3
ÆEt O/CH
2
2
2
, ꢀ78 ꢁC, 1 h, 58%.
1
0b was treated with dibutylboron triflate (Bu BOTf)16
S. Nat. Prod. Rep 1995, 12, 183–205; (d) Ward, R. S. Nat.
Prod. Rep. 1997, 14, 143–174; (e) Ward, R. S. Nat. Prod.
Rep 1999, 16, 75–96; (f) Whiting, D. A. Nat. Prod. Rep.
2
in the presence of DIPEA in CH Cl to generate the
2
2
1
5
(
Z)-enolate, which in situ was reacted stereoselectively
1
990, 7, 349–364.
with piperonal 7 at ꢀ78 ꢁC for 20 min.
2
. (a) Okuyama, E.; Suzumura, K.; Yamazaki, M. Chem.
Pharm. Bull. 1995, 43, 2200–2204; (b) Hashimoto, K.;
Yanagisawa, T.; Okui, Y.; Ikeya, Y.; Maruno, M.; Fujita,
T. Planta Med. 1994, 60, 124–127; (c) Takasaki, M.;
Konoshima, T.; Yasuda, I.; Hamano, T.; Tokuda, H. Biol.
Pharm. Bull. 1997, 20, 776–780.
3. Chiung, Y. M.; Hayashi, H.; Matsumoto, H.; Otani, T.;
Yoshida, K.; Huang, M. Y.; Chen, R. X.; Liu, J. R.;
Nakayama, M. J. Antibiot. 1994, 47, 487–491.
The mixture was then quenched with KH PO to afford
2
4
dilactone 15 in 95:5 dr selectivity (88% combined yield,
two steps). Dilactone 15 was treated with DIBAL-H in
THF at ꢀ25 ꢁC to give dilactol 16 (1:1 cis/trans ratio,
1
7
4
5% combined yield). Due to intermediate 16 being
unstable, its isolation, and characterization were prob-
lematic. Acetylation of 16 with acetic anhydride gave
diacetate 17 (70%), which could be easily isolated
and characterized. Reduction of dilactol 16 with Et SiH
9
a
4. (a) MacRae, W. D.; Towers, G. H. N. Phytochemistry
1
984, 23, 1207–1220; (b) Brown, R. C.; Bataille, C. J.;
Bruton, G.; Hinks, J. D.; Swain, N. A. J. Org. Chem. 2001,
6, 6719–6728.
. (a) Iwakami, S.; Ebizuka, Y.; Sankawa, U. Heterocycles
990, 30, 795–798; (b) Iwakami, S.; Wu, J. B.; Ebizuka, Y.;
3
and BF ÆEt O in CH Cl gave (ꢀ)-sesamin 1b in 58%
3
2
2
2
6
yield (Scheme 3).
5
1
Sankawa, U. Chem. Pharm. Bull. 1992, 40, 1196–1198.
. Ichikawa, K.; Kinoshita, T.; Nishibe, S.; Sankawa, U.
Chem. Pharm. Bull. 1986, 34, 3514–3517.
3
. Conclusion
6
7
In conclusion, a new and efficient method has been
developed for the synthesis of (+)-sesamin 1a and (ꢀ)-
sesamin 1b via a five-step route using a stereoselective al-
dol condensation in overall 22% and 20% yields, respec-
tively. This synthetic method is superior to those
reported in view of simplicity, enantiomeric excess,
and overall yield and should be useful in the synthesis
of lignans. All physical and spectral data for the synthet-
ically prepared (+)-sesamin 1a and (ꢀ)-sesamin 1b were
. Isolation: Bertram, S. H. Biochem. Zeit. 1928, 197, 433–
4
41; Structure: (a) Cohen, W. D. Rec. Trav. Chem. 1938,
57, 653–658; (b) Von Bruchhausen, F.; Gerhard, H. Ber.
1939, 72B, 830–838; Stereochemistry: Becker, E. D.;
Beroza, M. Tetrahedron Lett. 1962, 157–163.
8
. Beroza, M.; Schechter, M. S. J. Am. Chem. Soc. 1956, 78,
1
242–1247.
9
. (a) Pelter, A.; Ward, R. S.; Watson, D. J.; Collins, P.; Kay,
I. T. J. Chem. Soc., Perkin Trans. 1 1982, 175–181; (b)
Taylor, E. C.; Andrade, J. G.; Rall, G. J. H.; Steliou, K.;
Jagdmann, G. E., Jr.; McKillop, A. J. Org. Chem. 1981,
1
1,12
identical to those reported for the natural product.
4
6, 3078–3081; (c) Takano, S.; Ohkawa, T.; Tamori, S.;
Satoh, S.; Ogasawara, K. J. Chem. Soc., Chem. Commun.
988, 189–191; (d) Orito, K.; Yorita, K.; Suginome, H.
Acknowledgment
1
Tetrahedron Lett. 1991, 32, 5999–6002; (e) Suginome, H.;
Ishikawa, M.; Yorita, K.; Shimoyama, N.; Sasaki, T.;
Orito, K. J. Org. Chem. 1995, 60, 3052–3064; (f) Takeya,
T.; Ara, Y.; Tobinaga, S. Chem. Pharm. Bull. 1995, 43,
This work was supported by KOSEF (Grant No. RO5-
001-000-00237-0).
2
1
970–1976; (g) Samizu, K.; Ogasawara, K. Chem. Lett.
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