K.-i. Oyama et al. / Tetrahedron Letters 49 (2008) 3176–3180
3179
Table 2
References and notes
1. (a) Haslam, E. Practical Polyphenolics; Cambridge University Press,
1998; (b) Rice-Evans, C. A.; Miller, N. J.; Paganga, G. Free Radical
Biol. Med. 1996, 20, 933–956; (c) Harborne, J. B.; Williams, C. A.
Phytochemistry 2000, 55, 481–504; (d) Ferreira, D.; Li, X.-C. Nat.
Prod. Rep. 2000, 17, 193–212; (e) Middleton, E., Jr. Pharmacol. Rev.
2000, 52, 673–751; (f) Mackenzie, G. G.; Carrasquedo, F.; Delfino, J.
M.; Keen, C. L.; Fraga, C. G.; Oteiza, P. I. FASEB J. 2004, 18, 167–
169.
2. Although an oligomer such as a 22-mer was also reported,2d most
cases are from dimer to about 15-mer2a,3: (a) Hammerstone, J. F.;
Lazarus, S. A.; Mitchell, A. E.; Rucker, R.; Schmitz, H. H. J. Agric.
Food Chem. 1999, 47, 490–496; (b) Yang, Y.; Chien, M. J. Agric. Food
Chem. 2000, 48, 3990–3996; (c) Wollgast, J.; Pallaroni, L.; Agazzi, M.-
E.; Anklam, E. J. Chromatogr., A 2001, 926, 211–220; (d) Es-Safi, N.-
E.; Guyot, S.; Ducrot, P.-H. J. Agric. Food Chem. 2006, 54, 6969–
6977.
OBn
OBn
OBn
BnO
O
OAc
OBn
BnO
OBn
OBn
O
Lewis acid
CH2Cl2
1a
OAc
OBn
OBn
n
BnO
O
OAc
OBn OAc
3. (a) Ariga, T.; Asao, Y. Agric. Biol. Chem. 1981, 45, 2709–2712; (b)
Ariga, T.; Koshiyama, I.; Fukushima, D. Agric. Biol. Chem. 1988, 55,
2717–2722; (c) Yoshida, K.; Kondo, T.; Ito, M.; Kondo, T. ITE Lett.
2005, 6, 19–24.
4. Our unpublished result: The procyanidin oligomers (up to 13-mer)
were observed in the extract from red adzuki seed coat (Vigna
angularis) by ESI-Q-TOF MS.
a
The product was a mixture of procyanidin oligomers.
Max DP was estimated by MALDI-TOF-MS using 2,5-dihydroxy-
b
benzoic acid as matrix.
c
Parentheses indicate the DPn which was estimated by size-exclusion
5. (a) Kawamoto, H.; Nakatsubo, F.; Murakami, K. Mokuzai Gakkai-
chromatography (SEC, polystyrene standards, CHCI3).
shi. 1991, 37, 488–493; (b) Tuckmantel, W.; Kozikowski, A. P.;
¨
Romanczyk, L. J., Jr. J. Am. Chem. Soc. 1999, 121, 12073–12081; (c)
Kozikowski, A. P.; Tuckmantel, W.; Bo¨ttcher, G.; Romanczyk, L. J.,
¨
Jr. J. Org. Chem. 2000, 65, 5371–5381; (d) Arnaudinaud, V.; Nay, B.;
The maximum degree of polymerization (max DP) detected
by MALDI-TOF-MS was 15 and the number average
degree of polymerization (DPn) measured by SEC was 7.4
(Table 2, entry 2).20 Sc(OTf)3 also gave a similar result.
In summary, we designed and prepared the 4-acetoxy-3-
acetylcatechin derivatives (1a,b) as a monomer unit for
procyanidin synthesis. 1a,b showed a high efficiency in both
step-wise condensation with TMSOTf and self-condensa-
tion with B(C6F5)3 to give procyanidin oligomers. Further-
more, the structure of a novel procyanidin-trimer from red
adzuki bean, Vigna angularis, was clarified using the
synthesized authentic samples. The synthesis of various
procyanidin oligomers according to the above-mentioned
method and the structural identification of polyphenols
from natural source are in progress.
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Nuhrich, A.; Deffieux, G.; Merillon, J.-M.; Monti, J. -P.; Vercauteren,
J. Tetrahedron Lett. 2001, 42, 1279–1281; (e) Kozikowski, A. P.;
Tuckmantel, W.; Hu, Y. J. Org. Chem. 2001, 66, 1287–1296; (f) Saito,
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A.; Nakajima, N.; Tanaka, A.; Ubukata, M. Biosci. Biotechnol.
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Tanaka, A.; Ubukata, M.; Nakajima, N. Synlett 2004, 1069–1073; (i)
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4790; (k) Mohri, Y.; Sagehashi, M.; Yamada, T.; Hattori, Y.;
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6. (a) Kawamoto, H.; Nakatsubo, F.; Murakami, K. J. Wood. Chem.
Technol. 1990, 10, 59–74; (b) Yoneda, S.; Kawamoto, H.; Nakatsubo,
F. J. Chem. Soc., Perkin Trans. 1 1997, 1025–1030.
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spring meetings (The Chemical Society of Japan) 2001, 1073; (b)
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Acknowledgments
8. The details of the substitution reaction of flavan skeleton were
reported by Suzuki et al. They described that the stereochemistry of
C4-position has no influence on the stereoselectivity and concluded
that this reaction is SN1-like reaction.
9. Nakamura, S.; Oyama, K.-I.; Kondo, T.; Yoshida, K. Heterocycles
2007, 73, 451–460.
This work was financially supported by the Ministry of
Education, Culture, Sports, Science and Technology,
Japan ((B) No. 16370021, the 21st Century COE Program
No. 14COEB01-00, Creative Scientific Research No.
16GS0206, Global COE in Chemistry, Nagoya University,
Priority Areas No. 18032037, and Young Scientists (B) No.
18780086).
10. Compound 5a (J2,3 = 9.3 Hz, J3,4 = 5.5 Hz), 5b (J2,3 = 2.4 Hz,
J3,4 = 1.4 Hz).
11. Compound 1a was already reported by Suzuki et al., but they carried
out only a model study (one example) in the presence of BF3ꢁEt2O.7b
12. 1.5 equiv of 4a to 2 was used. The reaction temperature was raised
gradually from ꢀ78 °C to ꢀ10 °C. The products were decomposed at
rt in the reaction mixture.
13. After acetylation, the structural identification was performed by
various 1D and 2D (COSY, NOESY, HMQC, and HMBC) NMR
experiments.
Supplementary data
1
Copies of H NMR spectra of 12 and the acetate of the
natural sample from red adzuki bean. Supplementary data
associated with this article can be found, in the online