Efficient Stereoselective Synthesis of Proanthocyanidin Trimers with ­TMSOTf-Catalyzed Intermolecular Condensation

Akiko Saito; Akira Tanaka; Makoto Ubukata; Noriyuki Nakajima

doi:10.1055/s-2004-822905

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2004(6): 1069-1073
DOI: 10.1055/s-2004-822905

LETTER

Efficient Stereoselective Synthesis of Proanthocyanidin Trimers with TMSOTf-Catalyzed Intermolecular Condensation [1]

Akiko Saito*^a, Akira Tanaka^b, Makoto Ubukata^c, Noriyuki Nakajima*^d
^a Biotechnology Center, Toyama Prefecture, Japan
^b Department of Bioresources Science, College of Technology, Toyama Prefectural University, Japan
^c Graduate School of Agriculture, Hokkaido University, Japan
^d Biotechnology Center, Toyama Prefectural University, Kosugi, Toyama 939-0398, Japan
Fax: +81(766)562498; e-Mail: nori@pu-toyama.ac.jp;

Further Information

Publication History

Received 29 January 2004
Publication Date:
08 April 2004 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

A stereoselective synthesis of seven benzylated proanthocyanidin trimers with TMSOTf-catalyzed condensation reaction is described. In particular, epicatechin-(4β-8)-epicatechin-(4β-8)-epicatechin trimer (procyanidin C1), catechin-(4α-8)-catechin-(4α-8)-catechin trimer (procyanidin C2), epicatechin-(4β-8)-epicatechin-(4β-8)-catechin trimer and epicatechin-(4β-8)-catechin-(4α-8)-epicatechin trimer derivatives were obtained in excellent yields. The structure of benzylated procyanidin C2 was confirmed by comparing the ¹H NMR spectra of protected procyanidin C2 that was synthesized by two different condensation approaches. Finally, deprotection of (+)-catechin and (-)-epicatechin trimers derivatives gave four natural procyanidin trimers in good yields.

Key words

polyphenol - condensed tannin - oligomeric flavonoid - catechin trimer - C-type procyanidin

1

This report is Part 6 in the series ‘Synthetic studies of proanthocyanidins’.

References

2 Harborne JB. The Flavonoids: Advances in Research from 1986 Chapman and Hall; London: 1993.

Google Scholar
3 Harborne JB. Baxter H. The Handbook of Natural Flavonoids John Wiley and Sons; New York: 1999.

Google Scholar
4 Ariga T. Koshiyama I. Fukushima D. Agric. Biol. Chem. 1988, 52: 2717

Crossref Google Scholar
5 Zhao J. Wang J. Chen Y. Agarwal R. Carcinogenesis 1999, 20: 1737

Crossref Google Scholar
6 Baba S. Osakabe N. Natsume M. Terao J. Free Radical Biol. Med. 2002, 33: 142

Crossref Google Scholar
7 Sano A. Yamakoshi J. Tokutake S. Tobe K. Kubota Y. Kikuchi M. Biosci., Biotechnol., Biochem. 2003, 67: 1140

Crossref PubMed Google Scholar
8 Saito A. Nakajima N. Tanaka A. Ubukata M. Heterocycles 2003, 61: 287

Crossref Google Scholar
9 Part 5: Saito A. Nakajima N. Matsuura N. Tanaka A. Ubukata M. Heterocycles 2004, 62: 479

Crossref Google Scholar
10 Saito A. Nakajima N. Tanaka A. Ubukata M. Tetrahedron Lett. 2003, 44: 5449

Crossref Google Scholar
11a Thompson RS. Jacques D. Haslam E. Tanner RJN. J. Chem. Soc., Perkin Trans. 1 1972, 1387

Crossref Google Scholar
11b Kolodziej H. Phytochemistry 1989, 28: 3487

Crossref Google Scholar
11c Hsu F. Nonaka G. Nishioka I. Chem. Pharm. Bull. 1985, 33: 3293

Crossref Google Scholar
11d Nonaka G. Hsu F. Nishioka I. J. Chem. Soc., Chem. Commun. 1981, 781

Crossref Google Scholar
11e Delcour A. Vercruysse AR. J. Inst. Brew. 1986, 92: 244

Crossref Google Scholar
11f Balas L. Vercauteren J. Magn. Reson. Chem. 1994, 32: 386

Crossref Google Scholar
11g Hemingway RW. Foo LY. Porter LJ. J. Chem. Soc., Perkin Trans. 1 1982, 1209

Crossref Google Scholar
12 Saito A. Nakajima N. Tanaka A. Ubukata M. Tetrahedron 2002, 58: 7829

Crossref Google Scholar
17 Kolodziej H. Plant Polyphenols Hemingway RW. Laks PE. Plenum Press; New York: 1992. p.295-319

Google Scholar
18 Balas L. Vercauteren J. Magn. Reson. Chem. 1995, 33: 85

Crossref Google Scholar
22 Kozikowski AP. Tückmantel W. Hu Y. J. Org. Chem. 2003, 68: 1641

Crossref Google Scholar

1

This report is Part 6 in the series ‘Synthetic studies of proanthocyanidins’.

13

In this condensation reaction, excess amount (4.0-4.5 equiv) of a monomer nucleophile was used to avoid higher oligomer formation.

14

Data for 7c: [α]_D ²⁶ -82.2 (c 0.12, CHCl₃). ¹H NMR (400 MHz, CDCl₃, 0.83:0.17 mixture of rotational isomers) δ (major isomer) = 7.35-6.35 (57.27 H, m), 6.11 (0.83 H, s), 6.10 (0.83 H, d, J = 2.2 Hz), 6.02 (0.83 H, d, J = 2.2 Hz), 6.00 (0.83 H, s), 5.17-4.33 (21.58 H, m), 4.19 (0.83 H, d, J = 8.8 Hz), 3.97-3.86 (1.66 H, m), 3.73-3.68 (0.83 H, m), 3.53 (0.83 H, d, J = 9.0 Hz), 3.03 (0.83 H, dd, J = 6.1 and 16.1 Hz), 2.89 (0.83 H, d, J = 9.6 Hz), 2.78 (0.83 H, dd, J = 9.7 and 16.1 Hz), 1.31 (0.83 H, d, J = 2.6 Hz, OH), 1.78 (0.83 H, d, J = 3.9 Hz, OH), 1.07 (0.83 H, d, J = 3.7 Hz, OH); δ (minor isomer) = 7.35-6.35 (11.22 H, m), 6.28 (0.17 H, d, J = 1.7 Hz), 6.21 (0.17 H, d, J = 8.3 Hz), 6.18 (0.17 H, s), 6.15 (0.17 H, s), 6.05 (0.17 H, d, J = 2.2 Hz), 5.97 (0.17 H, d, J = 2.2 Hz), 5.80 (0.17 H, dd, J = 1.7 and 8.3 Hz), 5.17-4.33 (5.27 H, m), 4.06-3.86 (0.34 H, m), 3.73-3.68 (0.17 H, m), 3.58-3.57 (0.17 H, m), 2.93 (0.17 H, d, J = 10.0 Hz), 2.66 (0.17 H, m), 2.37-2.32 (0.17 H, m), 1.44-1.41 (0.17 H, m, OH), 1.36-1.34 (0.17 H, m, OH), 1.20-1.17 (0.17 H, m, OH). ¹³C NMR (100 MHz, CDCl₃): δ (major isomer) = 157.9, 157.8, 156.7, 155.5, 155.4, 155.1, 155.1, 154.9, 153.8, 149.2, 149.1, 149.0, 148.8 (× 2), 148.5, 137.6, 137.4, 137.4, 137.4, 137.3, 137.2, 137.2, 137.1, 137.1, 137.0, 136.0, 132.4, 132.3, 131.7, 128.8-126.9 (C × 37), 121.1, 120.6, 120.5, 115.0, 114.8, 114.7, 114.5, 114.1, 113.6, 112.2, 109.4, 108.6, 102.4, 101.1, 94.7, 93.8, 92.0, 91.8, 81.7, 81.0, 80.4, 73.0, 72.9, 71.9-69.8 (C × 11), 68.4, 65.2, 37.5, 37.4, 28.4; minor isomer was not identified. FAB-MS: m/z (%) = 1947 (0.26) [M + H]⁺. FAB-HRMS calcd for C₁₂₉H₁₁₀O₁₈ [M + H]⁺: 1947.7770; found: 1947.7694.

15

Data for 7a: [α]_D ²⁵ -233.7 (c 0.38, EtOH) {lit. [11a] [α]₅₇₈ -173 (c 1.03, EtOH)}; HPLC R_t 7a = 18.8 min. FAB-MS: m/z (%) = 890 (12.5), 889 (21.5) [M + Na]⁺, 888 (14.7), 887 (12.4), 868 (6.9), 867 (12.6) [M + H]⁺, 866 (10.9), 328 (100). FAB-HRMS calcd for C₄₅H₃₈O₁₈Na [M + Na]⁺: 889.1956; found: 889.2018.

16

HPLC analysis conditions: Mightysil^® RP-18 GP column (Kanto Chemical Co. Inc., Japan; 250 × 4.6 mm, 5µm); solvent (A) 0.1% CF₃CO₂H in MeCN, (B) 0.1% CF₃CO₂H in H₂O: Elution was done with a linear gradient 5% to 100% A in 40 min (flow rate: 0.5 mL/min.).

19

Data for 1a: [α]_D ²⁵ +56.9 (c 0.30, EtOH) {lit. [11c] [α]_D +76.9}; HPLC R_t 1a = 20.5 min. ¹H NMR (400 MHz, CD₃COCD₃/D₂O, 15/1): δ = 7.13-6.69 (9 H, br), 6.10-5.83 (4 H, br), 5.30-5.05 (1 H, br), 5.04-5.03 (1 H, br), 4.89-4.54 (3 H, br), 4.16-3.95 (3 H, br), 2.75-2.60 (1 H, br), 2.58-2.51 (1 H, br). FAB-MS: m/z (%) = 889 (12.8) [M + Na]⁺, 888 (7.1), 887 (5.8), 867 (9.0) [M + H]⁺, 866 (6.7), 329 (100). FAB-HRMS calcd for C₄₅H₃₈O₁₈Na [M + Na]⁺: 889.1956; found: 889.1927.

20

Data for 4a: [α]_D ²⁴ -112.6 (c 0.40, MeOH) {lit. [11d] [a]_D ²⁷
-97.6 (c 1.0, MeOH)}; HPLC R_t 4a = 20.3 min. FAB-MS: m/z (%) = 890 (2.2), 889 (4.0) [M + Na]⁺, 888 (3.3), 887 (2.1), 868 (2.2), 867 (3.9) [M + H]⁺, 866 (3.1), 613 (4.2), 483 (11.7), 482 (25.2), 460 (48.2), 328 (100), 306 (100). FAB-HRMS calcd for C₄₅H₃₈O₁₈Na [M + Na]⁺: 889.1956; found: 889.1882.

21

Data for 2a: [α]_D ²⁷ +59.3 (c 0.30, MeOH) {lit. [α]_D +70.4 (c 2.2, MeOH)}; HPLC²⁰ R_t 2a = 22.0 min. FAB-MS: m/z (%) = 890 (1.9), 889 (3.3) [M + Na]⁺, 888 (2.2), 887 (1.7), 868 (1.6), 867 (3.3) [M + H]⁺, 866 (2.5), 613 (8.3), 482 (25.5), 459 (45.8), 328 (100), 306 (100). FAB-HRMS calcd for C₄₅H₃₈O₁₈Na [M + Na]⁺: 889.1956; found: 889.2031.