Synthesis of (±)-Lotthanongine, a Novel Natural Product with a Flavan-Indole Hybrid Structure

Keisuke Hatakeyama; Ken Ohmori; Keisuke Suzuki

doi:10.1055/s-2005-868485

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Synlett 2005(8): 1311-1315
DOI: 10.1055/s-2005-868485

LETTER

Synthesis of (±)-Lotthanongine, a Novel Natural Product with a Flavan-Indole Hybrid Structure

Keisuke Hatakeyama, Ken Ohmori, Keisuke Suzuki*
Department of Chemistry, Tokyo Institute of Technology, and SORST-JST Agency, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Fax: +81(3)57342788; e-Mail: ksuzuki@chem.titech.ac.jp;

Further Information

Publication History

Received 15 March 2005
Publication Date:
21 April 2005 (online)

Abstract
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Abstract

First total synthesis of lotthanongine (3), a natural product with a flavan-indole composite structure, has been achieved via the Lewis acid-catalyzed C-C bond formation between the catechin and the indole units.

Key words

catechin - indole - polyphenol - heterocycle - hybrid

References

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7

Afzelechin is available from Apin Chemicals in milligram quantities.

10

Compound 13: colorless amorphous solids. ¹H NMR (400 MHz, CDCl₃): δ = -0.52 (s, 3 H), -0.20 (s, 3 H), -0.18 (s, 3 H), -0.10 (s, 3 H), 0.69 (s, 9 H), 0.85 (s, 9 H), 3.80 (dd, 1 H, J = 10.0, 2.4 Hz), 4.98 (s, 2 H), 5.01 (d, 1 H, J = 2.4 Hz), 5.02 (s, 2 H), 5.09 (s, 2 H), 5.33 (d, 1 H, J = 10.0 Hz), 6.19 (d, 1 H, J = 2.2 Hz), 6.21 (d, 1 H, J = 2.2 Hz), 6.95 (d, 2 H, J = 8.8 Hz), 7.28-7.44 (m, 17 H). ¹³C NMR (100 MHz, CDCl₃): δ = -5.7, -5.3, -4.59, -4.58, 17.9, 18.4, 25.8, 26.0, 63.2, 70.0, 70.1, 70.2, 73.7, 76.1, 92.8, 94.1, 106.8, 114.6, 127.3, 127.6, 127.77, 127.82, 128.01, 128.04, 128.47, 128.52, 128.6, 129.2, 132.1, 136.6, 136.7, 137.1, 155.9, 157.2, 158.6, 160.5. IR (KBr): 3066, 3033, 2927, 2856, 1616, 1593, 1514, 1377, 1250, 1151, 1076, 883, 837, 775, 673 cm^-1. Anal. Calcd for C₄₈H₆₀O₆Si₂: C, 73.05; H, 7.66. Found: C, 72.87; H, 7.86.

16

Compound 21: colorless powders, mp 234-236 °C. ¹H NMR (400 MHz, DMSO): δ = 2.81 (br t, 2 H, J = 7.3 Hz), 3.43 (br td, 2 H, J = 7.3, 5.6 Hz), 5.09 (s, 2 H), 5.13 (s, 2 H), 6.47 (d, 1 H, J = 16.1 Hz), 6.72 (dd, 1 H, J = 8.5, 2.2 Hz), 6.90 (br d, 1 H, J = 2.2 Hz), 7.00 (br s, 1 H), 7.03 (d, 2 H, J = 8.6 Hz), 7.27-7.52 (m, 14 H), 8.10 (br t, 1 H, J = 5.6 Hz), 10.6 (br s, 1 H). ¹³C NMR (100 MHz, DMSO): δ = 25.4, 39.6, 69.3, 69.5, 96.0, 109.1, 111.8, 115.2, 118.9, 120.0, 121.4, 121.9, 127.5, 127.6, 127.7, 127.9, 128.4, 128.5, 129.0, 136.8, 137.7, 138.1, 154.4, 159.3, 165.1. IR (KBr): 3224, 1645, 1601, 1539, 1510, 1452, 1174, 694 cm^-1. Anal. Calcd for C₃₃H₃₀N₂O₃: C, 78.86; H, 6.02; N, 5.57. Found: C, 78.94; H, 5.91; N, 5.43.

18

Compound 3: ¹H NMR (500 MHz, CD₃OD): δ = 2.98-3.10 (m, 2 H), 3.47-3.55 (m, 1 H), 3.69-3.77 (m, 1 H), 4.15 (dd, 1 H, J = 9.6, 5.7 Hz), 4.67 (d, 1 H, J = 5.7 Hz), 4.95 (d, 1 H, J = 9.6 Hz), 5.95 (d, 1 H, J = 2.4 Hz), 6.00 (d, 1 H, J = 2.4 Hz), 6.27 (d, 1 H, J = 15.7 Hz), 6.55 (dd, 1 H, J = 8.5, 2.2 Hz), 6.74 (d, 1 H, J = 2.2 Hz), 6.77 (d, 2 H, J = 8.7 Hz), 6.78 (d, 2 H, J = 8.7 Hz), 7.24 (d, 2 H, J = 8.7 Hz), 7.27 (d, 2 H, J = 8.7 Hz), 7.33 (d, 1 H, J = 8.5 Hz), 7.35 (d, 1 H, J = 15.7 Hz), 9.30 (br s, 1 H). ¹³C NMR (125 MHz, CD₃OD): d = 25.3, 36.2, 41.3, 71.8, 79.6, 95.8, 96.8, 97.8, 102.9, 109.6, 111.7, 116.1, 116.7, 118.7, 119.4, 123.9, 127.9, 130.2, 130.6, 131.7, 133.9, 138.6, 141.5, 153.6, 157.5, 158.1, 158.5, 159.1, 160.4, 169.3. IR (KBr): 3300, 1647, 1514, 1458, 1227, 1146, 829 cm^-1. Anal. Calcd for C₃₄H₃₀N₂O₈: C, 68.68; H, 5.09; N, 4.71. Found: C, 68.41; H, 5.38; N, 4.42.

19

Compound 24: ¹H NMR (400 MHz, CD₃OD): δ = 2.90-3.05 (m, 1 H), 3.05-3.20 (m, 1 H), 3.46-3.58 (m, 1 H), 3.64-3.78 (m, 1 H), 4.08 (dd, 1 H, J = 9.8, 8.8 Hz), 4.33 (d, 1 H, J = 8.8 Hz), 4.62 (d, 1 H, J = 9.8 Hz), 5.95 (d, 1 H, J = 2.4 Hz), 5.98 (d, 1 H, J = 2.4 Hz), 6.38 (d, 1 H, J = 15.9 Hz), 6.52 (dd, 1 H, J = 8.6, 2.4 Hz), 6.66 (d, 1 H, J = 2.4 Hz), 6.75 (d, 2 H, J = 8.6 Hz), 6.81 (d, 2 H, J = 8.8 Hz), 7.25 (d, 2 H, J = 8.6 Hz), 7.27 (d, 1 H, J = 8.6 Hz), 7.33 (d, 2 H, J = 8.8 Hz), 7.37 (d, 1 H, J = 15.9 Hz), 8.02 (br s, 1 H), 9.52 (br s, 1 H). ¹³C NMR (100 MHz, CD₃OD): δ = 25.3, 41.3, 41.8, 75.1, 83.4, 96.6, 97.7, 97.9, 104.1, 109.3, 110.6, 116.1, 116.7, 118.8, 119.0, 123.6, 127.9, 130.3, 130.6, 131.0, 136.9, 138.6, 141.5, 153.5, 158.4, 158.6, 158.8, 159.0, 160.4, 169.3. IR (KBr): 3326, 1647, 1604, 1516, 1458, 1234, 1173, 1145, 1068, 831 cm^-1. Anal. Calcd for C₃₄H₃₀N₂O₈: C, 68.68; H, 5.09; N, 4.71. Found: C, 68.43; H, 5.38; N, 4.46.