Synthesis of Isoprenyl Flavonoids: (+)-Denticulaflavonol, Macarangin, and Isomacarangin

Pilar Basabe; Mónica de Román; David Diez; Isidro S. Marcos; Olga Bodero; Araceli Blanco; Faustino Mollinedo; Julio G. Urones

doi:10.1055/s-2008-1072734

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Synlett 2008(8): 1149-1152
DOI: 10.1055/s-2008-1072734

LETTER

Synthesis of Isoprenyl Flavonoids: (+)-Denticulaflavonol, Macarangin, and Isomacarangin

Pilar Basabe*^a, Mónica de Román^a, David Diez^a, Isidro S. Marcos^a, Olga Bodero^a, Araceli Blanco^a, Faustino Mollinedo^b, Julio G. Urones^a
^a Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
Fax: +34(923)294574; e-Mail: pbb@usal.es;
^b Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain

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Publication History

Received 9 November 2007
Publication Date:
16 April 2008 (online)

Abstract
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Abstract

A straightforward synthesis of two natural C-alkylflavonoids: macarangin, isomacarangin, and the enantiomer of the natural (-)-denticulaflavonol, has been described.

Key words

isoprenyl flavonoids - denticulaflavonol - macarangin - isomacarangin - antitumour activity

References and Notes

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18

Physical Data of (+)-Denticulaflavonol (1) [α]_D ²² +15.0 (c 0.10, CHCl₃). IR (film): 3392, 2921, 2850, 1648, 1609, 1463, 1367, 1261, 1178, 1090 cm^-1. ¹H NMR (700 MHz, CDCl₃): δ = 12.10 (1 H, s, 5-OH), 8.12 (2 H, d, J = 8.8 Hz, H-2′, H-6′), 6.96 (2 H, d, J = 8.8 Hz, H-3′, H-5′), 6.56 (1 H, s, 3-OH), 6.47 (1 H, s, H-8), 6.16 (1 H, s, 7-OH), 5.27 (1 H, t, J = 7.6 Hz, H-14′′), 5.07 (1 H, s, 4′-OH), 4.80 (1 H, s, H_A-17′′), 4.48 (1 H, s, H_B-17′′), 3.48 (2 H, d, J = 7.6 Hz, H-15′′), 2.35 (1 H, m, H_A-7′′), 2.19 (1 H, m, H_A-12′′), 1.90 (1 H, m, H_B-7′′), 1.87 (1 H, m, H_B-12′′), 1.84 (3 H, s, H-16′′), 1.72 (1 H, m, H_A-1′′), 1.69 (1 H, m, H_A-6′′), 1.60 (1 H, m, H_A-11′′), 1.56 (1 H, m, H_A-2′′), 1.55 (1 H, m, H-9′′), 1.47 (1 H, m, H_B-2′′), 1.44 (1 H, m, H_B-11′′), 1.38 (1 H, m, H_A-3′′), 1.30 (1 H, m, H_B-6′′), 1.15 (1 H, m, H_B-3′′), 1.05 (1 H, m, H-5′′), 0.98 (1 H, m, H_B-1′′), 0.85 (3 H, s, H-18′′), 0.78 (3 H, s, H-19′′), 0.66 (3 H, s, H-20′′) ppm. ¹³C NMR (175 MHz, CDCl₃): δ = 175.3 (C-4), 161.7 (C-7), 157.7 (C-5), 157.2 (C-4’), 155.0 (C-9), 148.5 (C-8′′), 145.3 (C-2), 140.8 (C-13′′), 135.4 (C-3), 129.6 (C-2′, C-6′), 123.6 (C-1′), 120.5 (C-14′′), 115.6 (C-3′, C-5′), 109.3 (C-6), 106.2 (C-17′′), 103.5 (C-10), 94.3 (C-8), 56.0 (C-9′′), 55.5 (C-5′′), 42.1 (C-3′′), 39.6 (C-10′′), 39.0 (C-1′′), 38.5 (C-12′′), 38.3 (C-7′′), 33.6 (C-18′′), 33.5 (C-4′′), 24.4 (C-6′′), 21.7 (C-11′′, C-19′′), 21.4 (C-15′′), 19.4 (C-2′′), 16.4 (C-16′′), 14.5 (C-20′′) ppm. TOFMS: m/z calcd for C₃₅H₄₂O₆Na: 581.2874; found: 581.2903.

19

The authors quote [α]_D ²⁶ -131.8 (c 0.05, CHCl₃) for the natural (-)-denticulaflavonol.⁹ Compound 1 has a value of [α]_D ²² +15.0 (c 0.10, CHCl₃) and some derivatives have similar values and the same sign, for instance 16 [α]_D ²² +13.6 (c 0.14, CHCl₃), 17 [α]_D ²² +14.4 (c 0.09, CHCl₃), and 20 [α]_D ²² +12.0 (c 0.65, CHCl₃), so it can be concluded that 1 is the enantiomer of the natural (-)-denticulaflavonol. The difference in the values could be attributed to the small amount of the natural compound isolated.

20

Spectroscopic Data of Macarangin (2) IR (film): 3380, 2925, 1650, 1608, 1555, 1513, 1484, 1444, 1371, 1315, 1256, 1181, 1087, 1031 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 12.10 (1 H, s, 5-OH), 8.13 (2 H, d, J = 9.0 Hz, H-2′, H-6′), 6.97 (2 H, d, J = 9.0 Hz, H-3′, H-5′), 6.57 (1 H, s, 3-OH), 6.48 (1 H, s, H-8), 6.19 (1 H, s, 7-OH), 5.30 (1 H, t, J = 7.0 Hz, H-2′′), 5.11 (1 H, s, 4′-OH), 5.06 (1 H, m, H-7′′), 3.49 (2 H, d, J = 7.0 Hz, H-1′′), 2.10 (4 H, s, H-5′′, H-6′′), 1.84 (3 H, s, H-4′′), 1.68 (3 H, s, H-10′′), 1.60 (3 H, s, H-9′′) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.2 (C-4), 161.7 (C-7), 158.0 (C-5), 157.4 (C-4′), 155.0 (C-9), 145.5 (C-2), 140.0 (C-3′′), 132.2 (C-3), 132.1 (C-8′′), 129.6 (C-2′, C-6′), 123.6 (C-1′), 123.3 (C-7′′), 120.9 (C-2′′), 115.3 (C-3′, C-5′), 109.2 (C-6), 103.8 (C-10), 94.4 (C-8), 39.6 (C-5′′), 25.6 (C-10′′), 26.4 (C-6′′), 21.4 (C-1′′), 17.6 (C-9′′), 16.2 (C-4′′) ppm. TOFMS: m/z calcd for C₂₅H₂₆O₆Na: 445.1659; found: 445.1639.

21

Spectroscopic Data of Isomacarangin (3) IR (film): 3388, 2918, 1648, 1608, 1561, 1509, 1438, 1374, 1315, 1241, 1176, 1114 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 11.74 (1 H, s, 5-OH), 8.12 (2 H, d, J = 8.9 Hz, H-2′, H-6′), 6.98 (2 H, d, J = 8.9 Hz, H-3′, H-5′), 6.61 (1 H, s, 3-OH), 6.32 (1 H, s, H-6), 6.14 (1 H, s, 7-OH), 5.31 (1 H, t, J = 6.9 Hz, H-2′′), 5.08 (1 H, s, 4′-OH), 5.04 (1 H, m, H-7′′), 3.62 (2 H, d, J = 6.9 Hz, H-1′′), 2.09 (4 H, s, H-5′′, H-6′′), 1.85 (3 H, s, H-4′′), 1.65 (3 H, s, H-10′′), 1.57 (3 H, s, H-9′′) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 175.5 (C-4), 161.0 (C-7), 159.0 (C-5), 157.4 (C-4′), 153.8 (C-9), 145.4 (C-2), 139.4 (C-3′′), 132.2 (C-3), 132.1 (C-8′′), 129.9 (C-2′, C-6′), 123.6 (C-1′, C-7′′), 121.0 (C-2′′), 115.7 (C-3′, C-5′), 105.0 (C-8), 103.8 (C-10), 99.2 (C-6), 39.6 (C-5′′), 26.5 (C-6′′), 25.6 (C-10′′), 21.8 (C-1′′), 17.6 (C-9′′), 16.3 (C-4′′) ppm. TOFMS: m/z calcd for C₂₅H₂₅O₆: 421.1616; found: 421.1642.