F. Roelens et al. / European Journal of Medicinal Chemistry 40 (2005) 1042–1051
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for C20H22O5 342.1467; [M – H+] calcd 341.1389; found
341.1382. Anal. C20H22O5 (C, H).
C(3)–HA), 3.03 (dd, 1H, J = 15.8, 6.7 Hz, C(3)–HB), 4.36
(dd, 1H, J = 6.7, 1.8 Hz, C(4)–H), 6.27 (s, 1H, C(6)–H), 6.63
(d, 2H, J = 8.5 Hz, C(3′)–H and C(5′)–H), 6.85 (d, 2H,
J = 8.5 Hz, C(2′)–H and C(6′)–H), 9.21, 9.26 and 9.43 (3s,
1H each, C(4′)–OH, C(5)–OH and C(7)–OH); 13C NMR
(75 MHz, DMSO-d6) d 30.41 (3C), 33.65, 33.93, 35.78, 37.87,
99.18, 104.22, 108.46, 115.93 (2C), 128.35 (2C), 133.21,
152.05, 153.14, 155.67, 156.74, 168.76; HRMS calcd for
C20H22O5 342.1467; [M – H+] calcd 341.1389; found
341.1377. Anal. C20H22O5 (C, H).
5.1.4.3. ( )-8-n-Heptyl-5,7-dihydroxy-4-(4-hydroxyphenyl)-
3,4-dihydrocoumarin (5c). Hexane/EtOAc, 11:9.Yield: 76%.
1H NMR (300 MHz, DMSO-d6) d 0.85 (br t, 3H, J = 6.7 Hz,
C(7a)–H), 1.20–1.48 (m, 10H, C(2a)–H to C(6a)–H), 2.48
(br t, 2H, J = 7.0 Hz, C(1a)–H), 2.76 (dd, 1H, J = 15.8, 1.8 Hz,
C(3)–HA), 3.06 (dd, 1H, J = 15.8, 6.7 Hz, C(3)–HB), 4.34
(dd, 1H, J = 6.7, 1.8 Hz, C(4)–H), 6.24 (s, 1H, C(6)–H), 6.64
(d, 2H, J = 8.5 Hz, C(3′)–H and C(5′)–H), 6.84 (d, 2H,
J = 8.5 Hz, C(2′)–H and C(6′)–H), 9.27, 9.36, and 9.43 (3s,
1H each, C(4′)–OH, C(5)–OH, and C(7)–OH); 13C NMR
(75 MHz, DMSO-d6) d 14.69, 22.78, 22.88, 29.29, 29.57,
29.93, 32.05, 33.72, 37.87, 99.03, 104.13, 108.01, 115.86
(2C), 128.31 (2C), 133.24, 151.45, 152.91, 155.90, 156.67,
168.83; HRMS calcd for C22H26O5 370.1780; [M – H+] calcd
369.1702; found 369.1694. Anal. C22H26O5 (C, H).
5.1.4.7. ( )-8-(3-Methylbutyl)-5,7-dihydroxy-4-(4-hydroxy-
phenyl)-3,4-dihydrocoumarin (5g). Hexane/EtOAc, 1:1.Yield:
73%. 1H NMR (300 MHz, DMSO-d6) d 0.90 (d, 6H,
J = 6.7 Hz, C(4a)–H and C(5a)–H), 1.31 (br q, 2H, J = 6.8 Hz,
C(2a)–H), 1.50 (br n, 1H, J = 6.7 Hz, C(3a)–H), 2.51 (br t,
2H, J = 6.9 Hz, C(1a)–H), 2.76 (dd, 1H, J = 15.8, 1.8 Hz,
C(3)–HA), 3.06 (dd, 1H, J = 15.8, 6.7 Hz, C(3)–HB), 4.34
(dd, 1H, J = 6.7, 1.8 Hz, C(4)–H), 6.24 (s, 1H, C(6)–H), 6.64
(d, 2H, J = 8.5 Hz, C(3′)–H and C(5′)–H), 6.85 (d, 2H,
J = 8.5 Hz, C(2′)–H and C(6′)–H), 9.22, 9.30, and 9.37 (3s,
1H each, C(4′)–OH, C(5)–OH and C(7)–OH); 13C NMR
(75 MHz, DMSO-d6) d 20.98, 23.19, 23.25, 28.21, 33.71,
37.81, 39.31, 99.10, 104.25, 108.29, 115.89 (2C), 128.30 (2C),
133.24, 151.38, 152.88, 155.82, 156.64, 168.85; HRMS calcd
for C20H22O5 342.1467; [M – H+] calcd 341.1389; found
341.1383. Anal. C20H22O5 (C, H).
5.1.4.4. ( )-8-n-Undecyl-5,7-dihydroxy-4-(4-hydroxyphenyl)-
3,4-dihydrocoumarin (5d). Hexane/EtOAc, 3:2. Yield: 68%.
1H NMR (300 MHz, DMSO-d6) d 0.85 (br t, 3H, J = 6.5 Hz,
C(11a)–H), 1.19–1.43 (m, 18H, C(2a)–H to C(10a)–H), 2.48
(br t, 2H, J = 7.0 Hz, C(1a)–H), 2.75 (dd, 1H, J = 15.8, 1.8 Hz,
C(3)–HA), 3.05 (dd, 1H, J = 15.8, 6.7 Hz, C(3)–HB), 4.34
(dd, 1H, J = 6.7, 1.8 Hz, C(4)–H), 6.24 (s, 1H, C(6)–H), 6.63
(d, 2H, J = 8.5 Hz, C(3′)–H and C(5′)–H), 6.84 (d, 2H,
J = 8.5 Hz, C(2′)–H and C(6′)–H), 9.21, 9.30, and 9.37 (3s,
1H each, C(4′)–OH, C(5)–OH, and C(7)–OH); 13C NMR
(75 MHz, DMSO-d6) d 14.61, 22.76, 22.86, 29.38, 29.59,
29.69, 29.76, 31.96, 33.75, 37.83, 99.14, 104.22, 108.11,
115.89 (2C), 128.29 (2C), 133.26, 151.45, 152.92, 155.90,
156.68, 168.76; HRMS calcd for C26H34O5 426.2406; [M –
H+] calcd 425.2328; found 425.2319.Anal. C26H34O5 (C, H).
5.1.4.8. ( )-8-Benzyl-5,7-dihydroxy-4-(4-hydroxyphenyl)-3,4-
dihydrocoumarin (5h). Hexane/EtOAc, 1:1. Yield: 81%. 1H
NMR (300 MHz, DMSO-d6) d 2.77 (dd, 1H, J = 15.8, 1.8 Hz,
C(3)–HA), 3.07 (dd, 1H, J = 15.8, 6.7 Hz, C(3)–HB), 3.82 (d,
1H, J = 14.5 Hz, C(1a)–HA), 3.86 (d, 1H, J = 14.5 Hz, C(1a)–
HB), 4.37 (dd, 1H, J = 6.7, 1.8 Hz, C(4)–H), 6.30 (s, 1H, C(6)–
H), 6.64 (d, 2H, J = 8.5 Hz, C(3′)–H and C(5′)–H), 6.85 (d,
2H, J = 8.5 Hz, C(2′)–H and C(6′)–H), 7.09–7.26 (m, 5H,
C(3a)–H to C(7a)–H), 9.23, 9.45, and 9.49 (3s, 1H each,
C(4′)–OH, C(5)–OH, and C(7)–OH); 13C NMR (75 MHz,
DMSO-d6) d 28.63, 33.73, 37.79, 99.16, 104.38, 106.63,
115.91 (2C), 126.11, 128.29 (2C), 128.75 (4C), 133.13,
142.09, 151.47, 153.65, 156.04, 156.69, 168.69; HRMS calcd
for C22H18O5 362.1154; [M – H+] calcd 361.1076; found
361.1090. Anal. C22H18O5 (C, H).
5.1.4.5. ( )-8-(2-Methylpropyl)-5,7-dihydroxy-4-(4-hydroxy-
phenyl)-3,4-dihydrocoumarin (5e). Hexane/EtOAc, 1:1.Yield:
1
78%. H NMR (300 MHz, DMSO-d6) d 0.85 and 0.86 (2d,
3H each d, J = 6.7 Hz each d, C(3a)–H and C(4a)–H), 1.82
(br m, 1H, J = 6.8 Hz, C(2a)–H), 2.38 (d, 2H, J = 7.0 Hz,
C(1a)–H), 2.76 (dd, 1H, J = 15.8, 1.8 Hz, C(3)–HA), 3.04 (dd,
1H, J = 15.8, 6.7 Hz, C(3)–HB), 4.34 (dd, 1H, J = 6.7, 1.8 Hz,
C(4)–H), 6.26 (s, 1H, C(6)–H), 6.63 (d, 2H, J = 8.5 Hz,
C(3′)–H and C(5′)–H), 6.85 (d, 2H, J = 8.5 Hz, C(2′)–H and
C(6′)–H), 9.22, 9.29, and 9.40 (3s, 1H each, C(4′)–OH, C(5)–
OH, and C(7)–OH); 13C NMR (75 MHz, DMSO-d6) d 23.02,
23.05, 28.92, 31.90, 33.70, 37.86, 99.11, 104.15, 107.19,
115.89 (2C), 128.29 (2C), 133.22, 151.67, 153.02, 156.19,
156.68, 168.77; HRMS calcd for C19H20O5 328.1311; [M –
H+] calcd 327.1232; found 327.1226.Anal. C19H20O5 (C, H).
5.1.4.9. ( )-8-(2-Phenylethyl)-5,7-dihydroxy-4-(4-hydroxy-
phenyl)-3,4-dihydrocoumarin (5i). Hexane/EtOAc, 1:1.Yield:
1
77%. H NMR (300 MHz, DMSO-d6) d 2.66–2.83 (m, 5H,
C(3)–HA, C(1a)–H, and C(2a)–H), 2.93 (dd, 1H, J = 15.8,
6.7 Hz, C(3)–HB), 4.30 (dd, 1H, J = 6.7, 1.8 Hz, C(4)–H),
6.27 (s, 1H, C(6)–H), 6.63 (d, 2H, J = 8.5 Hz, C(3′)–H and
C(5′)–H), 6.79 (d, 2H, J = 8.5 Hz, C(2′)–H and C(6′)–H),
7.11–7.28 (m, 5H, C(4a)–H to C(8a)–H), 9.28, 9.47, and 9.50
(3s, 1H each, C(4′)–OH, C(5)–OH, and C(7)–OH); 13C NMR
(75 MHz, DMSO-d6) d 25.05, 33.79, 35.80, 37.75, 99.23,
104.33, 107.15, 115.89 (2C), 126.24, 128.31 (2C), 128.71
(2C), 128.97 (2C), 133.18, 142.66, 151.49, 153.17, 155.97,
5.1.4.6. ( )-8-(2,2-Dimethylpropyl)-5,7-dihydroxy-4-(4-
hydroxyphenyl)-3,4-dihydrocoumarin (5f). Hexane/EtOAc,
1:1. Yield: 80%. 1H NMR (300 MHz, DMSO-d6) d 0.88 (s,
9H, C(2a)-(CH3)3), 2.43 (d, 1H, J = 12.7 Hz, C(1a)–HA), 2.49
(d, 1H, J = 12.7 Hz, C(1a)–HB), 2.77 (dd, 1H, J = 15.8, 1.8 Hz,