M.V. Reddy et al. / European Journal of Medicinal Chemistry 45 (2010) 3125e3134
3131
nitrogen condition at 140 ꢁC for 7 h in dry DMF (10 mL) in the
presence of tetrakis(triphenylphosphine)palladium(0) complex
(0.05 mmol). The contents were cooled, diluted with hydrochloric
acid and extracted with diethyl ether (3 ꢀ 100 mL), organic layer
washed with water (2 ꢀ 50 mL) dried over anhydrous sodium
sulfate and concentrated under reduced pressure. The crude
product was purified by cc over silica gel (60:120 mesh) with ethyl
acetate/hexane (15:85) as eluent to afford 9 (0.81 g, 57%) as semi-
solid. Anal. Calcd for C25H30O2: C, 82.83; H, 8.344%. Found: C, 83.24;
H, 8.351%. 1H NMR (200 MHz, CDCl3): dH 1.33 (3H, s, eCeCH3), 1.63
(2H, m, ]CHCH2CH2e), 1.65 and 1.69 (3H each, s, ]C(CH3)2), 2.03
(2H, m, ]CHCH2CH2), 3.84 (3H, s, eOCH3), 5.13 (1H, t, J ¼ 6.9 Hz,
eCH2CH]C), 6.25 (2H, m, 2ꢀ AreCH]CHe), 6.81 (5H, m, 2ꢀ
AreCH]CHe, 3xAreH), 7.23 (4H, m, 2ꢀ AreH, 2ꢀ Ar0eH), 7.46 (1H,
d, J ¼ 8.4 Hz, Ar0eH). 13C NMR (50 MHz, CDCl3): dC 18.11, 23.83,
24.45, 26.13, 42.16, 44.22, 55.91, 111.33, 115.78, 121.06, 122.15,
125.37, 126.94, 127.85, 128.40, 132.1, 132.4, 136.7, 138.9, 156.1, 158.7.
MS Mþ ꢂ 1 at m/z 361. IR gmax (neat): 757, 925, 1040, 1064, 1233,
1.32 (3H, s, eCeCH3), 1.62 (2H, m, ]CHCH2CH2e), 1.64 and 1.71 (3H
each, s, ]C(CH3)2), 2.04 (2H, m, ]CHCH2CH2e), 3.83 (3H, s, eOCH3),
5.17 (1H, t, J ¼ 6.9 Hz, eCH2CH]C), 6.17 (2H, d, J ¼ 16.2 Hz, 2ꢀ
AreCH]CHe), 6.33 (2H, d, J ¼ 16.2 Hz, 2ꢀ AreCH]CHe), 6.80 (2H,
d, J ¼ 8.6 Hz, 2ꢀ AreH), 6.88 (2H, d, J ¼ 8.6 Hz, 2ꢀ Ar0eH), 7.29 (2H, d,
J ¼ 8.6 Hz, 2ꢀ AreH), 7.34 (2H, d, J ¼ 8.6 Hz, 2ꢀ Ar0eH). 13C NMR
(125 MHz, CDCl3): dC 16.73, 22.42, 23.10, 24.74, 40.83, 41.09, 54.37,
113.01, 114.46, 123.92, 125.61, 126.26, 126.44, 129.79, 129.81, 130.35,
135.08, 135.18, 153.85, 157.73. MS Mþ ꢂ 1 at m/z 361. IR gmax (neat):
817, 970, 1034, 1102, 1173, 1246, 1302, 1374, 1441, 1511, 1608, 2853,
25
2925, 2964, 3030, 3305 cmꢂ1
[a]
¼ þ2.9 (c 1.0, CHCl3). HPLC: Daicel
D
CHIRALCEL AD-H, mobile phase hexanes/isopropanol (98:2), detec-
tion wavelength ¼ 254 nm, flow rate ¼ 0.8 mL/min, Tr ¼ 25.59 min.
4.1.12. Preparation of 4-{3-(4-fluorostyryl)-3,7-dimethylocta-1,
6-dienyl}phenol (13)
Bakuchiol 1 (0.5 g, 1.95 mmol) was dissolved in DMF (2.5 mL,
0.2 M solution) and stirred at room temperature. To the clear
solution of the above mixture was added 4-fluorophenylboronic
acid (323 mg, 2.34 mmol, 1.2 equiv.) followed by a single addition of
Na2CO3 (413 mg, 3.9 mmol) and Pd(OAc)2 (0.19 mmol). The reaction
flask was fitted with an oxygen balloon, heated to 100 ꢁC, and
stirred for 7 h. The mixture was then diluted with diethyl ether
(20 mL), and washed with aqueous NaCl solution (2 ꢀ 25 mL). The
organic layer was dried over anhydrous Na2SO4 and filtered. The
filtrate was concentrated under reduced pressure and the crude
product purified by cc with hexaneeEtOAc (90:10) as the eluent
gave 13 (339 mg, 49% yield) as a semisolid. Anal. Calcd for
C24H27FO: C, 82.25; H, 7.764%. Found: C, 82.41; H, 7.744%. 1H NMR
(500 MHz, CDCl3): dH 1.30 (3H, s, eCeCH3), 1.58 (2H, m, ]
CHCH2CH2e), 1.59 and 1.68 (3H each, s, ]C(CH3)2), 2.00 (2H, m, ]
CHCH2CH2e), 5.13 (1H, t, J ¼ 6.9 Hz, eCH2CH]C), 6.13 and 6.18 (1H
each, d, J ¼ 16.2 Hz, 2ꢀ AreCH]CHe), 6.30 and 6.33 (1H each, d,
J ¼ 16.2 Hz, 2ꢀ AreCH]CHe), 6.78 (2H, d, J ¼ 8.4 Hz, 2ꢀ AreH),
6.99 (2H, d, J ¼ 8.6 Hz, 2ꢀ AreH), 7.26 (2H, d, J ¼ 8.4 Hz, 2ꢀ AreH),
7.33 (2H, d, J ¼ 8.6 Hz, 2ꢀ Ar0eH). 13C NMR (125 MHz, CDCl3): dC
18.40, 23.41, 24.07, 26.42, 42.41, 42.85,115.74,116.12,125.45,126.79,
127.46, 128.20, 131.41, 134.69, 136.39, 138.68, 155.51, 163.66. MS
1371, 1457, 1509, 1578, 1606, 2853, 2924, 2959, 3411 cmꢂ1
.
4.1.9. Preparation of (R)-4-{3-(4-methoxystyryl)-3,7-dimethylocta-
1,6-dienyl}phenol (10)
The title compound was prepared by the method described for
the preparation of compound 9 by coupling reaction of bakuchiol 1
(0.5 g, 1.95 mmol) with 4-iodoanisole (547 mg, 2.34 mmol) to give
10 (388 mg, 55% yield) as semisolid. Anal. Calcd for C25H30O2: C,
82.83; H, 8.344%. Found: C, 83.15; H, 8.353%. 1H NMR (200 MHz,
CDCl3): dH 1.28 (3H, s, eCeCH3), 1.57 (2H, m, ]CHCH2CH2e), 1.59
and 1.67 (3H each, s, ]C(CH3)2), 1.98 (2H, m, ]CHCH2CH2e), 3.79
(3H, s, eOCH3), 5.12 (1H, t, J ¼ 6.9 Hz, eCH2CH]), 6.11 (2H, d,
J ¼ 16.2 Hz, 2ꢀ AreCH]CHe), 6.30 (2H, d, J ¼ 16.2 Hz, 2ꢀ AreCH]
CHe), 6.76 (2H, d, J ¼ 8.5 Hz, 2ꢀ AreH,), 6.85 (2H, d, J ¼ 8.7 Hz, 2ꢀ
Ar0eH), 7.26 (2H, d, J ¼ 8.5 Hz, 2ꢀ AreH), 7.32 (2H, d, J ¼ 8.7 Hz, 2ꢀ
Ar0eH). 13C NMR (50 MHz, CDCl3): dC 18.10, 23.81, 24.50, 26.13,
42.22, 42.49, 55.75, 114.40, 115.83, 125.31, 127.0, 127.65, 127.84,
131.19, 131.21, 136.54, 155.1, 159.5. MS Mþ ꢂ 1 at m/z 361. IR gmax
(neat): 817, 970, 1035, 1098, 1246, 1439, 1511, 1608, 2854, 2925,
25
2963, 3030, 3159 cmꢂ1
[a
]
¼ ꢂ2.9 (c 1.0, CHCl3). HPLC: Daicel
D
CHIRALCEL AD-H, mobile phase hexane/isopropanol (98:2), UV
M
þ ꢂ 1 at m/z 349. IR gmax (neat): 757, 1018, 1123, 1157, 1216, 1403,
PDA ¼ 254 nm, flow rate ¼ 0.8 mL/min, Tr ¼ 22.35 min.
1456, 1508, 1602, 2850, 2920, 2960, 3405 cmꢂ1
.
4.1.10. Preparation of 4-{3-(4-hydroxystyryl)-3,7-dimethylocta-1,
6-dienyl} phenol (11)
4.1.13. Preparation of 4-{3-(4-aminostyryl)-3,7-dimethylocta-1,
6-dienyl}phenol (14)
The title compound was prepared by the method described for
The title compound was prepared by the method described for the
compound 9 by coupling reaction of bakuchiol (0.5 g, 1.95 mmol)
with 4-iodobenzenamine (512 mg, 2.34 mmol) to give 14 (331 mg,
49% yield) as semisolid. Anal. Calcd for C24H29NO: C, 82.95; H, 8.412;
N, 4.03%. Found: C, 83.42; H, 8.419; N, 4.14%. 1H NMR (200 MHz,
CDCl3): dH 1.25 (3H, s, eCeCH3),1.57 (2H, m, ]CHCH2CH2e),1.58 and
1.67 (3H each, s, ]C(CH3)2), 1.99 (2H, m, ]CHCH2CH2e), 5.13 (1H, t,
J ¼ 6.9 Hz, eCH2CH]C), 6.07 and 6.11 (1H each, d, J ¼ 16.2 Hz, 2ꢀ
AreCH]CHe), 6.25 and 6.27 (1H each, d, J ¼ 16.2 Hz, 2ꢀ AreCH]
CHe), 6.64 (2H, d, J ¼ 8.6 Hz, 2ꢀ AreH), 6.75 (2H, d, J ¼ 8.4 Hz, Ar0eH),
7.19 (2H, d, J ¼ 8.4 Hz, 2ꢀ AreH), 7.24(2H, d, J ¼ 8.6 Hz, 2ꢀ Ar0eH).13C
NMR (125 MHz, CDCl3): dC 17.68, 23.40, 24.15, 25.70, 41.85, 41.99,
115.48, 124.78, 124.96, 126.45, 126.53, 126.91, 127.20, 127.38, 129.75,
131.88,132.65,134.76,136.27, 146.1, 154.85. MS Mþ ꢂ 1 at m/z 346. IR
gmax (neat): 617, 655, 911, 972,1014,1110,1195,1369,1412,1452,1505,
the compound
9 by coupling reaction of bakuchiol (0.5 g,
1.95 mmol) with 4-iodophenol (514 mg, 2.34 mmol) to give 11
(325 mg, 48% yield) as semisolid. Anal. Calcd for C24H28O2: C, 82.72;
H, 8.101%. Found: C, 83.99; H, 8.110%. 1H NMR (200 MHz, CDCl3): dH
1.28 (3H, s, eC(CH]CH2)CH3), 1.57 (2H, m, ]CHCH2CH2e), 1.59 and
1.67 (3H each, s, ]C(CH3)2), 2.00 (2H, m, ]CHCH2CH2), 5.14 (1H, t,
J ¼ 6.9 Hz, eCH2CH]C), 6.11 (2H, d, J ¼ 16.2 Hz, 2ꢀ AreCH]CHe),
6.29 (2H, d, J ¼ 16.2 Hz, 2ꢀ AreCH]CH), 6.77 (4H, d, J ¼ 8.6 Hz, 4ꢀ
AreH), 7.26 (4H, d, J ¼ 8.6 Hz, 4ꢀ Ar0eH). 13C NMR (125 MHz,
CDCl3): dC 17.71, 23.39, 24.03, 25.74, 41.77, 42.06, 115.45, 124.87,
126.54, 127.43, 130.81, 131.40, 136.08, 154.7. MS Mþ ꢂ 1 at m/z 347.
IR gmax (neat): 757, 816, 970, 1015, 1101, 1171, 1234, 1375, 1446, 1511,
1609, 2854, 2925, 2961, 3022, 3363 cmꢂ1
.
4.1.11. Preparation of (S)-4-{3-(4-methoxystyryl)-3,7-dimethylocta-
1,6-dienyl} phenol (12)
1603, 1633, 2855, 2922, 2967, 3033 cmꢂ1
.
The title compound was prepared by the method described for
the compound 9 by coupling reaction of compound 3 (0.5 g,
1.85 mmol) with 4-iodophenol (488 mg, 2.22 mmol) to give 12
(388 mg, 58% yield) as semisolid. Anal. Calcd for C25H30O2: C, 82.83;
H, 8.344%. Found: C, 83.45; H, 8.339%. 1H NMR (500 MHz, CDCl3): dH
4.1.14. Preparation of 5-{3-(4-hydroxystyryl)-3,7-dimethylocta-1,
6-dienyl}-2-methoxybenzaldehyde (15)
The title compound was prepared by the method described for
the compound
9 by coupling reaction of bakuchiol (0.5 g,
1.95 mmol) with 5-bromo-2-methoxybenzaldehyde (500 mg,