CHEMMEDCHEM
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1169, 1136, 984, 917, 839, 824, 786, 688, 668 cmꢀ1
;
1H NMR
hydrous magnesium sulfate, filtered, and concentrated to dryness.
The crude residue was purified by flash column chromatography
(by using the indicated solvent) to give phenolic aza-goniothala-
min analogues 23–25.
(250 MHz, CDCl3): d=7.71 (d, J=15.6 Hz, 1H), 7.43 (d, J=15.6 Hz,
1H), 7.37–7.20 (m, 5H), 7.16–7.07 (m, 2H), 6.83 (d, J=8.2 Hz, 1H),
6.81–6.72 (m, 1H), 6.54 (d, J=15.9 Hz, 1H), 6.23 (dd, J=15.9,
5.8 Hz, 1H), 6.07 (dd, J=9.8, 2.5 Hz, 1H), 5.62 (t, J=5.6 Hz, 1H),
2.95–2.78 (m, 1H), 2.55 (dd, J=18.6, 6.1 Hz, 1H), 1.02 (s, 9H), 1.01
(s, 9H), 0.24 ppm (brs, 12H); 13C NMR (62.9 MHz, CDCl3): d=168.5
(C0), 165.2 (C0), 149.1 (C0), 147.0 (C0), 144.0 (CH), 142.3 (CH), 136.1
(C0), 131.9 (CH), 128.7 (C0), 128.4 (2CH), 127.7 (CH), 126.8 (CH),
126.4 (2CH), 125.9 (CH), 122.0 (CH), 121.1 (CH), 121.1 (CH), 119.5
(CH), 52.7 (CH), 29.8 (CH2), 25.9 (3CH3), 25.8 (3CH3), 18.4 (C0),
18.4 (C0), ꢀ4.2 ppm (4CH3); HRMS (ESI+): m/z calcd for
C34H48NO4Si2 [M+H+]: 590.3122; found: 590.3173.
1-((E)-3-(3,4-Dihydroxyphenyl)acryloyl)-6-styryl-5,6-dihydropyri-
din-2(1H)-one (23): Prepared according to the general procedure
for the deprotection reaction by using hydrogen fluoride pyridine
complex in 83% yield (yellow solid). Eluent: hexanes/ethyl acetate,
1:2 v/v; mp: 178.0–180.08C; IR (thin film): n˜ =3330, 1675, 1660,
1590, 1529, 1391, 1367, 1304, 1278, 1201, 1184, 1144, 1109, 1045,
966, 820, 742, 690 cmꢀ1 1H NMR (250 MHz, [D6]acetone): d=8.28
;
(brs, 1H), 7.60 (d, J=15.6 Hz, 1H), 7.46–7.35 (m, 3H), 7.34–7.19 (m,
3H), 7.17 (d, J=1.8 Hz, 1H), 7.03 (dd, J=8.2, 1.8 Hz, 1H), 6.98–6.85
(m, 2H), 6.50 (d, J=16.0 Hz, 1H), 6.37 (dd, J=16.0, 5.0 Hz, 1H),
5.99 (dd, J=9.7, 2.7 Hz, 1H), 5.55 (t, J=5.0 Hz, 1H), 3.09–2.87 (m,
2H), 2.69 ppm (dd, J=18.7, 6.1 Hz, 1H); 13C NMR (62.9 MHz,
[D6]acetone): d=168.9 (C0), 166.2 (C0), 148.6 (C0), 146.3 (C0), 144.4
(CH), 144.1 (CH), 137.5 (C0), 131.9 (CH), 129.5 (2CH), 129.2 (CH),
128.6 (CH), 127.3 (2CH), 126.2 (CH), 122.7 (CH), 120.2 (CH), 116.5
(CH), 115.1 (CH), 53.7 (CH), 30.4 ppm (CH2); HRMS (ESI+): m/z calcd
for C22H20NO4 [M+H+]: 362.1392; found: 362.1457.
(E)-1-(3-(3,4-Bis(tert-butyldimethylsilyloxy)phenyl)propanoyl)-6-
styryl-5,6-dihydropyridin-2(1H)-one (21): Prepared according to
the general procedure for the N-acylation by using mixed anhy-
dride and LHMDS in 76% yield (white solid). Eluent: hexanes/ethyl
acetate, 3:1 v/v; mp: 91.5–93.08C; IR (thin film): n˜ =2956, 2929,
2893, 2885, 2856, 1693, 1511, 1390, 1286, 1252, 1187, 1137, 976,
907, 839, 824, 781, 751, 695 cmꢀ1 1H NMR (250 MHz, CDCl3): d=
;
7.37–7.20 (m, 5H), 6.80–6.67 (m, 4H), 6.50 (d, J=15.8 Hz, 1H), 6.19
(dd, J=15.8, 6.2 Hz, 1H), 6.03 (dd, J=9.8, 2.5 Hz, 1H), 5.60 (t, J=
5.8 Hz, 1H), 3.45–3.29 (m, 1H), 3.27–3.10 (m, 1H), 3.04–2.70 (m,
3H), 2.50 (dd, J=18.6, 6.1 Hz, 1H), 1.01 (s, 18H), 0.22 (s, 6H),
0.21 ppm (s, 6H); 13C NMR (62.9 MHz, CDCl3): d=175.1 (C0), 164.7
(C0), 146.4 (C0), 144.8 (C0), 142.1 (CH), 136.0 (C0), 134.1 (C0), 132.0
(CH), 128.4 (2CH), 127.8 (CH), 126.6 (CH), 126.4 (2CH), 125.8
(CH), 121.3 (CH), 121.2 (CH), 120.7 (CH), 52.1 (CH), 41.0 (CH2), 30.3
(CH2), 29.6 (CH2), 25.9 (6CH3), 18.3 (2C0), ꢀ4.2 (2CH3),
ꢀ4.2 ppm (2CH3); HRMS (ESI+): m/z calcd for C34H50NO4Si2 [M+
H+]: 592.3278; found: 592.3361.
(E)-1-(3-(3,4-Dihydroxyphenyl)propanoyl)-6-styryl-5,6-dihydro-
pyridin-2(1H)-one (24): Prepared according to the general proce-
dure for the deprotection reaction by using hydrogen fluoride pyri-
dine complex in 80% yield (white solid). Eluent: hexanes/ethyl ace-
tate, 1:2 v/v; mp: 156.0–158.08C; IR (thin film): n˜ =3500, 3190,
1704, 1669, 1623, 1523, 1401, 1252, 1184, 1150, 1115, 827, 813, 739,
688 cmꢀ1 1H NMR (250 MHz, [D6]acetone): d=7.66 (s, 1H), 7.42–
;
7.15 (m, 5H), 6.94–6.81 (m, 1H), 6.79–6.66 (m, 2H), 6.58 (dd, J=7.5,
2.5 Hz, 1H), 6.45 (d, J=16.0 Hz, 1H), 6.32 (dd, J=16.0, 5.0 Hz, 1H),
5.94 (dd, J=10.0, 2.5 Hz, 1H), 5.55 (t, J=5.0 Hz, 1H), 3.36–3.03 (m,
2H), 2.97–2.76 (m, 3H), 2.63 ppm (dd, J=20.0, 5.0 Hz, 1H); 13C NMR
(62.9 MHz, [D6]acetone): d=175.6 (C0), 165.7 (C0), 145.8 (C0), 144.2
(CH), 137.5 (C0), 134.0 (C0), 131.9 (CH), 129.5 (2CH), 129.0 (CH),
128.6 (CH), 127.3 (2CH), 126.2 (CH), 120.6 (CH), 116.4 (CH), 116.1
(CH), 53.1 (CH), 42.0 (CH2), 31.4 (CH2), 29.3 ppm (CH2); HRMS
(ESI+): m/z calcd for C22H22NO4 [M+H+]: 364.1549; found:
364.1566.
1-((E)-3-(4-(tert-Butyldimethylsilyloxy)-3-methoxyphenyl)acrylo-
yl)-6-styryl-5,6-dihydropyridin-2(1H)-one (22): Prepared accord-
ing to the general procedure for the N-acylation by using mixed
anhydride and LHMDS in 77% yield (yellow solid). Eluent: hexanes/
ethyl acetate, 3:1 v/v; mp: 145.0–147.08C; IR (thin film): n˜ =2953,
2934, 2893, 2860, 1686, 1508, 1396, 1339, 1285, 1256, 1198, 1162,
1036, 964, 918, 904, 840, 825, 781, 754, 696 cmꢀ1 1H NMR
;
(250 MHz, CDCl3): d=7.74 (d, J=15.5 Hz, 1H), 7.44 (d, J=15.5 Hz,
1H), 7.37–7.18 (m, 5H), 7.14–7.04 (m, 2H), 6.84 (d, J=8.6 Hz, 1H),
6.81–6.74 (m, 1H), 6.54 (d, J=16.0 Hz, 1H), 6.23 (dd, J=16.0,
5.8 Hz, 1H), 6.08 (dd, J=9.8, 2.7 Hz, 1H), 5.61 (t, J=5.7 Hz, 1H),
3.84 (s, 3H), 2.98–2.81 (m, 1H), 2.55 (dd, J=19.1, 6.5 Hz, 1H), 1.00
(s, 9H), 0.17 ppm (s, 6H); 13C NMR (62.9 MHz, CDCl3): d=168.5 (C0),
165.4 (C0), 151.1 (C0), 147.4 (C0), 144.4 (CH), 142.4 (CH), 136.1 (C0),
132.0 (CH), 129.0 (C0), 128.5 (2CH), 127.8 (CH), 126.9 (CH), 126.5
(2CH), 126.0 (CH), 122.6 (CH), 121.0 (CH), 119.5 (CH), 111.1 (CH),
55.4 (OCH3), 52.8 (CH), 29.9 (CH2), 25.6 (3CH3), 18.4 (C0),
ꢀ4.6 ppm (2CH3); HRMS (ESI+): m/z calcd for C29H36NO4Si [M+
H+]: 490.2414; found: 490.2460.
1-((E)-3-(4-Hydroxy-3-methoxyphenyl)acryloyl)-6-styryl-5,6-dihy-
dropyridin-2(1H)-one (25): Prepared according to the general pro-
cedure for the deprotection reaction by using hydrogen fluoride
pyridine complex in 94% yield (yellow solid). Eluent: hexanes/ethyl
acetate, 1:2 v/v; mp: 144.0–146.08C; IR (thin film): n˜ =3303, 1668,
1615, 1592, 1514, 1429, 1407, 1292, 1270, 1205, 1145, 1125, 1030,
1
999, 962, 826, 818, 741 cmꢀ1; H NMR (250 MHz, CDCl3): 7.74 (d, J=
15.0 Hz, 1H), 7.44 (d, J=15.0 Hz, 1H), 7.37–7.19 (m, 5H), 7.16–7.06
(m, 2H), 6.91 (d, J=7.5 Hz, 1H), 6.86–6.74 (m,1H), 6.54 (d, J=
16.0 Hz, 1H), 6.24 (dd, J=16.0, 7.5 Hz, 1H), 6.14–5.99 (m, 2H), 5.61
(t, J=7.5 Hz, 1H), 3.91 (s, 3H), 2.97–2.82 (m, 1H), 2.57 ppm (dd, J=
17.5, 7.5 Hz, 1H); 13C NMR (62.9 MHz, CDCl3): d=168.5 (C0), 165.5
(C0), 147.9 (C0), 146.7 (C0), 144.4 (CH), 142.5 (CH), 136.1 (C0), 132.0
(CH), 128.5 (2CH), 127.8 (CH), 127.7 (C0), 126.9 (CH), 126.5 (2
CH), 125.9 (CH), 123.5 (CH), 119.1 (CH), 114.6 (CH), 109.6 (CH), 55.9
(OCH3), 52.8 (CH), 29.9 ppm (CH2); HRMS (ESI+): m/z calcd for
C23H22NO4 [M+H+]: 376.1549; found: 376.1606.
General procedure for the deprotection by using HF·pyridine:
For the deprotection of the intermediates 20–22 containing a TBS
group, a freshly prepared solution of HF·pyridine in anhydrous pyr-
idine/anhydrous THF (27.0 mL of THF, 6.8 mL of pyridine, and
3.2 mL of HF·pyridine, 70:30) was added to a solution of the TBS-
protected lactams (0.5 mmol) in anhydrous THF (3.0 mL), at 08C
and under a nitrogen atmosphere. The resulting solution was
maintained with magnetic stirring for 2 h, and after this period,
a saturated aqueous solution of sodium hydrogen carbonate was
added until pHꢂ6 was reached (150 mL). The reaction mixture
was extracted with ethyl acetate (370 mL), and the organic layer
was washed with water (40 mL) and brine (40 mL), dried over an-
Biological assays
In vitro assays
Cell lines: Human tumor U251 (glioma), MCF-7 (breast), NCI-H460
(lung, non-small cells), HT-29 (colon), PC-3 (prostate), 786–0
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