Molecules 2019, 24, 2636
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starting aldehyde is 93%. This triallyl derivative 6h, pure at TLC, was not fully characterized, but
directly converted into 7h, following the same procedure described for 7c. Chromatography (PE/EtOAc
40:60) gave pure 7h (560 mg, 96%). White foam. Rf 0.51 (PE/EtOAc 50:50). IR: υmax 3297, 3064, 2938,
1759, 1677, 1648, 1601, 1506, 1451, 1418, 1367, 1299, 1257, 1189, 1155, 1121, 1081, 1014, 976, 956, 907, 829,
1
793, 731, 696, 635 cm−1. H-NMR (CDCl3):
δ 7.70 (d, J = 15.3 Hz, 1 H, CH=CHCO), 7.42 (d, J = 8.4 Hz,
2 H), 7.31 (t, J = 7.7 Hz, 1 H), 7.25–6.94 (m, 12 H), 6.84 (s, 1 H), 6.64 (d, J = 15.3 Hz, 1 H, CH=CHCO),
6.33 (broad t, J = 5.7 Hz, 1 H, NH), 6.08 (s, 1 H, CHN), 4.89, 4.65 (AB syst., J = 17.8 Hz, 2 H, CH2Ph),
4.51, 4.46 (AB part of an ABX syst, JAB = 14.6, JAX = 5.0, JBX = 6.0 Hz, CH2NH), 3.76 (s, 3 H, OCH3),
2.29 (s, 3 H, CH3CO), 2.27 (s, 3 H, CH3CO), 2.26 (s, 3 H, CH3CO). 13C-NMR (CDCl3):
δ
169.5, 169.4,
169.1, 168.8, 168.0 (C=O), 151.1, 150.8, 141.0, 139.7, 137.8, 134.0, 132.2 (quat.), 143.2 (CH=CHCO), 131.0
2), 129.6, 128.6 ( 2), 127.1, 126.2 ( 2), 125.1, 123.0, 121.9 ( 2), 120.84, 120.81, 120.6, 111.3 (aromatic
(×
×
×
×
CH), 118.3 (CH=CHCO), 62.3 (CHN), 55.8 (OCH3), 50.0 (CH2Ph), 43.2 (CH2NH), 21.1 (CH3CO), 21.0
(CH3CO), 20.6 (CH3CO). HRMS: m/z (ESI+): 665.2522 (M + H+). C38H37N2O9 requires 665.2499.
(R,S)-(E)-N-Benzyl-N-(2-(3-(hydroxy)benzyl)-1-(4-hydroxyphenyl)-2-oxoethyl)-3-(4-hydroxy-3-methoxyphenyl)
acrylamide (8h). Prepared from acetate 7h (100.0 mg, 150 µmol) following the same procedure used
for 8c. Yield: 76.2 mg (94%). The purity by HPLC (for conditions see the general remarks) was 94%.
Rf 0.32 (PE/EtOAc 60:40). 1H-NMR (DMSO-d6, 90 ◦C) (some signals were still rather broad at this
temperature):
δ 9.09 (s, 1 H), 8.90 (s, 2 H), 8.27 (broad s, 1 H), 7.41 (d, J = 15.3 Hz, 1 H, CH=CHCO),
7.25–7.02 (m, 9 H), 6.96 (s, 1 H), 6.90 (d, J = 8.1 Hz, 1 H), 6.75 (d, J = 8.1 Hz, 1 H), 6.72–6.61 (m, 5 H),
6.14 (broad s, CHN), 4.88 (d, J = 17.1 Hz, 1 H, CHHPh), 4.61 (d, J = 17.1 Hz, 1 H, CHHPh), 4.26, 4.21
(AB part of an ABX syst, JAB = 15.2, JAX = 5.9, JBX = 6.2 Hz, CH2NH), 3.76 (s, 3 H, OCH3).
N-Benzyl-N-(2-(tert-butylamino)-2-oxo-1-phenylethyl)cinnamamide (
benzylamine (180 L, 1.65 mmol), cinnamic acid (245 mg, 1.65 mmol) and tert-butyl isocyanide (185
1.65 mmol) were reacted as described for the synthesis of 6c. Chromatography (PE: AcOEt 75:25)
gave pure as a white foam (571 mg, 89%). Rf 0.36 (PE/EtOAc 75:25). IR: 3316, 3063, 3030,
9
). Benzaldehyde (153
µL, 1.50 mmol),
µ
µL,
9
υ
max
2971, 2926, 1650, 1596, 1547, 1496, 1470, 1450, 1411, 1392, 1363, 1351, 1331, 1303, 1284, 1253, 1220,
1201, 1189, 1174, 1078, 1032, 997, 976, 947, 915, 892, 860, 841, 804, 768, 758, 740, 723, 695, 642, 622,
1
615 cm−1. H-NMR (CDCl3):
δ 7.77 (d, J = 15.3 Hz, 1 H, CH=CHCO), 7.43–7.08 (m, 14 H), 7.01 (broad d,
J = 6.9 Hz, 1 H), 6.72 (d, J = 15.3 Hz, 1 H, PhCH=CH), 6.11 (s, 1 H, CHN), 5.68 (s, 1 H, NH), 4.93, 4.69
(AB syst., J = 17.9 Hz, 2 H, CH2Ph), 1.35 (s, 9 H, C(CH3)3). 13C-NMR (CDCl3):
168.9, 168.2 (C=O),
138.2, 135.3, 135.1 (quat.), 143.7 (CH=CHCO), 129.7 ( 3), 128.7 ( 2), 128.6 ( 2), 128.3 ( 3), 127.9, 126.9
2), 126.2 ( 2) (aromatic CH), 118.2 (CH=CHCO), 62.9 (CHN), 51.7 (C(CH3)3), 49.7 (CH2Ph), 28.6
(C(CH3)3). HRMS: m/z (ESI+): 427.2378 (M + H+). C28H31N2O2 requires 427.2386.
δ
×
×
×
×
(×
×
(E )-N-(1-(4-Acetoxyphenyl)-2-(tert-butylamino)-2-oxoethyl))-3-(4-acetoxy-3-methoxyphenyl)-N-((S)-1-
phenylethyl)acrylamide (12a) and (E)-N-(1-(4-Acetoxyphenyl)-2-(tert-butylamino)-2-oxoethyl))-3-(4-acetoxy-3-
methoxyphenyl)-N-((S)-1-phenylethyl)acrylamide (12b). Aldehyde (243 mg, 1.50 mmol), protected ferulic
L, 1.65 mmol) and tert-butyl isocyanide
L, 1.65 mmol) were reacted as described for the synthesis of 6c. Chromatography (PE/EtOAc
3
acid
(185
5
µ
(387 mg, 1.65 mmol), (S)-α-methylbenzylamine (212.7 µ
70:30) gave: the faster running diastereomer 11a (182.1 mg) (Rf = 0.27, PE/EtOAc 70:30), the slower
running diastereomer 11b (190.4 mg) (Rf = 0.19, PE/EtOAct 70:30), and some mixed fractions (37.6 mg).
A second chromatography of the mixed fractions gave additional 11a (21.7 mg) and 11b (15.9 mg).
Overall yield: 420.1 mg (44%). Diastereomeric ratio = 50:50. The realtive configuration was not
established. Diallyl derivatives 11a and 11b, pure at TLC, were not fully characterized, but directly
independently converted into 12a and 12b, following the same procedure described for 7c.
12a. Obtained in 45% yield (96.3 mg from 212.1 mg of 11a) after chromatography with PE/EtOAc 60:40).
Rf 0.34 (PE/EtOAc 60:40). IR:
υ
3300, 2965, 2930, 1768, 1689, 1644, 1603, 1547, 1508, 1452, 1434, 1416,
max
1389, 1368, 1337, 1260, 1193, 1152, 1123, 1034, 1014, 978, 946, 909, 883, 846, 828, 794 cm−1. H-NMR
1
(CDCl3) (due to the presence of conformers around the tertiary amide, the signals are rather broad