12
S. Dei et al. / Bioorganic & Medicinal Chemistry xxx (2017) xxx–xxx
eluent: CH2Cl2/MeOH 95:5. Yield 18%. 1H NMR (CD3OD) d: 7.85 (d,
J = 8.4 Hz, 2H, CH arom.); 7.57 (d, J = 16.0 Hz, 1H, CH@CH); 6.92 (d,
J = 8.4 Hz, 2H, CH arom.); 6.88 (s, 2H, CH arom.); 6.64 (d, J = 2.0 Hz,
1H, CH arom.); 6.62 (s, 1H, CHCO); 6.43 (d, J = 16.0 Hz, 1H,
CH@CH); 6.34 (d, J = 2.0 Hz, 1H, CH arom.); 4.87 (s, 2H, OCH2CO);
4.26 (t, J = 6.4 Hz, 2H, CH2O); 4.21 (t, J = 6.4 Hz, 2H, CH2O); 3.84
(s, 6H, OCH3); 3.79 (s, 3H, OCH3); 2.99–2.91 (m, 4H, NCH2); 2.72
(s, 3H, NCH3); 1.78–1.68 (m, 12H, CH2) ppm.
4H, CH2); 1.41–1.29 (m, 4H, CH2) ppm. 13C NMR (CDCl3) d:
178.30 (C); 168.34 (C); 167.01 (C); 163.06 (C); 160.51 (C); 156.18
(C); 153.44 (C); 144.61 (CH@CH); 140.13 (C); 133.64 (CH);
129.92 (C); 128.79 (CH); 128.16 (CH); 128.06 (CH); 125.68 (CH);
125.15 (CH); 123.94 (C); 117.97 (CH); 117.44 (CH@CH); 115.09
(CH); 106.50 (CH); 105.26 (CH); 65.59 (CH2O); 65.24 (CH2O);
64.57 (CH2O); 60.96 (OCH3); 58.61 (NCH2Ph); 56.16 (OCH3);
53.62 (CH2N); 53.52 (CH2N); 28.63 (CH2); 28.38 (CH2); 26.66
(2CH2); 23.77 (CH2); 23.57 (CH2) ppm.
Oxalate: mp 165–166 °C. Anal: C42H49NO16 (C, H, N).
Hydrochloride: mp 58–60 °C. Anal: C46H52ClNO10 (C, H, N).
4.1.16.11. 2-{2-[(2-{2-[(E)-5,7-Dihydroxy-4-oxo-4H-chromene-2-car-
bonyloxy] ethoxy}ethyl)(methyl)amino]ethoxy}ethyl (2E)-3-(3,4,5-tri-
methoxyphenyl)prop-2-enoate 11. Free base: chromatographic
eluent: CH2Cl2/petroleum ether/abs.EtOH/NH4OH 340:60:65:8.
Yield 79%. 1H NMR (CDCl3) d: 7.53 (d, J = 16.0 Hz, 1H, CH@CH);
6.71 (s, 1H, CHCO); 6.69 (s, 2H, CH arom.); 6.29 (d, J = 16.0 Hz,
1H, CH@CH); 6.28 (d, J = 2.0 Hz, 1H, CH arom.); 6.20 (d, J = 2.0 Hz,
1H, CH arom.); 4.38 (t, J = 6.4 Hz, 2H, CH2O); 4.28 (t, J = 6.4 Hz,
2H, CH2O); 3.85 (s, 9H, OCH3); 3.78–3.70 (m, 2H, OCH2); 3.69–
3.61 (m, 6H, OCH2); 2.83–2.75 (m, 4H, NCH2); 2.42 (s, 3H, NCH3)
ppm. 13C NMR (CDCl3) d: 181.54 (C); 166.89 (C); 166.06 (C);
162.06 (C); 159.78 (C); 157.52 (C); 153.37 (C); 151.27 (C); 145.17
(CH@CH); 140.07 (C); 129.77 (C); 116.86 (CH@CH); 113.48 (CH);
105.50 (C); 105.29 (CH); 100.63 (CH); 95.18 (CH); 69.07 (CH2O);
68.91 (CH2O); 68.45 (CH2O); 68.32 (CH2O); 68.22 (CH2O); 68.06
(CH2O); 65.76 (CH2O); 63.64 (CH2O); 56.94 (NCH2); 56.78
(NCH2); 56.20 (OCH3); 56.06 (OCH3); 42.50 (NCH3) ppm.
4.1.16.14. 2-{2-[Methyl-({2-[2-({2-[4-(4-oxo-4H-chromen-2-yl)phe-
noxy]acetyl}oxyethoxy]ethyl})amino]ethoxy}ethyl (2E)-3-(3,4,5-tri-
methoxyphenyl)prop-2-enoate 15. Free base: chromatographic
eluent: CH2Cl2/MeOH/NH4OH 93:7:0.3 Yield 6.2%. 1H NMR (CDCl3)
d: 8.21 (d, J = 7.6 Hz, 1H, CH arom.); 7.88 (d, J = 8.8 Hz, 2H, CH
arom.); 7.68 (t, J = 7.6 Hz, 1H, CH arom.); 7.62–7.53 (m, 2H, CH
arom. and CH@CH); 7.41 (t, J = 7.6 Hz, 1H, CH arom.); 7.03 (d, J =
8.8 Hz, 2H, CH arom.); 6.75 (s, 2H, CH arom.); 6.74 (s, 1H, CHCO);
6.37 (d, J = 16.0 Hz, 1H, CH@CH); 4.76 (s, 2H, OCH2CO); 4.39–4.34
(m, 4H, 2CH2OCO); 3.88 (s, 9H, OCH3); 3.74–3.49 (m, 8H, CH2O);
2.72–2.64 (m, 4H, CH2N); 2.36 (s, 3H, NCH3) ppm. ESI-MS:
[MÀH]+ species at m/z 706.
Hydrochloride: low melting solid. Anal: C38H44ClNO12 (C, H, N).
4.1.16.15.
2-{2-[Benzyl({2-[2-({2-[4-(4-oxo-4H-chromen-2-yl)phe-
Oxalate: mp 53–56 °C. Anal: C33H39NO17 (C, H, N).
noxy]acetyl}oxy)ethoxy]ethyl})amino]ethoxy}ethyl (2E)-3-(3,4,5-tri-
methoxyphenyl)prop-2-enoate 16. Free base: chromatographic
eluent: CH2Cl2/MeOH/NH4OH 95:5:0.5. Yield 73.0%. 1H NMR
(CDCl3) d: 8.20 (d, J = 8.0 Hz, 1H, CH arom.); 7.87 (d, J = 8.8 Hz,
2H, CH arom.); 7.66 (t, J = 8.0 Hz, 1H, CH arom.); 7.59 (d, J = 16.0 Hz,
1H, CH@CH); 7.53 (d, J = 8.0 Hz, 1H, CH arom.); 7.39 (t, J = 8.0 Hz,
1H, CH arom.); 7.35–7.20 (m, 5H, CH arom.); 7.00 (d, J = 8.8 Hz,
2H, CH arom.); 6.73 (s, 1H, CHCO); 6.72 (s, 2H, CH arom.); 6.36 (d, J
= 16.0 Hz, 1H, CH@CH); 4.69 (s, 2H, OCH2CO); 4.35–4.31 (m, 4H,
CH2OCO); 3.87 (s, 6H, OCH3); 3.85 (s, 3H, OCH3); 3.71–3.64 (m, 4H,
OCH2); 3.62 (s, 2H, NCH2Ph); 3.60–3.55 (m, 4H, OCH2); 2.79–2.73
(m, 4H, CH2N) ppm. 13C NMR (CDCl3) d: 178.33 (C); 168.24 (C);
166.85 (C); 163.06 (C); 160.43 (C); 156.19 (C); 153.43 (C); 145.09
(CH@CH); 133.64 (CH); 129.81 (C); 128.24 (CH); 128.07 (CH);
125.69 (CH); 125.15 (CH); 123.94 (C); 117.97 (CH); 117.04 (CH@CH);
115.11 (CH); 106.53 (CH); 105.31 (CH); 69.00 (OCH2); 68.54 (OCH2);
65.11 (OCH2); 64.44 (OCH2); 63.59 (OCH2); 60.96 (OCH3); 59.74
(NCH2Ph); 56.16 (OCH3); 53.83 (CH2N) ppm.
4.1.16.12.
5-{Methyl-[5-({2-[4-(4-oxo-4H-chromen-2-yl)phenoxy]
acetyl}oxy) pentyl]amino}pentyl (2E)-3-(3,4,5-trimethoxyphenyl)
prop-2-enoate 12. Free base: chromatographic eluent: CH2Cl2/
diethyl
ether/petroleum
ether/abs.EtOH/NH4OH
120:120:300:60:3.3. Yield 78.5%. 1H NMR (CDCl3) d: 8.17 (d, J =
8.0 Hz, 1H, CH arom.), 7.84 (d, J = 9.2 Hz, 2H, CH arom.); 7.64 (t, J =
8.0 Hz, 1H, CH arom.); 7.55 (d, J = 16.0 Hz, 1H, CH@CH); 7.49 (d,
J = 8.0 Hz, 1H, CH arom.); 7.36 (t, J = 8.0 Hz, 1H, CH arom.); 6.98
(d, J = 9.2 Hz, 2H, CH arom.); 6.71 (s, 2H, CH arom.); 6.69 (s, 1H,
CHCO); 6.31 (d, J = 16.0 Hz, 1H, CH@CH); 4.67 (s, 2H, OCH2CO);
4.20–4.16 (m, 4H, CH2OCO); 3.84 (s, 9H, OCH3); 2.31–2.26 (m,
4H, CH2N); 2.17 (s, 3H, NCH3); 1.70–1.63 (m, 4H, CH2); 1.52–1.25
(m, 8H, CH2); ppm. 13C NMR (CDCl3) d: 178.23 (C); 168.33 (C);
166.97 (C); 163.01 (C); 160.48 (C); 156.13 (C); 153.40 (C); 144.58
(CH@CH); 133.62 (CH); 129.90 (C); 128.02 (CH); 125.62 (CH);
125.12 (CH); 125.04 (C); 123.89 (C); 117.95 (CH); 117.42 (CH@CH);
115.06 (CH); 106.43 (CH); 105.22 (CH); 65.52 (CH2O); 65.21
(CH2O); 64.50 (CH2O); 60.92 (OCH3); 57.62 (CH2N); 57.53
(CH2N); 56.13 (OCH3); 56.10 (OCH3); 42.13 (NCH3); 28.68 (CH2);
28.45 (CH2); 26.87 (CH2); 26.82 (CH2); 23.93 (CH2); 23.75 (CH2)
ppm.
Hydrochloride: low melting solid. Anal: C44H48ClNO12 (C, H, N).
4.1.17. 5-{[(tert-Butoxy)carbonyl](5-hydroxypentyl)amino}pentyl
(2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate 44
To a solution of 4232 (278 mg, 0.68 mmol) in 10 mL of THF stir-
red at 0 °C, a solution of 185 mg of di-tert-butyl dicarbonate (0.85
mmol) in 5 mL of THF and triethylamine (0.19 mL, 1.36 mmol)
were added, and the mixture was stirred 30 min in ice-bath and
18 h at room temperature. The solution was concentrated in vacuo
and the oily residue was dissolved in CH2Cl2; the organic solution
was washed twice with water, dried on Na2SO4, and evaporated
yielding 275 mg (yield: 79.5%) of title compound as a yellow oil
that was not further purified. 1H NMR (CDCl3) d: 7.58 (d, J = 15.8
Hz, 1H, CH@CH); 6.75 (s, 2H, CH arom.); 6.33 (d, J = 15.8 Hz, 1H,
CH@CH); 4.19 (t, J = 6.4 Hz, 2H, CH2OCO); 3.89 (s, 6H, OCH3);
3.87 (s, 3H, OCH3); 3.64–3.61 (m, 2H, CH2OH); 3.20–3.14 (m, 4H,
CH2N); 1.74–1.69 (m, 4H, CH2); 1.45 (s, 9H, t-butyl); 1.74–1.32
(m, 8H, CH2) ppm.
Hydrochloride: mp 105–107 °C. Anal: C40H48ClNO10 (C, H, N).
4.1.16.13.
5-{Benzyl[5-({2-[4-(4-oxo-4H-chromen-2-yl)phenoxy]
acetyl}oxy)pentyl] amino}pentyl (2E)-3-(3,4,5-trimethoxyphenyl)
prop-2-enoate 13. Free base: chromatographic eluent: CH2Cl2/
MeOH/NH4OH 95:5:0.5. Yield 50.8%. 1H NMR (CDCl3) d: 8.20 (d, J
= 7.6 Hz, 1H, CH arom.); 7.87 (d, J = 8.8 Hz, 2H, CH arom.); 7.66
(t, J = 7.6 Hz, 1H, CH arom.); 7.58 (d, J = 16.0 Hz, 1H, CH@CH);
7.52 (d, J = 7.6 Hz, 1H, CH arom.); 7.39 (t, J = 7.6 Hz, 1H, CH arom.);
7.31–7.20 (m, 5H, CH arom.); 7.00 (d, J = 8.8 Hz, 2H, CH arom.);
6.74 (s, 1H, CHCO); 6.72 (s, 2H, CH arom.); 6.33 (d, J = 16.0 Hz,
1H, CH@CH); 4.68 (s, 2H, OCH2CO); 4.20–4.15 (m, 4H, CH2OCO);
3.87 (s, 6H, OCH3); 3.85 (s, 3H, OCH3); 3.53 (s, 2H, NCH2Ph);
2.42–2.38 (m, 4H, CH2N); 1.67–1.60 (m, 4H, CH2); 1.53–1.45 (m,