Q. Hou et al.
Bioorganic & Medicinal Chemistry 28 (2020) 115763
4.1.8. Synthesis of N-(2-((E)-3-(2-methoxyphenyl) acrylamido) ethyl)-3-
oxo-4-ene-androstane-17-carboxamide (8)
4.1.14. Synthesis of N-(2-((E)-3- N-(2-((E)-3-(4-(nitrophenyl) phenyl)
acrylamido) ethyl)-3-oxo-4-ene-androstane-17-carboxamide (14)
The synthesis of target compound 14 was similar to the procedure as
described for 7. Yellow solid: 87 mg; yield: 25%. m.p.: 128–130 ℃; 1H
NMR (300 MHz, DMSO‑d6) δ 8.44–8.22 (m, 3H), 7.98–7.77 (m, 2H),
The target compound 8 was synthesized according to the procedure
of 7. Light yellow solid: 205 mg; yield: 61%. m.p.: 136–138 ℃; 1H NMR
(300 MHz, DMSO‑d6) δ 8.14 (d, J = 5.5 Hz, 1H), 7.69 (d, J = 16.1 Hz,
1H), 7.58–7.46 (m, 2H), 7.47–7.24 (m, 1H), 7.10 (d, J = 8.3 Hz, 1H),
7.01 (t, J = 7.5 Hz, 1H), 6.65 (dd, J = 15.9, 2.4 Hz, 1H), 5.64 (s, 1H),
3.88 (d, J = 2.4 Hz, 3H). 13C NMR (75 MHz, DMSO) δ 198.46, 172.29,
171.41, 166.13, 157.98, 134.14, 131.27, 128.19, 123.68, 122.87,
121.15, 112.12, 56.01, 55.35, 53.66, 43.70. HRMS(ESI) m/z calcd for
7.57 (d, J = 16.3 Hz, 2H), 6.83 (d, J = 15.8 Hz, 1H), 5.64 (s, 1H). 13
C
NMR (75 MHz, DMSO) δ 198.52, 172.37, 171.43, 165.04, 147.94,
141.99, 136.88, 129.08, 126.85, 124.61, 123.61, 56.02, 55.35, 53.65,
43.71, 40.47. HRMS(ESI)m/z calcd for C31H39N3O5[M+H]+ 534.6690,
found 534.2971.
C
32H42N2O4[M+H]+ 519.6980, found 519.3221.
4.1.15. Synthesis of N-(2-((E)-3- N-(2-((E)-3-(3-(nitrophenyl) phenyl)
acrylamido) ethyl)-3-oxo-4-ene-androstane-17-carboxamide (15)
4.1.9. Synthesis of N-(2-((E)-3-(4-methoxyphenyl) acrylamido) ethyl) ꢀ 3-
oxo-4-ene-androstane-17-carboxamide (9)
The synthesis of target compound 15 was similar to the procedure as
described for 7. Yellow solid: 105 mg; yield: 30%. m.p.: 128–130 ℃; 1H
NMR (400 MHz, DMSO‑d6) δ 8.40 (t, J = 2.0 Hz, 1H), 8.26–8.16 (m, 2H),
8.03 (dt, J = 7.8, 1.3 Hz, 1H), 7.72 (t, J = 8.0 Hz, 1H), 7.56 (d, J = 15.8
Hz, 1H), 7.49 (t, J = 5.5 Hz, 1H), 6.81 (d, J = 15.8 Hz, 1H), 5.61 (d, J =
1.6 Hz, 1H). 13C NMR (101 MHz, DMSO) δ 198.43, 172.35, 171.36,
165.17, 148.75, 137.28, 136.85, 134.29, 131.00, 125.52, 124.18,
123.59, 122.04, 56.03, 55.36, 53.66, 43.71. HRMS(ESI) m/z calcd for
The synthesis of target compound 9 was similar to the procedure as
described for 7. Light yellow solid: 180 mg; yield: 53%. m.p.: 116–118
ꢀ; 1H NMR (300 MHz, DMSO‑d6) δ 8.13 (d, J = 5.2 Hz, 1H), 7.55 (d, J =
7.9 Hz, 3H), 7.44 (s, 1H), 7.01 (d, J = 8.3 Hz, 2H), 6.49 (d, J = 15.7 Hz,
1H), 5.65 (s, 1H), 3.82 (s, 3H). 13C NMR (75 MHz, DMSO) δ 198.58,
172.35, 171.50, 166.12, 160.80, 138.96, 129.60, 127.91, 123.62,
120.03, 114.83, 55.72, 53.68, 43.73. HRMS(ESI) m/z calcd for
C
32H42N2O4[M+H]+ 519.6980, found 519.3225.
C
31H39N3O5[M+H]+ 534.6690, found 534.2966.
4.1.10. Synthesis of N-(2-((E)-3-(3,4-dimethoxyphenyl) acrylamido)
ethyl) ꢀ 3-oxo-4-ene-androstane-17-carboxamide (10)
4.1.16. Synthesis of 17β-(N-Boc-ethylenediamine formyl) androstane-1,4-
diene-3-one (16)
The synthesis of target compound 10 was similar to the procedure as
described for 7. Light yellow solid: 99 mg; yield: 28%. m.p.: 124–126
ꢀ;1H NMR (300 MHz, DMSO‑d6) δ 7.86 (d, J = 5.4 Hz, 1H), 7.30 (t, J =
5.4 Hz, 1H), 7.16 (d, J = 15.7 Hz, 1H), 7.00–6.89 (m, 2H), 6.78 (d, J =
8.2 Hz, 1H), 6.29 (d, J = 15.7 Hz, 1H), 5.41 (s, 1H), 3.58 (d, J = 3.4 Hz,
6H). 13C NMR (75 MHz, DMSO) δ 198.64, 172.42, 171.58, 166.18,
150.55, 149.32, 139.37, 128.08, 123.58, 121.84, 120.14, 112.07,
110.38, 55.96, 55.83, 55.32, 53.66, 43.72. HRMS(ESI) m/z calcd for
To a solution of compound 6 (4 g, 8.67 mmol), TBDMSCl (65 mg,
0.43 mmol) in 1,4-dioxane was added DDQ (2.5 g, 11.2 mmol). The
mixture was refluxed for about 2 h in a N2 atmosphere. After the reaction
was cooled to room temperature, the solution was filtered and filtrate
was evaporated to dry to give the compound 16. The crude product was
purified by column chromatography. White solid: 2.2 g; yield: 56%.1H
NMR (300 MHz, DMSO‑d6) δ 7.48 (s, 1H), 7.20 (d, J = 10.1 Hz, 1H), 6.76
(s, 1H), 6.13 (dd, J = 10.3, 1.9 Hz, 1H), 5.99 (s, 1H).
C
33H44N2O5[M+H]+ 549.7240, found 549.3335.
4.1.17. Synthesis of N-(2-cinnamamidoethyl)-3-oxo-1,4-diene-androstane-
17-carboxamide (17)
4.1.11. Synthesis of N-(2-((E)-3-(3,4,5-trimethoxy) acrylamido) ethyl)-3-
oxo-4-ene-androstane-17-carboxamide (11)
The detailed procedure of synthesizing target compound 17 was
referred to the procedure of 7. White solid: 180 mg; yield: 57%. m.p.:
120–122 ℃; 1H NMR (400 MHz, DMSO‑d6) δ 8.15 (s, 1H), 7.70–7.29 (m,
7H), 7.22–6.97 (m, 1H), 6.73–6.50 (m, 1H), 6.30–5.83 (m, 2H). 13C
NMR (101 MHz, DMSO) δ 185.44, 172.27, 169.89, 165.75, 156.83,
139.17, 135.40, 129.91, 129.41, 127.98, 127.19, 123.51, 122.64, 55.98,
54.93, 52.52, 44.20, 43.94, 43.66. HRMS(ESI) m/z calcd for
The synthesis of target compound 11 was similar to the procedure as
described for 7. Light brown solid: 207 mg; yield: 55%. m.p.: 126–128
ꢀ; 1H NMR (400 MHz, DMSO‑d6) δ 8.05 (t, J = 5.4 Hz, 1H), 7.47 (t, J =
5.4 Hz, 1H), 7.37 (d, J = 15.7 Hz, 1H), 6.90 (s, 2H), 6.56 (d, J = 15.7 Hz,
1H), 5.66–5.51 (m, 1H), 3.81 (s, 5H), 3.68 (s, 3H). 13C NMR (101 MHz,
DMSO) δ 198.45, 172.32, 171.41, 165.85, 153.55, 139.35, 139.10,
131.00, 123.59, 121.88, 105.37, 60.55, 56.32, 56.04, 55.37, 53.67,
43.72. HRMS (ESI) m/z calcd for C34H46N2O6[M+H]+ 579.7550, found
579.3435.
C
31H38N2O3[M+H]+ 487.2560, found 487.2964.
4.1.18. Synthesis of N-(2-((E)-3-(2-methoxyphenyl) acrylamido) ethyl)-3-
oxo-1,4-diene-androstane-17-carboxamide (18)
4.1.12. Synthesis of N-(2-((E)-3-(4-chlorophenyl) acrylamido) ethyl)-3-
oxo-4-ene-androstane-17-carboxamide (12)
The target compound 18 was synthesized according to the procedure
of 7. Beige solid: 205 mg; yield: 61%. m.p.: 208–210 ℃; 1H NMR (300
MHz, DMSO‑d6) δ 8.18 (d, J = 5.6 Hz, 1H), 7.56 (q, J = 5.9 Hz, 1H),
7.48–7.29 (m, 2H), 7.24–7.12 (m, 2H), 7.09 (dd, J = 10.2, 3.1 Hz, 1H),
6.97 (dd, J = 8.1, 2.5 Hz, 1H), 6.63 (d, J = 15.8 Hz, 1H), 6.11 (dd, J =
10.2, 1.9 Hz, 1H), 5.98 (d, J = 2.1 Hz, 1H), 3.80 (s, 3H). 13C NMR (75
MHz, DMSO) δ 185.47, 172.26, 170.00, 165.70, 160.05, 156.92, 139.12,
136.80, 130.47, 127.16, 123.50, 122.89, 120.29, 115.62, 113.18, 55.92,
55.55, 54.87, 52.45, 44.19, 43.94, 43.65. HRMS(ESI)m/z calcd for
The synthesis of target compound 12 was similar to the procedure as
described for 7. White solid: 146 mg; yield: 43%. m.p.: 206–208 ℃; 1H
NMR (300 MHz, DMSO‑d6) δ 8.17 (s, 1H), 7.66–7.59 (m, 2H), 7.52–7.37
(m, 4H), 6.63 (d, J = 15.8 Hz, 1H), 5.64 (s, 1H).13C NMR (101 MHz,
DMSO) δ 198.47, 172.34, 171.41, 165.54, 137.82, 134.33, 129.69,
123.39, 56.03, 55.36, 53.66, 43.71, 40.38. HRMS(ESI) m/z calcd for
C
31H39ClN2O3[M+H]+ 523.1140, found 523.2733.
C
32H40N2O4[M+H]+ 517.3065, found 517.3068.
4.1.13. Synthesis of N-(2-((E)-3- N-(2-((E)-3-(4-(trifluoromethyl) phenyl)
acrylamido) ethyl)-3-oxo-4-ene-androstane-17-carboxamide (13)
4.1.19. Synthesis of N-(2-((E)-3-(4-methoxyphenyl) acrylamido) ethyl)
ꢀ 3-oxo-1,4-ene-androstane-17-carboxamide (19)
The synthesis of target compound 13 was similar to the procedure as
described for 7. Light brown solid: 92 mg; yield: 25%. m.p.: 108–110 ℃;
1H NMR (300 MHz, DMSO‑d6) δ 8.26 (d, J = 5.5 Hz, 1H), 7.79 (s, 4H),
7.57–7.43 (m, 2H), 6.76 (d, J = 15.8 Hz, 1H), 5.62 (s, 1H). 13C NMR (75
MHz, DMSO) δ 198.43, 172.35, 171.37, 165.27, 139.44, 137.50, 128.62,
126.36, 126.24, 125.38, 123.60, 56.02, 55.35, 53.65, 43.70. HRMS(ESI)
m/z calcd for C32H39F3N2O3[M+H]+ 557.6702, found 557.2981.
The synthesis of target compound 19 was similar to the procedure as
described for 7. Beige solid: 183 mg; yield: 54%.m.p.: 128–130 ℃; 1H
NMR (400 MHz, DMSO‑d6) δ 8.04 (s, 1H), 7.62–7.30 (m, 4H), 7.18–6.87
(m, 3H), 6.49 (d, J = 13.9 Hz, 1H), 6.05 (dt, J = 53.7, 9.2 Hz, 3H), 3.80
(dt, J = 10.7, 5.3 Hz, 3H). 13C NMR (101 MHz, DMSO) δ 185.44, 172.28,
169.93, 166.06, 160.80, 156.88, 138.88, 129.56, 127.96, 127.17,
7