C. Zhao et al.
Bioorganic & Medicinal Chemistry 40 (2021) 116185
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H NMR(400 MHz, Acetone‑d6) δ 9.28(s, 1H, CONH ), 7.66(d, J =
136.71, 129.30, 129.05, 128.99, 128.55, 128.10, 127.35, 125.81,
123.75, 122.95, 119.25, 119.04, 115.67, 115.44, 84.16, 82.62, 61.86,
36.72, 33.32, 30.49, 30.33, 29.65, 28.44, 25.24, 25.21, 24.60, 20.34;
HRMS(ESI) calcd for C35H39N2O7S [M - H]-, 647.2478; found 631.2483.
8-(4-(6-(N-Ethyl-N-(4-methoxyphenyl)sulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
8.4 Hz, 2H), 7.51(d, J = 8.8 Hz, 2H), 7.37(d, J = 8.0 Hz, 2H), 7.27(d, J =
8.4 Hz, 2H), 7.24(d, J = 8.8 Hz, 2H), 6.84(d, J = 8.4 Hz, 2H), 5.58(s,
1H), 5.38(s, 1H), 3.68(m, 3H), 2.39(t, J = 7.6 Hz, 3H), 2.29(t, J = 7.2
Hz, 2H), 2.27(m, 1H), 1.69(t, J = 6.8 Hz, 2H), 1.60(t, J = 7.2 Hz, 2H),
1.37(m, 4H), 1.05(t, J = 7.2 Hz, 3H). 13C NMR(100 MHz, Acetone‑d6) δ
175.21, 172.53, 158.53, 143.17, 141.57, 139.98, 139.18, 137.90,
133.55, 131.63, 131.59, 130.11, 129.95, 129.64, 128.89, 128.43,
124.86, 124.21, 120.36, 120.16, 116.64, 116.45, 85.25, 83.63, 62.68,
47.04, 37.73, 34.12, 31.38, 31.18, 29.67, 26.17, 25.54, 14.84; HRMS
(ESI) calcd for C34H36ClN2O7S [M - H]-, 651.1932; found 651.1937.
8-(4-(6-(N-(2-bromophenyl)-N-ethylsulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
oxooctanoic acid (17d). Pale yellow solid, 91% yield, m.p. 141–143 ◦C;
1
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H NMR(400 MHz, Acetone‑d6) δ 9.16(s, 1H, CONH ), 7.50(d, J =
8.8 Hz, 1H), 7.46(d, J = 8.8 Hz, 1H), 7.12(d, J = 8.4 Hz, 2H), 7.11(d, J =
8.0 Hz, 2H), 7.09(d, J = 8.4 Hz, 1H), 7.06(d, J = 8.0 Hz, 1H), 6.72(d, J =
8.8 Hz, 2H), 6.70(d, J = 8.8 Hz, 1H), 6.66(d, J = 8.4 Hz, 1H), 5.35(s,
1H), 5.20(s, 1H), 3.64(m, 2H), 3.62(s, 3H), 3.37(m, 1H), 2.23(m, 2H),
2.14(t, J = 6.8 Hz, 2H), 2.07(m, 1H), 1.91(m, 1H), 1.54(m, 2H), 1.45(t,
J = 6.4 Hz, 2H), 1.23(m, 4H), 0.88(t, J = 7.2 Hz, 3H). 13C NMR(100
MHz, Acetone‑d6) δ 175.10, 172.48, 159.91, 158.40, 143.10, 141.52,
140.11, 139.95, 138.05, 132.56, 131.50, 130.18, 129.55, 128.99,
128.36, 124.96, 124.29, 120.39, 120.16, 116.66, 116.46, 115.00, 85.32,
83.64, 62.13, 55.80, 47.36, 37.72, 34.25, 31.36, 31.18, 26.16, 25.54,
20.64, 14.97
oxooctanoic acid (17i). Pale yellow solid, 89% yield, m.p. 145–147 ◦C;
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H NMR(400 MHz, Acetone‑d6) δ 9.25(s, 1H, CONH ), 7.65(d, J =
8.0 Hz, 3H), 7.35(m, 2H), 7.29(d, J = 8.4 Hz, 3H), 7.21(d, J = 8.0 Hz,
2H), 6.83(d, J = 8.8 Hz, 2H), 5.61(s, 1H), 5.39(t, J = 3.2 Hz, 1H), 3.84
(m, 1H), 3.70(m, 2H), 2.40(t, J = 7.2 Hz, 2H), 2.30(t, J = 7.6 Hz, 2H),
2.20(m, 1H), 2.07(m, 1H), 1.70(t, J = 6.4 Hz, 2H), 1.61(t, J = 6.8 Hz,
2H), 1.39(m, 4H), 1.08(t, J = 6.8 Hz, 3H). 13C NMR(100 MHz, Ace-
tone‑d6) δ 174.16, 171.55, 157.67, 142.17, 140.54, 139.08, 138.79,
137.36, 136.62, 129.55, 128.98, 128.64, 127.96, 127.43, 123.91,
123.23, 119.34, 119.15, 115.68, 115.50, 84.38, 82.64, 61.28, 46.21,
36.77, 33.35, 28.73, 25.23, 24.62, 20.15, 19.76, 14.02; HRMS(ESI)
calcd for C34H36BrN2O7S [M - H]-, 695.1427; found 695.1432.
8-(4-(6-(N-Ethyl-N-(3-methoxyphenyl)sulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
oxooctanoic Acid (17e). Pale yellow solid, 94% yield, m.p.
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–
145–148 C; H NMR(400 MHz, Acetone‑d6) δ 9.15(s, 1H, CONH ),
7.48(d, J = 8.8 Hz, 2H), 7.12(t, J = 8.0 Hz, 3H), 7.06(d, J = 8.0 Hz, 2H),
6.82(d, J = 8.0 Hz, 2H), 6.73(d, J = 8.4 Hz, 1H), 6.66(d, J = 8.8 Hz, 2H),
5.37(s, 1H), 5.19(s, 1H), 3.70(m, 2H), 3.60(s, 3H), 3.42(m, 1H), 2.23(m,
2H), 2.14(t, J = 7.2 Hz, 2H), 2.05(m, 1H), 1.91(m, 1H), 1.54(m, 2H),
1.45(t, J = 6.8 Hz, 2H), 1.23(m, 4H), 0.90(t, J = 6.8 Hz, 3H). 13C NMR
(100 MHz, Acetone‑d6) δ 175.08, 172.46, 161.04, 158.42, 143.22,
141.42, 139.98, 139.71, 138.02, 130.47, 130.02, 129.63, 128.81,
128.42, 124.94, 124.25, 121.77, 120.30, 116.64, 116.46, 115.93,
113.86, 85.24, 83.68, 62.66, 55.75, 47.03, 37.72, 34.24, 32.67, 31.18,
26.15, 25.54, 20.63, 14.94; HRMS(ESI) calcd for C35H39N2O8S [M - H]-,
647.2428; found 647.2433.
8-((4-(-3-(4-Hydroxyphenyl)-6-(N-phenyl-N-(2,2,2-tri-
fluoroethyl)sulfamoyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenyl)
amino)-8-oxooctanoic acid (18a). Pale yellow solid, 97% yield, m.p.
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122–125 C; H NMR(400 MHz, Acetone‑d6) δ 9.33(s, 1H, CONH ),
7.64(d, J = 8.8 Hz, 1H), 7.61(d, J = 8.8 Hz, 1H), 7.46(t, J = 8.4 Hz, 2H),
7.35(m, 3H), 7.25(d, J = 8.0 Hz, 1H), 7.23(d, J = 8.4 Hz, 1H), 7.20(d, J
= 8.0 Hz, 1H), 7.19(d, J = 8.0 Hz, 1H), 6.85(d, J = 8.8 Hz, 1H), 6.81(d, J
= 8.4 Hz, 1H), 5.56(s, 1H), 5.36(s, 1H), 4.59(m, 2H), 3.63(m, 1H), 2.37
(t, J = 7.6 Hz, 2H), 2.28(m, 2H), 2.15(m, 1H), 2.06(m, 1H), 1.68(t, J =
7.2 Hz, 2H), 1.60(m, 2H), 1.37(m, 4H). 13C NMR(100 MHz, Acetone‑d6)
δ 174.91, 172.24, 158.56, 143.32, 141.80, 140.50, 139.40, 137.73,
130.21, 129.87, 129.82, 129.53, 129.19, 129.01, 128.72, 128.32,
128.09, 124.75, 124.05, 120.15, 119.92, 116.57, 116.37, 85.18, 83.57,
63.01, 37.63, 34.17, 31.41, 31.25, 29.64, 29.56, 26.09, 25.51; HRMS
(ESI) calcd for C34H34F3N2O7S [M - H]-, 671.2039; found 671.2044.
8-(4-(3-(4-Hydroxyphenyl)-6-(N-(m-tolyl)-N-(2,2,2-tri-
8-(4-(-6-(N-(4-Hydroxyphenyl)-N-ethylsulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
oxooctanoic acid (17f). Pale yellow solid, 93% yield, m.p. 151–153 ◦C;
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H NMR(400 MHz, Acetone‑d6) δ 9.35(s, 1H, CONH ), 7.66(d, J =
8.0 Hz, 2H), 7.29(d, J = 8.8 Hz, 2H), 7.22(d, J = 8.8 Hz, 2H), 7.15(d, J =
8.8 Hz, 2H), 6.81(d, J = 8.4 Hz, 2H), 6.77(d, J = 8.0 Hz, 2H), 5.49(s,
1H), 5.35(t, J = 3.6 Hz, 1H), 3.76(m, 2H), 3.53(m, 1H), 2.42(t, J = 7.2
Hz, 2H), 2.29(t, J = 7.2 Hz, 2H), 2.23(m, 1H), 2.06(m, 1H), 1.70(t, J =
7.6 Hz, 2H), 1.62(t, J = 6.8 Hz, 2H), 1.37(m, 4H), 1.02(t, J = 7.2 Hz,
3H). 13C NMR(100 MHz, Acetone‑d6) δ 175.06, 172.48, 158.53, 157.83,
141.48, 139.94, 139.79, 131.68, 131.47, 130.17, 129.08, 128.37,
124.28, 120.12, 116.63, 116.45, 84.14, 83.58, 61.97, 47.38, 37.71,
34.24, 31.36, 30.70, 29.65, 26.15, 25.54, 14.90; HRMS(ESI) calcd for
fluoroethyl)sulfamoyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenyl-
amino)-8-oxooctanoic acid (18b). Pale yellow solid, 95% yield, m.p.
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124–126 C; H NMR(400 MHz, Acetone‑d6) δ 9.29(s, 1H, CONH ),
7.64(m, 2H), 7.30(d, J = 8.0 Hz, 2H), 7.21(d, J = 8.4 Hz, 2H), 7.21(m,
2H), 7.12(d, J = 8.4 Hz, 1H), 7.08(d, J = 8.4 Hz, 1H), 6.85(d, J = 8.4 Hz,
1H), 6.82(d, J = 8.4 Hz, 1H), 5.56(s, 1H), 5.36(s, 1H), 4.51(m, 2H), 3.63
(m, 1H), 2.39(t, J = 7.6 Hz, 2H), 2.33(m, 2H), 2.31(m, 3H), 2.18(m, 1H),
1.98(m, 1H), 1.70(t, J = 6.4 Hz, 2H), 1.60(t, J = 6.4 Hz, 2H), 1.38(m,
4H). 13C NMR(100 MHz, Acetone‑d6) δ 175.28, 172.67, 157.61, 143.40,
141.49, 140.14, 139.27, 137.81, 131.18, 130.79, 130.55, 130.28,
129.53, 129.09, 126.55, 126.36, 124.77, 124.09, 120.21, 116.67,
116.48, 116.24, 85.24, 83.56, 62.86, 37.75, 34.27, 29.66, 26.22, 26.20,
26.17, 25.54, 21.11, 20.68; HRMS(ESI) calcd for C35H36F3N2O7S [M -
H]-, 685.2206; found 685.2201.
C
34H37N2O8S [M - H]-, 633.2271; found 633.2276.
8-(4-(-6-(N-(3-Chlorophenyl)-N-ethylsulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabic-yclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
oxooctanoic acid (17g). Pale yellow solid, 87% yield, m.p. 144–146 ◦C;
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H NMR(400 MHz, Acetone‑d6) δ 9.29(s, 1H, CONH ), 7.64(d, J =
8.8 Hz, 1H), 7.61(d, J = 8.8 Hz, 1H), 7.39(m, 4H), 7.27(d, J = 8.4 Hz,
1H), 7.25(d, J = 8.4 Hz, 1H), 7.22(d, J = 8.0 Hz, 1H), 7.20(d, J = 8.0 Hz,
1H), 6.82(d, J = 8.8 Hz, 1H), 6.78(d, J = 8.8 Hz, 1H), 5.52(s, 1H), 5.36
(s, 1H), 3.84(m, 2H), 3.56(m, 1H), 2.38(m, 2H), 2.29(t, J = 7.2 Hz, 2H),
2.13(m, 1H), 2.07(m, 1H), 1.70(m, 2H), 1.60(t, J = 6.4 Hz, 2H), 1.37(m,
4H), 1.03(t, J = 6.8 Hz, 3H). 13C NMR(100 MHz, Acetone‑d6) δ 175.08,
172.49, 158.50, 143.36, 141.77, 140.11, 139.84, 138.13, 137.27,
135.81, 134.24, 131.36, 130.73, 129.63, 128.60, 128.40, 124.97,
124.28, 120.27, 120.15, 116.62, 116.47, 85.48, 83.70, 63.85, 47.09,
37.73, 34.23, 29.67, 26.20, 26.16, 25.54, 20.66, 14.64; HRMS(ESI)
calcd for C34H36ClN2O7S [M - H]-, 651.1932; found 651.1937.
8-(4-(3-(4-Hydroxyphenyl)-6-(N-(m-tolyl)-N-(2,2,2-tri-
fluoroethyl)sulfamoyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenyl-
amino)-8-oxooctanoic acid (18c). Pale yellow solid, 94% yield, m.p.
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123–125 C; H NMR(400 MHz, Acetone‑d6) δ 9.27(s, 1H, CONH ),
7.66(d, J = 8.0 Hz, 1H), 7.61(d, J = 8.0 Hz, 1H), 7.35(m, 1H), 7.27(d, J
= 8.8 Hz, 2H), 7.24(d, J = 8.4 Hz, 2H), 7.22(m, 2H), 7.05(t, J = 8.0 Hz,
1H), 6.86(d, J = 8.8 Hz, 1H), 6.81(d, J = 8.8 Hz, 1H), 5.59(s, 1H), 5.36
(s, 1H), 4.58(m, 2H), 3.63(m, 1H), 2.38(t, J = 7.2 Hz, 2H), 2.30(m, 2H),
2.27(s, 3H), 2.21(m, 1H), 2.10(m, 1H), 1.70(t, J = 6.4 Hz, 2H), 1.62(m,
2H), 1.40(m, 4H). 13C NMR(100 MHz, Acetone‑d6) δ 175.00, 172.45,
158.47, 143.10, 141.55, 140.03, 139.58, 137.90, 129.99, 129.85,
8-(4-(-6-(N-(4-chlorophenyl)-N-ethylsulfamoyl)-3-(4-hydrox-
yphenyl)-7-oxabicyclo[2.2.1]hept-2-en-2-yl)phenylamino)-8-
oxooctanoic acid (17h). Pale yellow solid, 90% yield, m.p. 141–143 ◦C;
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