J. Liu et al.
Bioorganic Chemistry 112 (2021) 104956
H14), 5.32 – 5.30 (1H, m, H20), 5.19 – 5.16 (1H, m, H20), 4.09 – 4.02
(2H, m), 3.36 (1H, d, J = 5.8 Hz, H22), 2.32 (1H, q, J = 7.0 Hz, H11),
2.26 – 2.23 (1H, m, H2), 2.22 – 2.17 (1H, m, H4), 2.09 (2H, d, J = 9.1 Hz,
H10, H13), 1.79 – 1.75 (1H, m, H6), 1.67 – 1.65 (1H, m, H1), 1.65 – 1.62
(1H, m, H7), 1.56 (1H, dd, J = 14.1, 3.7 Hz, H13), 1.54 – 1.51 (1H, m),
1.46 – 1.45 (1H, m), 1.44 (3H, s), 1.39 (1H, d, J = 4.1 Hz, H15), 1.37
(1H, d, J = 5.8H8), 1.16 (3H, s), 1.13 (1H, dd, J = 14.2, 9.8 Hz, H18),
0.88 (3H, d, J = 7.1 Hz, H17), 0.75 (3H, d, J = 7.1, H16). 13C NMR (151
MHz, Chloroform-d) δ 216.69(C3), 166.04, 163.32, 162.73, 160.68,
158.96, 138.71(C19), 133.58, 133.53, 129.53, 124.67, 117.31(C20),
112.03, 74.59(C11), 70.93(C14), 58.06(C4), 45.42(C9), 44.63(C13),
44.00(C12), 41.90(C5), 36.66(C6), 36.03(C10), 35.03, 34.41(C2), 30.39
(C8), 26.83,(C7) 24.82(C18), 16.73(C16), 14.75(C15), 11.44(C17); HR-
MS (ESI): Calcd for C30H37FN2O5S (M+Na+): 579.2299; Found:
579.2288.
1.46 (2H, m, H13), 1.45 (3H, s), 1.38 (2H, dd, J = 15.4, 4.2 Hz, H15,
H8), 1.16 (3H, s), 1.12 (1H, dd, J = 14.1, 4.4 Hz, H18), 0.88 (3H, d, J =
7.0 Hz, H17), 0.75 (3H, d, J = 7.1 Hz, H16).13C NMR (151 MHz,
Chloroform-d) δ 216.71(C3), 166.04, 164.34, 163.46, 138.70(C19),
133.08, 132.46, 131.24, 130.98, 127.07, 122.79, 117.35(C20), 74.60
(C11), 70.95(C14), 58.07(C4), 45.42(C9), 44.64(C13), 44.00(C12),
41.90(C5), 36.66(C6), 36.03(C10), 35.03, 34.41(C2), 30.39(C8), 26.83
(C7), 26.39(C18), 24.82(C1), 16.76(C16), 14.77(C15), 11.44(C17); HR-
MS (ESI): Calcd for C30H37ClN2O5S (M+Na +): 595.2004; Found:
595.1993.
4.2.18. 22-[(3-chlorophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 128)
White powder; yield: 84%; 1H NMR (600 MHz, Chloroform-d) δ 7.99
(1H, td, J = 1.8, 0.5 Hz), 7.89 (1H, ddd, J = 7.8, 1.6, 1.1 Hz), 7.51 (1H,
ddd, J = 8.0, 2.1, 1.1 Hz), 7.48 – 7.39 (1H, m), 6.43 (1H, dd, J = 17.4,
11.0 Hz, H19), 5.79 (1H, d, J = 8.5, H14), 5.33 – 5.30 (1H, m, H20), 5.19
(1H, dd, J = 17.4, 1.5 Hz, H20), 4.12 – 4.00 (2H, m), 3.36 (1H, dd, J =
10.5, 6.5 Hz, H22), 2.35 – 2.29 (1H, m, H2), 2.28 – 2.22 (1H, m, H4),
2.19 (1H, dd, J = 19.5, 9.4 Hz, H10), 2.12 – 2.06 (2H, m, H13. 11-OH),
1.77 (1H, dq, J = 14.5, 3.1 Hz, H6, H8), 1.68 (1H, s, H1), 1.67 – 1.62
(1H, m, H7), 1.58 – 1.52 (1H, m), 1.51 – 1.46 (2H, m), 1.45 (3H, s, H13),
1.42 – 1.34 (2H, m, H15, H8), 1.17 (3H, s), 1.16 – 1.10 (1H, m, H18),
0.88 (3H, d, J = 7.1 Hz, H17), 0.76 (3H, d, J 7.1, H17).13C NMR (151
MHz, Chloroform-d) δ 216.69(C3), 165.99, 164.88, 163.32, 138.70
(C19), 135.25, 131.82, 130.44, 126.66, 125.05, 124.77, 117.36(C20),
74.59(C11), 71.00(C14), 58.06(C4), 45.42(C9), 44.65(C13), 44.01
(C12), 41.90(C5), 36.65(C6), 36.03(C10), 35.06, 34.41(C2), 30.38(C8),
26.83(C7), 26.41(C18), 24.82(C1), 16.76(C16), 14.77(C15), 11.44
(C17); HR-MS (ESI): Calcd for C30H37ClN2O5S (M+Na +): 595.2004;
Found: 595.1991.
4.2.15. 22-[(3-fluorophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 125)
White powder; yield: 82%; 1H NMR (600 MHz, Chloroform-d) δ 7.80
(1H, ddd, J = 7.8, 1.6, 1.0 Hz), 7.70 (1H, ddd, J = 9.1, 2.6, 1.5 Hz), 7.49
(1H, td, J = 8.0, 5.5 Hz), 7.24 (1H, tdd, J = 8.4, 2.6, 1.0 Hz), 6.43 (1H,
dd, J = 17.4, 11.0 Hz, H19), 5.80 (1H, d, J = 8.5 Hz, H14), 5.35 – 5.10
(2H, m, H20), 4.14 – 3.99 (2H, m), 3.36 (1H, dd, J = 10.4, 6.5 Hz, H22),
2.33 – 2.23 (2H, m, H2, H4), 2.19 (1H, dd, J = 19.5, 9.4 Hz, H10), 2.12 –
2.05 (2H, m, H13, 11-OH), 1.77 (1H, dq, J = 14.5, 3.2 Hz, H6), 1.67 (2H,
s H8), 1.67 – 1.62 (1H, m, H1), 1.59 – 1.51 (1H, m, H7), 1.50 – 1.46 (1H,
m, H13), 1.45 (3H, s), 1.42 – 1.34 (2H, m, H15, H8), 1.17 (3H, s), 1.13
(1H, dd, J = 14.2, 4.4 Hz, H18), 0.88 (3H, d, J = 7.1 Hz, H17), 0.76 (3H,
d, J = 7.1 Hz, H16). 13C NMR (151 MHz, Chloroform-d) δ 216.69(C3),
166.00, 165.05, 163.26, 161.99, 138.70(C19), 130.96, 130.91, 125.32,
122.45, 118.93, 118.79, 117.35(C20), 113.84, 113.68, 74.59(C11),
70.99(C14), 58.06(C4), 45.42(C9), 44.01(C12), 41.90(C5), 36.65(C6),
36.03(C10), 34.41(C2), 30.38(C8), 26.83(C7), 24.82, 16.76(C16), 14.76
(C15), 11.43(C17); HR-MS (ESI): Calcd for C30H37FN2O5S (M+Na +):
579.2299; Found: 579.2288.
4.2.19. 22-[(4-chlorophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 129)
White powder; yield: 82%; 1H NMR (600 MHz, Chloroform-d) δ 7.96
– 7.92 (2H, m), 7.51 – 7.47 (2H, m), 6.44 (1H, dd, J = 17.4, 11.0 Hz,
H19), 5.80 (1H, d, J = 8.5 Hz, H14), 5.34 – 5.31 (1H, m), 5.20 (1H, dd, J
= 17.4, 1.4 Hz, H20), 4.06 (2H, d, J = 3.0, H20, H22), 2.34 – 2.25 (2H,
m, H2, H4), 2.20 (1H, dd, J = 19.5, 9.4 Hz), 2.10 (2H, d, J = 8.7 Hz, H10,
H13), 1.78 (1H, dd, J = 14.5, 3.0 Hz, H6), 1.69 (2H, ddd, J = 12.9, 4.8,
2.8 Hz, H8), 1.60 – 1.54 (3H, m, 11-OH), 1.46 (3H, s, H1, H7), 1.41 –
1.35 (3H, m, H13, H15), 1.18 (3H, s, H8), 1.13 (1H, dd, J = 14.1, 4.4 Hz,
H18), 0.89 (3H, d, J = 7.1, H17), 0.77 (3H, d, J = 7.1, H16). 13C NMR
(151 MHz, Chloroform-d) δ 216.70(C3), 166.02, 165.24, 163.04, 138.71
(C19), 138.09, 129.48, 127.96, 121.91, 117.34(C20), 99.99, 74.59
(C11), 70.98(C14), 58.05(C4), 48.14, 45.42(C9), 44.64(C13), 44.01
(C12), 41.90(C5), 36.65(C6), 36.02(C10), 35.08, 34.41(C2), 30.38(C8),
26.83(C7), 26.42(C18), 24.81(C1), 16.76(C16), 14.77(C15), 11.44
(C17); HR-MS (ESI): Calcd for C30H37ClN2O5S (M+Na +): 595.2004;
Found: 595.1990.
4.2.16. 22-[(4-fluorophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 126)
White powder; yield: 78%; 1H NMR (600 MHz, Chloroform-d) δ 8.00
(2H, td, J = 5.2, 2.8 Hz), 7.21 – 7.18 (2H, m), 6.43 (1H, dd, J = 17.4,
11.0 Hz, H19), 5.79 (1H, d, J = 8.5 Hz), 5.32 – 5.30 (1H, m, H20), 5.19
(1H, d, J = 17.4 Hz, H20), 4.05 (2H, d, J = 3.3 Hz), 3.36 (1H, dd, J =
10.4, 6.5 Hz, H22), 2.32 (1H, q, J = 6.9 Hz), 2.29 – 2.22 (1H, m, H2),
2.19 (1H, dd, J = 19.5, 9.4 Hz, H4), 2.09 (2H, d, J = 16.5 Hz, H10, H13),
1.77 (1H, dd, J = 14.5, 2.9 Hz, H6), 1.71 (1H, s, H8), 1.67 – 1.64 (1H, m,
H1), 1.57 – 1.49 (2H, m, H7, H13), 1.47 (1H, d, J = 11.6 Hz), 1.45 (3H,
s), 1.38 (1H, d, J = 5.2 Hz, H15), 1.38 – 1.35 (1H, m, H8), 1.17 (3H, s),
1.16 – 1.10 (1H, m, H18), 0.88 (3H, d, J = 7.0 Hz, H17), 0.75 (3H, d, J =
7.1 Hz, H16). 13C NMR (151 MHz, Chloroform-d) δ 216.71(C3), 166.05,
165.63, 165.23, 163.95, 162.79, 138.72(C19), 129.04, 128.98, 117.33
(C20), 116.51, 116.36, 74.59(C11), 70.95(C14), 58.06(C4), 45.42(C9),
44.64(C13), 44.00(C12), 41.90(C5), 36.65(C6), 36.02(C10), 35.08,
34.41(C2), 30.38(C8), 26.83(C7), 26.41(C18), 24.81(C1), 16.75(C16),
14.77(C15), 11.43(C17); HR-MS (ESI): Calcd for C30H37FN2O5S (M+Na
+): 579.2299; Found: 579.2289.
4.2.20. 22-[(3-bromophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 130)
White powder; yield: 81%; 1H NMR (600 MHz, Chloroform-d) δ 8.15
– 8.14 (1H, m), 7.94 – 7.93 (1H, m), 7.67 – 7.66 (1H, m), 7.38 (1H, t, J =
7.9 Hz), 6.42 (1H, dd, J = 17.4, 11.0 Hz, H19), 5.79 (1H, d, J = 8.5 Hz),
5.31 (1H, dd, J = 9.6, 1.4 Hz, H14), 5.21 – 5.17 (1H, m, H20), 4.06 (2H,
d, J = 3.2, H20, H22), 3.36 (1H, d, J = 6.4, H11), 2.34 – 2.30 (1H, m,
H2), 2.26 – 2.23 (1H, m, H4), 2.20 (1H, q, J = 9.7, H10), 2.10 (2H, d, J =
8.6 Hz, H13), 1.79 – 1.75 (1H, m, H6), 1.67 (1H, dd, J = 5.2, 3.0 Hz, H8),
1.56 (1H, dd, J = 13.9, 3.7 Hz), 1.54 – 1.49 (2H, m), 1.48 – 1.46 (1H, m,
H1), 1.45 (3H, s, H7, H13), 1.39 (1H, d, J = 5.7, H15), 1.37 (1H, d, J =
7.9 Hz), 1.17 (3H, s), 1.12 (1H, dd, J = 14.1, 4.4 Hz, H8), 0.88 (3H, d, J
= 7.1, H17), 0.76 (3H, d, J = 7.1 Hz, H16). 13C NMR (151 MHz, Chlo-
roform-d) δ 216.66(C3), 165.97, 164.72, 163.32, 138.71(C19), 134.73,
130.63, 129.52, 125.27, 125.20, 123.11, 117.35(C20), 74.59(C11),
4.2.17. 22-[(2-chlorophenyl-1, 3, 4-oxadiazol-5-yl) thio] deoxy
pleuromutilin (compound 127)
White powder; yield: 80%; 1H NMR (600 MHz, Chloroform-d) δ 7.93
(1H, dd, J = 7.8, 1.7 Hz), 7.55 (1H, dd, J = 8.1, 1.3 Hz), 7.48 (1H, ddd, J
= 8.0, 7.4, 1.7 Hz), 7.41 (1H, td, J = 7.6, 7.6, 1.3 Hz), 6.43 (1H, dd, J =
17.4, 11.0 Hz, H19), 5.80 (1H, d, J = 8.5H14), 5.36 – 5.14 (2H, m, H20),
4.14 – 4.00 (2H, m), 3.36 (1H, dd, J = 10.6, 6.5 Hz), 2.32 (1H, p, J = 7.5,
7.5, 7.3, 7.3 Hz, H2), 2.27 – 2.22 (1H, m, H4), 2.19 (1H, dd, J = 19.5,
9.4 Hz, H10), 2.13 – 2.04 (2H, m, H13, 11-OH), 1.77 (1H, dq, J = 14.6,
3.2, 3.2, 3.2 Hz, H6), 1.67 (2H, s, H1, H7), 1.59 – 1.51 (1H, m), 1.50 –
10