S.-Y. Huang et al.
Bioorganic & Medicinal Chemistry 38 (2021) 116138
+
(
C15), 11.44 (C17). HR-MS (ESI): Calcd for C32
H
42
N
4
O
5
S (M-H ):
H2, H4, H6, H10, 11-OH) , 1.76 – 1.44 (4H, m, H1, H7), 1.43 (3H, s,
H15), 1.40 – 1.12 (4H, m, H8, H13), 1.09 (3H, s, H18), 0.87 (3H, dd, J =
5
93.2798; Found: 593.2557.
1
3
7
.1, 3.0 Hz, H17), 0.69 (3H, d, J = 7.0 Hz, H16). C NMR (101 MHz,
4
2
.2.5. 22-(3-amino-2-(3-methyl-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-
2-deoxypleuromutilin (11)
Chloroform-d) δ 216.96 (C3), 167.28 (C21), 165.95, 163.23, 161.09,
158.64, 138.96 (C19), 129.83, 129.76, 127.18, 120.64, 118.56, 117.12
(C20), 74.55 (C11), 70.04 (C14), 58.12 (C4), 45.42 (C9), 44.55 (C13),
43.87 (C12), 41.85 (C5), 36.71 (C6), 35.98 (C10), 34.44 (C2), 33.89
(C22), 30.39 (C8), 26.82 (C7), 26.34 (C18), 24.81 (C1), 16.68 (C16),
White powder; yield: 30.7%; 1H NMR (600 MHz, Chloroform-d) δ
.04 – 7.95 (2H, m), 7.39 (2H, dt, J = 15.2, 7.6, 7.6 Hz), 6.75 (2H, s),
.42 (1H, dd, J = 17.4, 11.0 Hz, H19), 5.73 (1H, d, J = 8.5 Hz, H14),
.26 (1H, dd, J = 11.0, 1.5 Hz, H20), 5.12 (1H, dd, J = 17.4, 1.6 Hz,
8
6
5
14.81 (C15), 11.44 (C17). HR-MS (ESI): Calcd for C31
H
4
39FN O
5
S (M-
+
H20), 3.81 (2H, s, H22), 3.33 (1H, s, H11), 2.44 (3H, s, H32), 2.36 – 1.97
H ): 597.2547; Found: 597.2556.
(
(
5H, m, H2, H4, H10, 11-OH), 1.82 – 1.44 (6H, m, H1, H6, H7, H8), 1.42
3H, s, H15), 1.37 – 1.10 (3H, m, H8, H13), 1.07 (3H, s, H18), 0.86 (3H,
4.2.9. 22-(3-amino-2-(4-fluoro-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-
22-deoxypleuromutilin (15)
1
3
d, J = 7.0 Hz, H17), 0.69 (3H, d, J = 7.0 Hz, H16). C NMR (101 MHz,
Chloroform-d) δ 216.96 (C3), 167.69, 167.32 (C21), 160.39, 158.67,
White powder; yield: 34.1%; 1H NMR (600 MHz, Chloroform-d) δ
8.36 – 8.27 (2H, m), 7.18 (2H, t, J = 8.7, 8.7 Hz), 6.64 (2H, s), 6.49 –
6.37 (1H, m, H19), 5.74 (1H, d, J = 8.5 Hz, H14), 5.26 (1H, dd, J = 11.0,
1.6 Hz, H20), 5.13 (1H, dd, J = 17.5, 1.7 Hz, H20), 3.81 (2H, d, J = 1.6
Hz, H22), 3.34 (1H, dd, J = 10.6, 6.5 Hz, H11), 2.36 – 1.94 (5H, m, H2,
H4, H10, 11-OH), 1.81 – 1.44 (6H, m, H1, H6, H7, H13), 1.43 (3H, s,
H15), 1.37 – 1.10 (3H, m, H8, H13), 1.08 (3H, s, H18), 0.87 (3H, d, J =
1
38.94 (C19), 137.95, 134.18, 131.66, 131.22, 128.51, 127.96, 117.09
C20), 74.56 (C11), 69.98 (C14), 58.13 (C4), 45.42 (C9), 44.52 (C13),
3.87 (C12), 41.85 (C5), 36.72 (C6), 35.98 (C10), 34.44 (C2), 33.95
C22), 30.39 (C8), 26.82 (C7), 26.37 (C18), 24.81 (C1), 21.35, 16.66
(
4
(
(
(
C16), 14.83 (C15), 11.44 (C17). HR-MS (ESI): Calcd for C32
H
42
N
4
O
5
S
+
M-H ): 593.2798; Found: 593.2808.
1
3
7
.0 Hz, H17), 0.74 – 0.63 (3H, m, H16). C NMR (101 MHz, Chloro-
4
2
.2.6. 22-(3-amino-2-(4-methyl-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-
form-d) δ 216.92 (C3), 167.30 (C21), 167.10, 166.06, 161.14, 158.67,
138.97 (C19), 134.40, 134.30, 127.37, 117.11 (C20), 115.52, 115.31,
74.54 (C11), 70.03 (C14), 58.12 (C4), 45.42 (C9), 44.55 (C13), 43.87
(C12), 41.85 (C5), 36.69 (C6), 35.99 (C10), 34.43 (C2), 33.91 (C22),
2-deoxypleuromutilin (12)
White powder; yield: 36.3%; 1H NMR (600 MHz, Chloroform-d) δ
.15 – 8.11 (2H, m), 7.29 (2H, d, J = 8.1 Hz), 6.76 (2H, s), 6.43 (1H, dd,
8
J = 17.4, 11.0 Hz, H19), 5.74 (1H, d, J = 8.5 Hz, H14), 5.26 (1H, dd, J =
30.38 (C8), 26.83 (C7), 26.36 (C18), 24.81 (C1), 16.69 (C16), 14.83
+
1
1.0, 1.5 Hz, H20), 5.13 (1H, dd, J = 17.4, 1.5 Hz, H20), 3.82 (2H, d, J
1.1 Hz, H22), 3.36 – 3.31 (1H, m, H11), 2.45 (3H, s, H32), 2.32 – 1.98
5H, m, H2, H4, H10, 11-OH), 1.76 – 1.44 (6H, m, H1, H6, H7, H13),
.43 (3H, s, H15), 1.38 – 1.22 (3H, m, H8, H13), 1.08 (3H, s, H18), 0.87
(C15), 11.45 (C17). HR-MS (ESI): Calcd for C31
597.2547; Found: 597.2572.
H39FN
4
O
5
S (M-H ):
=
(
1
4.2.10. 22-(3-amino-2-(4-methoxybenzoyl)-1,2,4-triazole-5-yl)-
thioacetyl)-22-deoxypleuromutilin (16)
1
3
(
3H, d, J = 7.0 Hz, H17), 0.69 (3H, d, J = 7.0 Hz, H16). C NMR (101
MHz, Chloroform-d) δ 216.98 (C3), 167.31 (C21), 165.09, 160.91,
White powder; yield: 26.9%; 1H NMR (600 MHz, Chloroform-d) δ
8.34 – 8.28 (2H, m), 7.00 – 6.96 (2H, m), 6.64 (2H, s), 6.43 (1H, dd, J =
17.4, 11.0 Hz, H19), 5.75 (1H, d, J = 8.5 Hz, H14), 5.26 (1H, dd, J =
11.0, 1.5 Hz, H20), 5.13 (1H, dd, J = 17.4, 1.6 Hz, H20), 3.91 (3H, s,
H32), 3.83 (2H, d, J = 2.3 Hz, H22), 3.33 (1H, t, J = 8.1, 8.1 Hz, H11),
2.34 – 1.99 (5H, m, H2, H4, H10, 11-OH), 1.79 – 1.45 (6H, m, H1, H6,
H7, H8), 1.43 (3H, s, H15), 1.36 – 1.24 (3H, m, H8, H13), 1.08 (3H, s,
1
1
57.59, 138.99 (C19), 134.11, 134.03, 130.79, 123.83, 117.17 (C20),
16.43, 116.22, 74.57 (C11), 69.97 (C14), 58.12 (C4), 45.42 (C9), 44.50
(
C13), 43.92 (C12), 41.84 (C5), 36.70 (C6), 35.98 (C10), 34.45 (C2),
3
1
3.85 (C22), 30.38 (C8), 26.82 (C7), 26.40 (C18), 24.81 (C1), 21.05,
6.65 (C16), 14.82 (C15), 11.45 (C17). HR-MS (ESI): Calcd for
+
C
32
H
42
4
N O
5
S (M-H ): 593.2798; Found: 593.2836.
1
3
H18), 0.87 (3H, d, J = 7.0 Hz, H17), 0.71 (3H, d, J = 7.1 Hz, H16).
C
4
2
.2.7. 22-(3-amino-2-(2-fluoro-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-
2-deoxypleuromutilin (13)
NMR (101 MHz, Chloroform-d) δ 216.97 (C3), 167.40 (C21), 166.48,
163.84, 160.18, 158.87, 138.97 (C19), 134.08, 129.79, 123.31, 117.09
(C20), 114.42, 113.52, 74.56 (C11), 69.98 (C14), 58.14 (C4), 55.53,
45.43 (C9), 44.54 (C13), 43.87 (C12), 41.86 (C5), 36.72 (C6), 35.99
(C10), 34.44 (C2), 33.96 (C22), 30.39 (C8), 26.83 (C7), 26.36 (C18),
White powder; yield: 34.2%; 1H NMR (600 MHz, Chloroform-d) δ
.68 (1H, ddd, J = 8.1, 6.7, 1.7 Hz), 7.60 – 7.53 (1H, m), 7.27 – 7.24 (1H,
7
m), 7.21 – 7.16 (1H, m), 6.76 – 6.60 (2H, m), 6.45 (1H, dd, J = 17.4,
1
5
1.0 Hz, H19), 5.71 (1H, d, J = 8.5 Hz, H14), 5.35 – 5.26 (1H, m, H20),
.17 (1H, dd, J = 17.4, 1.5 Hz, H20), 3.75 (2H, s, H22), 3.35 (1H, dd, J
24.81 (C1), 16.70 (C16), 14.84 (C15), 11.45 (C17). HR-MS (ESI): Calcd
+
for C32
H
42
4
N O
6
S (M-H ): 609.2747; Found: 609.2770.
=
9.7, 6.4 Hz, H11), 2.32 – 2.00 (5H, m, H2, H4, H10, 11-OH), 1.79 –
1
1
.42 (7H, m, H1, H6, H7, H8, H13), 1.40 (3H, s, H15), 1.25 (2H, d, J =
4.2.11. 22-(3-amino-2-(3-methoxybenzoyl)-1,2,4-triazole-5-yl)-
thioacetyl)-22-deoxypleuromutilin (17)
6.0 Hz, H8, H13), 1.14 (3H, s, H18), 0.87 (3H, d, J = 7.0 Hz, H17), 0.64
1
3
White powder; yield: 27.6%; 1H NMR (600 MHz, Chloroform-d) δ
7.82 (1H, dt, J = 7.7, 1.4, 1.4 Hz), 7.74 (1H, p, J = 1.1, 1.1, 1.1, 1.1 Hz),
7.40 (1H, t, J = 8.0, 8.0 Hz), 7.16 (1H, dd, J = 8.2, 2.7 Hz), 6.62 (2H, s),
6.42 (1H, dd, J = 17.5, 11.0 Hz, H19), 5.73 (1H, d, J = 8.5 Hz, H14),
5.27 (1H, dd, J = 11.0, 1.5 Hz, H20), 5.12 (1H, dt, J = 17.4, 1.4, 1.4 Hz,
H20), 3.88 (3H, d, J = 0.9 Hz, H32), 3.82 (2H, s, H22), 3.33 (1H, dd, J =
10.6, 6.5 Hz, H11), 2.36 – 1.92 (5H, m, H2, H4, H10, 11-OH), 1.76 –
1.44 (7H, m, H1, H6, H7, H8, H13), 1.42 (3H, s, H15), 1.36 – 1.11 (2H,
m, H8, H13), 1.07 (3H, s, H18), 0.87 (3H, d, J = 7.0 Hz, H17), 0.69 (3H,
(
3H, d, J = 7.0 Hz, H16). C NMR (101 MHz, Chloroform-d) δ 216.98
(
C3), 167.31 (C21), 165.09, 160.91, 157.59, 138.99 (C19), 134.11,
1
6
34.03, 130.79, 123.83, 117.17 (C20), 116.43, 116.22, 74.57 (C11),
9.97 (C14), 58.12 (C4), 45.42 (C9), 44.50 (C13), 43.92 (C12), 41.84
(
C5), 36.70 (C6), 35.98 (C10), 34.45 (C2), 33.85 (C22), 30.38 (C8),
2
6.82 (C7), 26.40 (C18), 24.81 (C1), 16.65 (C16), 14.82 (C15), 11.45
+
(
C17). HR-MS (ESI): Calcd for C31
H39FN
4
O
5
S (M-H ): 597.2547; Found:
5
97.2554.
1
3
4
2
.2.8. 22-(3-amino-2-(3-fluoro-benzoyl)-1,2,4-triazole-5-yl)-thioacetyl)-
2-deoxypleuromutilin (14)
d, J = 6.9 Hz, H16). C NMR (101 MHz, Chloroform-d) δ 216.97 (C3),
167.31 (C21), 167.20, 160.67, 159.15, 158.63, 138.93 (C19), 132.34,
129.15, 123.90, 119.91, 117.12 (C20), 115.90, 74.56 (C11), 70.00
(C14), 58.12 (C4), 55.48, 45.42 (C9), 44.49 (C13), 43.86 (C12), 41.84
(C5), 36.71 (C6), 35.98 (C10), 34.45 (C2), 33.95 (C22), 30.39 (C8),
White powder; yield: 38.6%; 1H NMR (600 MHz, Chloroform-d) δ
.04 (1H, dt, J = 7.8, 1.2, 1.2 Hz), 7.98 (1H, dt, J = 9.6, 2.1, 2.1 Hz),
.49 (1H, td, J = 8.1, 8.1, 5.5 Hz), 7.33 (1H, td, J = 8.3, 8.3, 2.7 Hz),
.70 (2H, s), 6.44 (1H, dd, J = 17.4, 11.0 Hz, H19), 5.75 (1H, d, J = 8.5
8
7
6
26.82 (C7), 26.35 (C18), 24.81 (C1), 16.68 (C16), 14.80 (C15), 11.45
+
Hz, H14), 5.27 (1H, dd, J = 11.0, 1.5 Hz, H20), 5.14 (1H, dd, J = 17.4,
(C17). HR-MS (ESI): Calcd for C32
609.2731.
H
42
N
4
O
6
S (M-H ): 609.2747; Found:
1
.5 Hz, H20), 3.82 (2H, s, H22), 3.34 (1H, s, H11), 2.35 – 1.99 (6H, m,
8