Y. Li et al.
Bioorganic Chemistry 114 (2021) 105081
2
0: 1) to give compounds B1-B12.
134.23 (s), 131.01 (s), 125.43 (s), 115.49 (s), 115.28 (s), 57.23 (s),
5
5.94 (s), 47.80 (s), 43.98 (s), 32.61 (s), 30.27 (s), 28.64 (s), 27.80 (s),
4
1
.2.1. N-hydroxy-6-[(11aS)-7-chloro-3,11-dioxo-2,3,11,11a-tetrahydro-
26.62 (s), 25.42 (s), 18.66 (s). ESI-HRMS: calcd for C20
H
27
3
N NaO
5
, [M
+
H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]hexanamide (B1)
+ Na] , 412.1848, found 412.1845.
1
H NMR (600 MHz, DMSO) δ 10.33 (s, 1H), 8.65 (s, 1H), 7.63 (s, 1H),
7
9
.54 (d, J = 1.0 Hz, 2H), 4.74 (d, J = 13.8 Hz, 1H), 4.19 (ddd, J = 14.1,
4.2.6. N-hydroxy-8-[(11aS)-7-methoxyl-3,11-dioxo-2,3,11,11a-
.0, 6.8 Hz, 1H), 3.95 (t, J = 7.0 Hz, 1H), 3.86 (d, J = 13.7 Hz, 1H), 3.55
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]octanamide
(
ddd, J = 14.0, 8.9, 5.4 Hz, 1H), 2.44 – 2.37 (m, 1H), 2.33 – 2.26 (m,
(B6)
1
2
1
1
1
2
H), 1.87 (ddd, J = 12.6, 11.5, 6.2 Hz, 3H), 1.48 – 1.39 (m, 4H), 1.19 –
.13 (m, 2H). 13C NMR (151 MHz, DMSO) δ 172.58 (s), 169.41 (s),
66.77 (s), 140.67 (s), 131.79 (s), 131.16 (s), 130.28 (s), 129.89 (s),
26.06 (s), 57.14 (s), 47.73 (s), 43.41 (s), 32.47 (s), 30.16 (s), 27.68 (s),
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.65 (s, 1H), 7.41 (d, J =
8.8 Hz, 1H), 7.08 (d, J = 2.9 Hz, 1H), 7.03 (dd, J = 8.8, 2.9 Hz, 1H), 4.69
(d, J = 13.7 Hz, 1H), 4.21 (ddd, J = 13.7, 9.0, 6.7 Hz, 1H), 3.94 – 3.91
(m, 1H), 3.85 (d, J = 13.6 Hz, 1H), 3.79 (s, 3H), 3.49 (ddd, J = 13.9, 9.0,
6.45 (s), 25.16 (s), 18.68 (s). ESI-HRMS: calcd for C18
3
H22ClN NaO
4
,
5.3 Hz, 1H), 2.41 (dddd, J = 12.5, 10.6, 8.3, 6.6 Hz, 1H), 2.34 – 2.24 (m,
+
13
[
M + Na] , 402.1197, found 402.1190.
2H), 1.94 – 1.80 (m, 3H), 1.46 – 1.35 (m, 4H), 1.21 – 1.12 (m, 6H).
C
NMR (151 MHz, DMSO) δ 172.57 (s), 169.56 (s), 166.74 (s), 158.00 (s),
134.24 (s), 130.99 (s), 125.43 (s), 115.49 (s), 115.27 (s), 57.23 (s),
55.94 (s), 47.82 (s), 43.98 (s), 32.65 (s), 30.27 (s), 28.88 (s), 28.76 (s),
4
1
.2.2. N-hydroxy-7-[(11aS)-7-chloro-3,11-dioxo-2,3,11,11a-tetrahydro-
H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]heptamide (B2)
1
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.63 (s, 1H), 7.63 (s, 1H),
.56 – 7.52 (m, 2H), 4.74 (d, J = 13.8 Hz, 1H), 4.20 (ddd, J = 13.9, 9.1,
.8 Hz, 1H), 3.95 (dd, J = 7.4, 6.6 Hz, 1H), 3.85 (d, J = 13.7 Hz, 1H),
.55 (ddd, J = 14.0, 8.9, 5.4 Hz, 1H), 2.41 (dddd, J = 12.5, 10.5, 8.2, 6.5
27.88 (s), 26.81 (s), 25.46 (s), 18.66 (s). ESI-HRMS: calcd for
+
7
6
3
C
21
H
29
N
3
NaO
5
, [M + Na] , 426.2005, found 426.2001.
4.2.7. N-hydroxy-6-[(11aS)-7-(2-methylphenyl)-3,11-dioxo-2,3,11,11a-
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]hexanamide
(B7)
Hz, 1H), 2.33 – 2.27 (m, 2H), 1.92 – 1.83 (m, 3H), 1.45 – 1.37 (m, 4H),
1
3
1
1
1
2
.18 (d, J = 2.9 Hz, 4H). C NMR (151 MHz, DMSO) δ 172.58 (s),
69.49 (s), 166.78 (s), 140.72 (s), 131.81 (s), 131.15 (s), 130.28 (s),
29.89 (s), 126.07 (s), 57.13 (s), 47.80 (s), 43.42 (s), 32.60 (s), 30.16 (s),
1
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.64 (d, J = 1.4 Hz, 1H),
7.56 (d, J = 9.0 Hz, 1H), 7.47 (s, 1H), 7.45 (d, J = 2.1 Hz, 1H), 7.32 –
7.23 (m, 4H), 4.77 (d, J = 13.8 Hz, 1H), 4.20 (ddd, J = 13.8, 9.3, 6.5 Hz,
1H), 4.03 (dd, J = 7.6, 6.3 Hz, 1H), 3.95 (d, J = 13.7 Hz, 1H), 3.64 (ddd,
J = 14.1, 9.1, 5.2 Hz, 1H), 2.47 – 2.42 (m, 1H), 2.35 – 2.28 (m, 2H), 2.27
(s, 3H), 1.95 – 1.87 (m, 3H), 1.52 – 1.42 (m, 4H), 1.21 (dd, J = 15.5, 7.8
Hz, 2H). 13C NMR (151 MHz, DMSO) δ 172.57 (s), 169.40 (s), 166.92 (s),
140.46 (d, J = 15.8 Hz), 140.15 (s), 135.30 (s), 130.95 (d, J = 8.9 Hz),
130.63 (s), 130.01 (s), 129.56 (s), 128.07 (s), 126.50 (s), 123.84 (s),
57.30 (s), 47.95 (s), 44.02 (s), 32.53 (s), 30.26 (s), 27.90 (s), 26.52 (s),
8.60 (s), 27.84 (s), 26.58 (s), 25.41 (s), 18.68 (s). ESI-HRMS: calcd for
+
C
19
H
3
24ClN NaO
4
, [M + Na] , 416.1353, found 402.1355.
4
1
.2.3. N-hydroxy-8-[(11aS)-7-chloro-3,11-dioxo-2,3,11,11a-tetrahydro-
H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]octanamide (B3)
1
H NMR (600 MHz, DMSO) δ 10.30 (s, 1H), 8.64 (s, 1H), 7.62 (s, 1H),
7
1
1
1
.53 (s, 2H), 4.74 (d, J = 13.8 Hz, 1H), 4.20 (ddd, J = 14.0, 8.9, 6.8 Hz,
H), 3.95 (t, J = 7.0 Hz, 1H), 3.85 (d, J = 13.7 Hz, 1H), 3.54 (ddd, J =
4.1, 8.9, 5.5 Hz, 1H), 2.44 – 2.37 (m, 1H), 2.32 – 2.25 (m, 2H), 1.95 –
25.22 (s), 20.72 (s), 18.59 (s). ESI-HRMS: calcd for C25
H
29
3
N NaO
4
, [M
1
3
+
.82 (m, 3H), 1.43 (dd, J = 13.9, 6.9 Hz, 4H), 1.21 – 1.11 (m, 6H).
C
+ Na] , 458.2056, found 458.2045.
NMR (151 MHz, DMSO) δ 172.56 (s), 169.55 (s), 166.75 (s), 140.71 (s),
1
4
2
31.77 (s), 131.15 (s), 130.25 (s), 129.87 (s), 126.04 (s), 57.12 (s),
4.2.8. N-hydroxy-7-[(11aS)-7-(2-methylphenyl)-3,11-dioxo-2,3,11,11a-
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]heptamide
(B8)
7.81 (s), 43.42 (s), 32.64 (s), 30.15 (s), 28.87 (s), 28.72 (s), 27.92 (s),
6.77 (s), 25.46 (s), 18.67 (s). ESI-HRMS: calcd for C20
3
H26ClN NaO
4
,
+
1
[
M + Na] , 430.1510, found 430.1515.
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.63 (s, 1H), 7.56 (d, J =
8
.9 Hz, 1H), 7.47 (s, 1H), 7.46 – 7.44 (m, 1H), 7.28 (dqd, J = 12.8, 9.0,
4
.2.4. N-hydroxy-6-[(11aS)-7-methoxyl-3,11-dioxo-2,3,11,11a-
1.8 Hz, 4H), 4.76 (d, J = 13.8 Hz, 1H), 4.21 (ddd, J = 13.8, 9.2, 6.6 Hz,
1H), 4.03 (dd, J = 7.6, 6.2 Hz, 1H), 3.94 (d, J = 13.7 Hz, 1H), 3.67 – 3.60
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]hexanamide
(
B4)
(m, 1H), 2.48 – 2.41 (m, 1H), 2.35 – 2.28 (m, 2H), 2.26 (s, 3H), 1.94 –
1
13
H NMR (600 MHz, DMSO) δ 10.30 (s, 1H), 8.64 (s, 1H), 7.42 (d, J =
.9 Hz, 1H), 7.08 (d, J = 2.9 Hz, 1H), 7.03 (dd, J = 8.8, 2.9 Hz, 1H), 4.68
1.86 (m, 3H), 1.46 (ddt, J = 28.8, 14.3, 6.9 Hz, 4H), 1.22 (s, 4H).
C
8
NMR (151 MHz, DMSO) δ 172.58 (s), 169.48 (s), 166.93 (s), 140.56 (s),
140.41 (s), 140.14 (s), 135.30 (s), 130.94 (d, J = 8.2 Hz), 130.62 (s),
130.00 (s), 129.57 (s), 128.07 (s), 126.51 (s), 123.86 (s), 57.30 (s),
48.00 (s), 44.03 (s), 32.61 (s), 30.25 (s), 28.64 (s), 28.06 (s), 26.63 (s),
(
d, J = 13.7 Hz, 1H), 4.19 (ddd, J = 13.8, 9.1, 6.7 Hz, 1H), 3.93 (t, J =
7
9
.1 Hz, 1H), 3.86 (d, J = 13.6 Hz, 1H), 3.79 (s, 3H), 3.48 (ddd, J = 13.9,
.1, 5.2 Hz, 1H), 2.40 (dddd, J = 12.5, 10.6, 8.3, 6.6 Hz, 1H), 2.34 – 2.25
(
m, 2H), 1.92 – 1.81 (m, 3H), 1.48 – 1.36 (m, 4H), 1.16 (dt, J = 14.3, 7.3
25.46 (s), 20.71 (s), 18.59 (s). ESI-HRMS: calcd for C26
H
31
3
N NaO
4
, [M
1
3
+
Hz, 2H). C NMR (151 MHz, DMSO) δ 172.55 (s), 169.42 (s), 166.73 (s),
+ Na] , 472.2212, found 472.2201.
1
5
2
58.01 (s), 134.19 (s), 131.01 (s), 125.42 (s), 115.49 (s), 115.29 (s),
7.23 (s), 55.94 (s), 47.74 (s), 43.97 (s), 32.49 (s), 30.27 (s), 27.65 (s),
4.2.9. N-hydroxy-7-[(11aS)-7-(2-methylphenyl)-3,11-dioxo-2,3,11,11a-
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]octanamide
(B9)
6.49 (s), 25.20 (s), 18.66 (s). ESI-HRMS: calcd for C19
H
25
N
3
NaO
5
, [M
+
+
Na] , 398.1692, found 398.1689.
1
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.65 (s, 1H), 7.55 (d, J =
4
.2.5. N-hydroxy-7-[(11aS)-7-methoxyl-3,11-dioxo-2,3,11,11a-
tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-10(5H)-yl]heptamide
B5)
8.8 Hz, 1H), 7.46 (d, J = 5.6 Hz, 2H), 7.32 – 7.21 (m, 4H), 4.77 (d, J =
13.8 Hz, 1H), 4.25 – 4.19 (m, 1H), 4.04 – 4.00 (m, 1H), 3.94 (d, J = 13.7
Hz, 1H), 3.67 – 3.60 (m, 1H), 2.48 – 2.41 (m, 1H), 2.34 – 2.28 (m, 2H),
2.26 (s, 3H), 1.89 (dt, J = 15.6, 7.6 Hz, 3H), 1.52 – 1.41 (m, 4H), 1.20
(
1
H NMR (600 MHz, DMSO) δ 10.31 (s, 1H), 8.64 (s, 1H), 7.41 (d, J =
.8 Hz, 1H), 7.08 (d, J = 2.9 Hz, 1H), 7.03 (dd, J = 8.8, 2.9 Hz, 1H), 4.68
1
3
8
(dd, J = 15.9, 8.7 Hz, 6H). C NMR (151 MHz, DMSO) δ 172.58 (s),
169.55 (s), 166.92 (s), 140.57 (s), 140.40 (s), 140.15 (s), 135.29 (s),
130.96 (s), 130.91 (s), 130.62 (s), 129.98 (s), 129.55 (s), 128.05 (s),
126.49 (s), 123.85 (s), 57.30 (s), 48.01 (s), 44.03 (s), 32.66 (s), 30.25 (s),
(
d, J = 13.7 Hz, 1H), 4.20 (ddd, J = 13.7, 9.2, 6.7 Hz, 1H), 3.93 (dd, J =
7
1
1
.3, 6.8 Hz, 1H), 3.85 (d, J = 13.6 Hz, 1H), 3.79 (s, 3H), 3.51 – 3.45 (m,
H), 2.40 (dddd, J = 12.5, 10.6, 8.3, 6.6 Hz, 1H), 2.33 – 2.25 (m, 2H),
1
3
.94 – 1.82 (m, 3H), 1.44 – 1.35 (m, 4H), 1.18 (d, J = 3.1 Hz, 4H).
C
28.92 (s), 28.76 (s), 28.13 (s), 26.81 (s), 25.47 (s), 20.67 (s), 18.59 (s).
+
NMR (151 MHz, DMSO) δ 172.56 (s), 169.51 (s), 166.75 (s), 158.01 (s),
ESI-HRMS: calcd for C27
H
34
3
N O
4
, [M+H] , 464.2549, found 464.2555.
1
2