ACCEPTED MANUSCRIPT
Hz, 2H), 2.56 – 2.54 (m, 1H), 2.36 – 2.32 (m, 3H), 2.17 (dd, J = 19.2, 10.2 Hz, 1H), 2.02 (ddd, J = 32.8,
1
1
0
1
5
2
7
7.1, 8.8 Hz, 3H), 1.79 – 1.74 (m, 4H), 1.60 (dd, J = 24.0, 12.0 Hz, 2H), 1.49 – 1.36 (m, 2H), 1.28 –
.19 (m, 3H), 1.24 (d, J = 15.7 Hz, 3H), 1.01 – 0.94 (m, 1H), 0.97 (s, 3H), 0.79 (d, J = 7.0 Hz, 3H),
13
.58 (d, J = 6.7 Hz, 3H); C NMR (101 MHz, DMSO-d ) δ 217.60, 169.26, 168.05, 160.31, 154.45,
6
50.01, 146.54, 141.15, 128.80, 127.18, 126.50, 123.54, 115.61, 104.90, 103.51, 73.03, 70.23, 62.09,
7.69, 54.20, 45.39, 44.50, 44.01, 41.98, 41.77, 36.84, 36.80, 34.44, 33.93, 33.62, 30.55, 29.05, 27.03,
+
4.91, 16.52, 14.96, 11.98; HR-MS (ESI) m/z calcd for C H N O S (M+H) : 728.38402, found:
41
54
5
5
28.38151.
1
4-O-(((4-(2-(4-phenylpiperidin-1-yl)acetamido)-1H-pyrrolo[2,3-d]pyrimidin-6-yl)thio)acetyl)mutilin
1
(
15e): white solid, 60% yield, m. p. : 133.2 – 135.3; H NMR (400 MHz, DMSO-d ) δ 11.83 (s, 1H),
6
1
1
0.13 (s, 1H), 7.24 (d, J = 3.6 Hz, 1H), 6.76 (d, J = 3.5 Hz, 1H), 5.52 (d, J = 8.2 Hz, 1H), 4.98 (d, J =
7.8 Hz, 1H), 4.92 (d, J = 11.2 Hz, 1H), 4.62 (s, 1H), 4.49 (d, J = 5.9 Hz, 1H), 3.99 (dd, J = 20.0, 16.0
Hz, 2H), 3.51 (s, 1H), 3.24 (s, 2H), 2.80 – 2.77 (m, 2H), 2.36 – 2.29 (m, 3H), 2.17 (dd, J = 19.0, 10.7
Hz, 1H), 2.01 (ddd, J = 24.6, 17.4, 8.8 Hz, 3H), 1.78 – 1.75 (m, 2H), 1.65 – 1.55 (m, 2H), 1.55 – 1.51
(
m, 3H), 1.36 (d, J = 13.8 Hz, 1H), 1.31 (s, 3H), 1.24 – 1.20 (m, 3H), 1.02 – 0.98 (m, 1H), 0.96 (s, 3H),
1
3
0
1
5
1
.80 (d, J = 6.9 Hz, 3H), 0.58 (d, J = 6.7 Hz, 3H); C NMR (101 MHz, DMSO-d ) δ 217.62, 169.24,
6
68.04, 160.29, 154.41, 149.96, 141.15, 123.50, 115.60, 104.80, 103.48, 73.04, 70.24, 66.02, 61.79,
7.69, 51.36, 45.39, 44.50, 43.98, 41.97, 36.84, 36.80, 34.83, 34.44, 33.86, 30.55, 29.04, 27.03, 24.91,
+
6.52, 14.95, 11.99; HR-MS (ESI) m/z calcd for C H N O S (M+H) : 668.34763, found: 668.34543.
3
5
50
5
6
1
4-O-(((4-(2-(4-(hydroxymethyl)piperidin-1-yl)acetamido)-1H-pyrrolo[2,3-d]pyrimidin-6-yl)thio)acety
1
l)mutilin (15f): white solid, 56% yield, m. p. : 119.5 – 121.0; H NMR (400 MHz, CDCl ) δ 11.83 (s,
3
1
H), 10.09 (s, 1H), 7.24 (d, J = 3.3Hz, 1H), 6.77 (d, J = 3.3Hz, 1H), 5.52 (d, J = 8.2 Hz, 1H), 4.98 (dd,
J = 17.8, 1.6 Hz, 1H), 4.92 (dd, J = 11.2, 1.6 Hz, 1H), 4.49 (d, J = 5.7 Hz, 1H), 4.45 (brs, 1H), 3.99 (q,
J = 16.2 Hz, 2H), 3.28 (d, J = 6.2 Hz, 2H), 3.24 (s, 2H), 2.90 (d, J = 10.9 Hz, 2H), 2.37 (s, 1H), 2.20 –
2
3
.15 (m, 3H), 2.02 (ddd, J = 36.0, 16.0, 8.0 Hz, 3H), 1.70 – 1.58 (m, 4H), 1.48 –1.34 (m, 3H), 1.31 (s,
H), 1.28 – 1.18 (m, 5H), 1.02 – 0.98 (m, 1H), 0.96 (s, 3H), 0.80 (d, J = 6.9 Hz, 3H), 0.58 (d, J = 6.7
1
3
Hz, 3H); C NMR (101 MHz, DMSO-d ) δ 217.61, 169.27, 168.03, 160.29, 154.43, 149.93, 141.14,
6
1
4
23.51, 115.60, 104.81, 103.51, 99.99, 73.03, 70.23, 66.34, 62.20, 57.69, 53.66, 45.40, 44.50, 44.01,
1.97, 38.32, 36.79, 34.44, 33.89, 30.55, 29.32, 29.04, 27.03, 24.91, 16.51, 14.96, 11.99; HR-MS (ESI)
+
m/z calcd for C H N O S (M+H) : 682.36328, found: 682.36091.
3
6
52
5
6
1
4-O-(((4-(2-([1,4'-bipiperidin]-1'-yl)acetamido)-1H-pyrrolo[2,3-d]pyrimidin-6-yl)thio)acetyl)mutilin
1
(
15g): yellow solid, 68% yield, m. p. : 123.9 – 125.7; H NMR (400 MHz, DMSO-d ) δ 11.85 (s, 1H),
6
1
8
0.17 (s, 1H), 8.26 (s, 1H), 7.24 (dd, J = 3.3, 2.3 Hz, 1H), 6.75 (dd, J = 3.5, 1.7 Hz, 1H), 5.52 (d, J =
.3 Hz, 1H), 4.98 (dd, J = 17.8, 1.6 Hz, 1H), 4.92 (dd, J = 11.2, 1.6 Hz, 1H), 4.00 (dd, J = 20.0, 16.2
Hz, 2H), 3.39 (d, J = 5.7 Hz, 1H), 2.98 (d, J = 10.9 Hz, 2H), 2.73 (m, 4H), 2.57 (t, J = 11.5 Hz, 1H),
2
1
.37 (s, 1H), 2.24 (t, J = 11.8 Hz, 2H), 2.16 (t, J = 11.8 Hz, 1H), 2.02 (ddd, J = 32.0, 17.5, 8.8 Hz, 3H),
.82 (d, J = 11.1 Hz, 2H), 1.66 – 1.60 (m, 8H), 1.43 (d, J = 5.0 Hz, 3H), 1.37 (d, J = 13.8 Hz, 1H), 1.31
(
s, 3H), 1.25 – 1.21 (m, 3H), 1.01 (d, J = 4.3 Hz, 1H), 0.96 (s, 3H), 0.80 (d, J = 6.9 Hz, 3H), 0.57 (d, J
1
3
=
6.7 Hz, 3H); C NMR (101 MHz, DMSO-d ) δ 217.61, 169.14, 168.04, 164.63, 160.28, 154.40,
6
1
50.01, 141.14, 123.52, 115.60, 104.86, 103.44, 73.02, 70.24, 62.15, 61.45, 57.70, 52.85, 49.79, 45.40,