PAPER
Sulfides of Cinchona Alkaloids
1181
1
3
13
C NMR (125 MHz, CDCl ): d = 26.6, 27.2, 27.7, 39.4, 47.3, 47.5,
C NMR (75 MHz, CDCl ): d = 27.9, 28.3, 28.8, 39.5, 41.4, 51.8,
3
3
4
1
1
9.3, 55.3, 55.7, 61.4, 100.8, 110.5, 114.4, 120.6, 120.9, 121.4,
23.5, 129.2, 129.5, 131.6, 136.0, 141.4, 144.3, 145.7, 147.5, 157.5,
59.5.
55.6, 56.0, 57.7, 101.0, 114.6, 120.0, 121.0, 127.2, 127.6, 128.6,
128.7, 131.9, 135.4, 141.8, 144.8, 147.2, 151.4, 157.7.
Anal. Calcd for C H N S: C, 74.96; H, 6.78; N, 6.72; S, 7.70.
2
6
28
2
Anal. Calcd for C H N O S: C, 72.61; H, 6.77; N, 6.27; S, 7.18.
Found: C, 75.10; H, 6.72; N, 6.69; S, 7.67.
27
30
2
2
Found: C, 72.46; H, 6.79; N, 6.25; S, 7.21
(
1S,3R,4S,8S,9R)-10,11-Dihydro-6¢-methoxy-9-phenylsulfanyl-
9
-(2-Butoxycarbonylphenylsulfanyl)-epi-quinidine
cinchonan (9-Phenylsulfanyldihydroquinine, 9-PhS-DHQN, 5c)
[
9-(2-BuO CC H S)-epi-QD, 2l]
Yield: 68%; oil; [a] +105.3 (c 0.98, CH Cl ); R = 0.20
2
6
4
D
2
2
f
Yield: 67%; yellow oil, which solidified later; [a] +159.1 (c 0.90,
CH Cl ); R = 0.26 (EtOAc–hexane, 9:1).
(CHCl –t-BuOMe, 1:1).
D
3
2
2
f
IR (film): 2932, 1621, 1587, 1508, 1472, 1260, 1088, 1033, 834,
–
1
IR (KBr): 3071, 2934, 1717, 1618, 1582, 1506, 1463, 1359, 1246,
1
751, 693 cm .
–
1
111, 1056, 912, 848, 748 cm .
1
H NMR (300 MHz, CDCl ): d = 0.93 (t, J = 7.2 Hz, 3 H, CH ),
3
3
1
H NMR (300 MHz, CDCl ): d = 0.97 (t, J = 7.3 Hz, 3 H, CH ),
1.34–1.50 (m, 4 H), 1.62–1.70 (m, 2 H), 1.87 (s, 1 H), 2.31–2.46 (m,
3 H), 2.72–2.83 (m, 1 H), 2.93–3.04 (m, 1 H), 3.20–3.26 (m, 1 H),
3
3
1
2
.09–1.20 (m, 2 H), 1.40–1.62 (m, 5 H), 1.69–1.76 (m, 2 H), 2.29–
.33 (m, 1 H), 2.97–3.13 (m, 3 H), 3.26–3.33 (m, 2 H), 3.88 (s, 3 H,
3.86 (s, 3 H, OCH ), 4.69 (d, J = 9.2, 1 H, H-9), 7.01–7.32 (m, 8 H,
3
OCH ), 4.33 (t, J = 6.3 Hz, 2 H, OCH ), 5.10 (d, J = 10.5 Hz, 1 H,
SC H + ArH), 7.97 (d, J = 9.2 Hz, 1 H, ArH), 8.56 (s, 1 H, ArH).
3
2
6
5
CH =), 5.23 (d, J = 17.2 Hz, 1 H, CH =), 5.62 (d, J = 10.8 Hz, 1 H,
13
2
2
C NMR (75 MHz, CDCl ): d = 12.2, 26.1, 27.8, 28.7, 28.8, 37.3,
3
H-9), 5.87–5.98 (m, 1 H, CH=), 6.76–6.97 (m, 3 H, SC H ), 7.20–
6
5
4
1
1.5, 52.1, 55.5, 57.8, 59.9, 101.0, 119.9, 120.9, 127.6, 128.6,
28.7, 131.5, 131.9, 135.3, 144.8, 145.0, 147.3, 157.6.
7
.26 (m, 1 H, ArH), 7.35 (s, 1 H, ArH), 7.42 (d, J = 7.6 Hz, 1 H,
SC H ), 7.70 (d, J = 4.3 Hz, 1 H, ArH), 7.85 (d, J = 9.1 Hz, 1 H,
6
5
Anal. Calcd for C H N OS: C, 74.60; H, 7.23; N, 6.69; S, 7.66.
Found: C, 74.27; H, 6.91; N, 6.58; S, 7.65.
ArH), 8.71 (d, J = 4.3 Hz, 1 H, ArH).
26 30
2
1
3
C NMR (125 MHz, CDCl ): d = 13.8, 19.3, 26.6, 27.0, 27.8, 30.7,
3
3
1
1
9.4, 46.9, 49.2, 49.6, 55.4, 61.3, 65.2, 100.5, 114.4, 120.6, 121.9,
27.1, 128.9, 129.6, 130.3, 131.4, 134.0, 135.3, 136.2, 141.0, 144.4,
45.6, 147.6, 157.7, 167.7.
(
(
1S,3R,4S,8R,9S)-6¢-Methoxy-9-phenylsulfanylcinchonan
9-Phenylsulfanylquinidine, 9-PhS-QD, 5e)
Yield: 63%; oil; [a] –22.5 (c 0.94, CH Cl ); R = 0.19
(CHCl –t-BuOMe, 1:1).
3
D
2
2
f
Anal. Calcd for C H N O S: C, 72.06; H, 7.02; N, 5.42; S, 6.21.
31
36
2
3
Found: C, 71.85; H, 6.99; N, 5.38; S, 6.24.
IR (film): 2935, 1621, 1587, 1508, 1472, 1432, 1244, 1032, 913,
–
1
8
31, 750, 693 cm .
(
1S,3R,4S,8S,9R)-9-Phenylsulfanylcinchonan (9-Phenylsulfa-
1
H NMR (300 MHz, CDCl ): d = 1.56–1.71 (m, 3 H), 1.94–2.11 (m,
nylcinchonidine, 9-PhS-CD, 5a)
3
1
H), 2.16–2.26 (m, 1 H), 2.61–2.81 (m, 5 H), 3.22–3.31 (m, 1 H),
Yield: 75%; oil; [a] +19.0 (c 0.84, CH Cl ); R = 0.24
D
2
2
f
3
2
.85 (s, 3 H, OCH ), 4.78 (d, J = 9.2 Hz, 1 H, H-9), 5.00–5.14 (m,
(
CHCl –t-BuOMe, 1:1).
3
3
H, CH =), 5.94–6.05 (m, 1 H, CH=), 6.90–7.21 (m, 7 H, SC H +
2
6
5
IR (film): 2938, 2862, 1636, 1588, 1508, 1470, 1263, 1025, 913,
ArH), 7.30 (dd, J = 9.2, 2.4 Hz, 1 H, ArH), 7.97 (d, J = 9.2 Hz, 1 H,
ArH), 8.58 (s, 1 H, ArH).
–1
7
66, 693 cm .
1
H NMR (300 MHz, CDCl ): d = 1.51–1.62 (m, 3 H), 1.85 (s, 1 H),
13
3
C NMR (125 MHz, CDCl ): d = 26.6, 27.3, 28.3, 39.6, 47.9, 49.4,
3
2
2
.17–2.21 (m, 1 H), 2.32–2.40 (m, 2 H), 2.52–2.57 (m, 1 H), 2.66–
.78 (m, 1 H), 2.90–2.98 (m, 1 H), 3.16–3.21 (m, 1 H), 4.78 (d,
5
1
1.3, 55.4, 58.1, 100.9, 114.6, 119.7, 121.1, 127.8, 128.4, 128.7,
31.5, 131.9, 134.7, 140.8, 144.8, 145.4, 147.3, 157.6.
J = 9.2 Hz, 1 H, H-9), 4.98–5.04 (m, 2 H, CH =), 5.85–5.90 (m, 1
2
+
MS (EI, 70 eV): m/z = 416 (14, [M ]), 337 (12), 307 (100), 306 (16),
H, CH=), 6.81–7.19 (m, 6 H, SC H + ArH), 7.39–7.48 (m, 1 H,
6
5
2
74 (12), 196 (34), 186 (21), 154 (22), 108 (17), 81 (22), 55 (21).
ArH), 7.58 (t, J = 7.4 Hz, 1 H, ArH), 7.89–7.91 (m, 1 H, ArH), 8.01
(
1
d, J = 8.4 Hz, 1 H, ArH), 8.63 (d, J = 3.6 Hz, 1 H, ArH).
Anal. Calcd for C H N S: C, 74.96; H, 6.78; N, 6.72; S, 7.70.
Found: C, 74.72; H, 6.81; N, 6.69; S, 7.73.
2
6
28
2
3
C NMR (75 MHz, CDCl ): d = 26.9, 27.3, 28.1, 38.6, 40.3, 50.6,
3
5
1
5.0, 56.7, 113.4, 118.6, 121.3, 125.2, 125.6, 127.5, 127.6, 129.5,
29.8, 130.5, 134.6, 140.9, 145.3, 147.1, 148.6.
(
1S,3R,4S,8R,9S)-10,11-Dihydro-6¢-methoxy-9-phenylsulfanyl-
cinchonan (9-Phenylsulfanyldihydroquinidine, 9-PhS-DHQD,
f)
Yield: 70%; oil; [a] –15.9 (c 0.88, CH Cl ); R = 0.19
Anal. Calcd for C H N OS: C, 77.68; H, 6.78; N, 7.24; S, 8.30.
Found: C, 77.40; H, 6.81; N, 7.21; S, 8.33.
2
5
26
2
5
D
2
2
f
(
CHCl –t-BuOMe, 1:1).
3
(
(
1S,3R,4S,8S,9R)-6¢-Methoxy-9-phenylsulfanylcinchonan
9-Phenylsulfanylquinine, 9-PhS-QN, 5b)
IR (film): 2931, 2869, 1621, 1587, 1507, 1472, 1227, 1086, 1033,
–
1
8
46, 830, 747, 693 cm .
Yield: 65%; oil, which solidified later; [a] +62.5 (c 0.32, CH Cl );
R = 0.23 (CHCl –t-BuOMe, 1:1).
D
2
2
1
f
3
H NMR (300 MHz, CDCl ): d = 0.90 (t, J = 7.2 Hz, 3 H, CH ),
3
3
1
.32–1.50 (m, 4 H), 1.55–1.70 (m, 1 H), 1.80 (s, 1 H), 1.89–1.92 (m,
1 H), 2.00–2.08 (m, 1 H), 2.33–2.39 (m, 1 H), 2.66–2.77 (m, 3 H),
.20–3.25 (m, 1 H), 3.87 (s, 3 H, OCH ), 4.79 (d, J = 8.0 Hz, 1 H,
IR (film): 2936, 1621, 1586, 1505, 1471, 1360, 1224, 1086, 1026,
9
–
1
11, 833, 748, 692 cm .
3
1
3
H NMR (300 MHz, CDCl ): d = 1.56–1.69 (m, 4 H), 1.87 (s, 1 H),
3
H-9), 6.98–7.20 (m, 7 H, SC H + ArH), 7.30 (dd, J = 9.2, 2.6 Hz,
6
5
2
.22 (s, 1 H), 2.35–2.39 (m, 2 H), 2.57–2.60 (m, 1 H), 2.74 (br s, 1
1
H, ArH), 7.96 (d, J = 9.2 Hz, 1 H, ArH), 8.57 (s, 1 H, ArH).
H), 2.88–2.98 (m, 1 H), 3.19–3.26 (m, 1 H), 3.82 (s, 3 H, OCH3),
4
7
1
3
C NMR (75 MHz, CDCl ): d = 12.0, 25.8, 26.7, 27.4, 28.2, 37.6,
.99–5.05 (m, 3 H, CH =, H-9), 5.83–5.94 (m, 1 H, CH=), 6.83–
3
2
4
1
9.5, 49.9, 51.3, 55.5, 58.3, 101.1, 119.7, 120.9, 127.8, 128.3,
28.7, 131.5, 131.9, 134.6, 144.8, 145.6, 147.4, 157.5.
.28 (m, 8 H, SC H , ArH), 7.91 (d, J = 9.2 Hz, 1 H, ArH), 8.50 (d,
6
5
J = 3.4 Hz, 1 H, ArH).
Anal. Calcd for C H N OS: C, 74.60; H, 7.23; N, 6.69; S, 7.66.
2
6
30
2
Found: C, 74.26; H, 7.30; N, 6.71; S, 7.50.
Synthesis 2006, No. 7, 1176–1182 © Thieme Stuttgart · New York