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[a]2D0 +19 (c 1.0, EtOH); 1H NMR (400 MHz, CDCl3) d 5.69 (s, 1H),
5.29 (s, 1H), 4.20 (d, J ¼ 10.2 Hz, 1H), 3.73 (s, 4H), 3.56–3.24 (m,
7H), 3.01 (t, J ¼ 12.6 Hz, 1H), 2.96–2.80 (m, 1H), 2.65–2.46 (m,
5H), 2.34 (ddd, J ¼ 18.2, 11.5, 4.5 Hz, 3H), 2.01 (dt, J ¼ 14.3,
4.1 Hz, 2H), 1.88 (dq, J ¼ 10.2, 3.3 Hz, 1H), 1.73 (ddt, J ¼ 13.5,
6.3, 3.3 Hz, 2H), 1.62–1.19 (m, 18H), 1.10–0.99 (m, 1H), 0.96 (d, J
¼ 6.1 Hz, 3H), 0.80 (d, J ¼ 7.1 Hz, 3H); 13C NMR (101 MHz,
CDCl3) d 171.3, 167.9, 153.6, 104.3, 97.5, 92.1, 91.2, 80.3, 60.6,
58.3, 58.3, 54.9, 54.8, 52.8, 51.9, 51.6, 45.8, 37.6, 36.3, 34.3, 29.8,
29.5, 29.2, 26.9, 26.7, 26.1, 24.9, 23.5, 21.7, 20.4, 14.3, 13.6; IR
(KBr) n/cmꢁ1: 2934, 2869, 1744, 1638, 1438, 1301, 1259, 1041,
848, 746; HRMS m/z: calcd for C34H55ClN3O9S 716.3342, found
716.3337 [M + H]+.
hexyl)piperazin-1-yl)-5-methoxyfuran-2(5H)-one (12d). Hybrid 12d
was formed in 80% yield (98.8% HPLC purity) as a yellow solid.
mp 78.2–79.2 ꢂC; [a]D20 +6 (c 1.0, EtOH); 1H NMR (400 MHz,
CDCl3) d 5.74 (s, 1H), 5.29 (s, 1H), 4.16 (dd, J ¼ 29.7, 8.7 Hz, 1H),
3.90–3.79 (m, 1H), 3.77 (s, 4H), 3.75–3.63 (m, 1H), 3.48 (s, 1H),
3.47–3.36 (m, 3H), 3.33 (d, J ¼ 14.4 Hz, 1H), 3.02 (t, J ¼ 12.8 Hz,
1H), 2.95–2.87 (m, 1H), 2.64–2.54 (m, 1H), 2.58–2.51 (m, 4H),
2.44–2.35 (m, 2H), 2.32 (dd, J ¼ 14.2, 4.3 Hz, 1H), 2.08–1.95 (m,
2H), 1.89 (ddd, J ¼ 14.0, 6.8, 3.4 Hz, 1H), 1.73 (ddt, J ¼ 13.5, 6.2,
3.4 Hz, 2H), 1.61–1.44 (m, 6H), 1.42–1.17 (m, 12H), 1.09–0.98
(m, 1H), 0.96 (d, J ¼ 6.2 Hz, 3H), 0.80 (d, J ¼ 7.1 Hz, 3H); 13C
NMR (101 MHz, CDCl3) d 171.3, 168.7, 156.6, 104.3, 97.8, 92.1,
91.2, 80.3, 64.0, 60.7, 60.5, 58.4, 53.0, 51.9, 51.6, 47.6, 45.8, 37.6,
36.3, 34.3, 29.4, 29.2, 27.0, 26.8, 26.5, 26.1, 24.9, 23.5, 21.7, 20.4,
15.1, 13.6; IR (KBr) n/cmꢁ1: 2934, 2892, 2872, 1762, 1636, 1454,
1303, 1127, 974, 646; HRMS m/z: calcd for C34H55BrN3O9S
760.2837, found 760.2833 [M + H]+.
4.2.9.2. (5S)-3-Chloro-4-(4-(6-((2S)-1,1-dioxido-4-
((3R,5aS,6R,8aS,9R,10R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-
epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)thiomorpholin-2-yl)
hexyl)piperazin-1-yl)-5-(((1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexyl)oxy)furan-2(5H)-one (12b). Hybrid 12b was formed in
82% yield (98.6% HPLC purity) as a yellow solid. mp 75.6–
76.1 ꢂC; [a]D20 ꢁ2 (c 1.0, EtOH); 1H NMR (400 MHz, CDCl3) d 6.73
(s, 0.2H), 5.78 (s, 0.8H), 5.29 (s, 1H), 4.20 (d, J ¼ 10.2 Hz, 1H),
3.82–3.59 (m, 4H), 3.59–3.27 (m, 5H), 3.01 (t, J ¼ 12.5 Hz, 1H),
2.95–2.87 (m, 1H), 2.61–2.29 (m, 8H), 2.28–2.12 (m, 1H), 2.02 (q,
J ¼ 8.3, 6.5 Hz, 3H), 1.89 (ddd, J ¼ 14.3, 7.0, 3.6 Hz, 2H), 1.71
(tdd, J ¼ 17.9, 8.0, 3.7 Hz, 5H), 1.51 (tdd, J ¼ 16.6, 11.5, 6.8 Hz,
5H), 1.43–1.22 (m, 13H), 1.13 (q, J ¼ 12.2 Hz, 1H), 0.93 (dt, J ¼
15.2, 7.2 Hz, 11H), 0.78 (dq, J ¼ 12.1, 6.8, 5.5 Hz, 7H); 13C NMR
(101 MHz, CDCl3) d 168.4, 155.0, 104.3, 97.3, 92.1, 91.2, 87.6,
81.0, 80.3, 60.7, 58.5, 52.9, 51.9, 51.6, 48.2, 47.7, 45.8, 42.6, 40.5,
37.6, 36.3, 34.3, 34.0, 31.8, 29.8, 29.5, 29.2, 27.1, 26.8, 26.1, 25.2,
4.2.9.5. (5S)-3-Bromo-4-(4-(6-((2S)-1,1-dioxido-4-
((3R,5aS,6R,8aS,9R,10R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-
epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)thiomorpholin-2-yl)
hexyl)piperazin-1-yl)-5-(((1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexyl)oxy)furan-2(5H)-one (12e). Hybrid 12e was formed in
78% yield as a yellow gum. [a]2D0 ꢁ3 (c 1.0, EtOH); 1H NMR (400
MHz, CDCl3) d 5.79 (s, 1H), 5.28 (s, 1H), 4.19 (d, J ¼ 10.2 Hz, 1H),
3.86–3.50 (m, 4H), 3.47–3.28 (m, 4H), 3.01 (t, J ¼ 12.6 Hz, 1H),
2.90 (d, J ¼ 11.5 Hz, 1H), 2.53 (ddt, J ¼ 21.4, 6.8, 3.9 Hz, 4H),
2.43–2.28 (m, 4H), 2.25–2.13 (m, 1H), 2.04–1.84 (m, 3H), 1.75–
1.63 (m, 4H), 1.59–1.43 (m, 6H), 1.35 (d, J ¼ 12.6 Hz, 10H), 1.28–
1.05 (m, 6H), 1.03–0.85 (m, 12H), 0.80–0.73 (m, 7H); 13C NMR
(100 MHz, CDCl3) d 168.7, 157.6, 104.2, 98.2, 92.0, 91.1, 80.7,
80.2, 73.8, 58.4, 52.8, 51.8, 51.5, 48.2, 47.8, 45.7, 42.5, 37.5, 36.2,
34.2, 34.0, 31.7, 31.5, 29.4, 29.1, 27.0, 26.7, 26.0, 25.1, 24.8, 23.4,
24.9, 23.5, 22.8, 22.4, 21.7, 21.3, 20.4, 15.9, 13.6; IR (KBr) n/cmꢁ1
:
2933, 2888, 2870, 1760, 1634, 1455, 1302, 1126, 974, 879, 746;
HRMS m/z: calcd for C43H71ClN3O9S 840.4594, found 840.4596
[M + H]+.
22.8, 22.3, 21.6, 21.2, 20.3, 19.4, 15.8, 13.5; IR (KBr) n/cmꢁ1
2932, 1761, 1635, 1454, 1302, 1126, 934, 879; HRMS m/z: calcd
for C43H71BrN3O9S 884.4089, found 884.4088 [M + H]+.
4.2.9.6. (5S)-3-Bromo-4-(4-(6-((S)-1,1-dioxido-4-
:
4.2.9.3. 3-Chloro-4-(4-(6-((S)-1,1-dioxido-4-
((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3H-
3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)thiomorpholin-2-
yl)hexyl)piperazin-1-yl)-5-(((2S)-1,7,7-trimethylbicyclo[2.2.1]hep-
tan-2-yl)oxy)furan-2(5H)-one (12c). Hybrid 12c was formed in
80% yield (96.9% HPLC purity) as a yellow gum. [a]2D0 +10 (c 1.0,
EtOH); 1H NMR (400 MHz, CDCl3) d 6.73 (s, 0.7H), 5.72 (s, 0.2H),
5.29 (s, 1H), 4.19 (d, J ¼ 10.3 Hz, 1H), 3.74 (s, 1H), 3.56–3.27 (m,
8H), 3.02 (t, J ¼ 12.5 Hz, 1H), 2.90 (d, J ¼ 11.1 Hz, 1H), 2.68–2.17
(m, 8H), 2.05–1.98 (m, 2H), 1.98–1.83 (m, 1H), 1.80–1.67 (m,
4H), 1.62–1.42 (m, 4H), 1.43–1.19 (m, 16H), 1.11–1.00 (m, 1H),
0.96 (d, J ¼ 6.3 Hz, 5H), 0.92–0.84 (m, 9H), 0.80 (d, J ¼ 7.1 Hz,
3H), 0.61 (t, J ¼ 7.1 Hz, 1H); 13C NMR (101 MHz, CDCl3) d 162.9,
161.8, 132.3, 129.1, 104.3, 92.1, 91.2, 83.5, 80.3, 60.7, 58.5, 53.0,
52.0, 51.6, 49.2, 48.1, 45.8, 44.9, 37.6, 36.4, 34.3, 32.1, 29.8, 29.4,
29.2, 28.5, 28.1, 27.2, 27.1, 26.8, 26.5, 26.1, 24.9, 24.4, 23.5, 22.8,
21.8, 20.4, 19.8, 19.0, 13.6; IR (KBr) n/cmꢁ1: 2932, 2887, 2867,
1758, 1628, 1449, 1377, 1302, 1127, 1040, 960, 847, 744; HRMS
m/z: calcd for C43H69ClN3O9S 838.4438, found 838.4432 [M +
H]+.
((3R,5aS,6R,8aS,9R,10R,12R,12aR)-3,6,9-trimethyldecahydro-3H-
3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)thiomorpholin-2-
yl)hexyl)piperazin-1-yl)-5-(((2S)-1,7,7-trimethylbicyclo[2.2.1]hep-
tan-2-yl)oxy)furan-2(5H)-one (12f). Hybrid 12f was formed in 81%
ꢂ
yield (96.8% HPLC purity) as a yellow solid. mp 77.9–78.9 C;
[a]2D0 +11 (c 1.0, EtOH); 1H NMR (400 MHz, CDCl3) d 6.95 (s,
0.3H), 5.73 (d, J ¼ 10.1 Hz, 0.4H), 5.29 (s, 1H), 4.20 (d, J ¼
10.3 Hz, 1H), 3.79–3.73 (m, 2H), 3.67 (s, 1H), 3.54–3.24 (m, 6H),
3.02 (t, J ¼ 12.7 Hz, 1H), 2.91 (d, J ¼ 11.3 Hz, 1H), 2.63–2.25 (m,
8H), 2.03 (d, J ¼ 6.9 Hz, 3H), 1.94–1.83 (m, 2H), 1.79–1.65 (m,
4H), 1.58 (dd, J ¼ 13.1, 4.5 Hz, 1H), 1.53–1.46 (m, 7H), 1.36 (d, J
¼ 11.3 Hz, 8H), 1.33–1.21 (m, 5H), 1.05 (ddt, J ¼ 18.1, 13.4,
5.9 Hz, 2H), 0.96 (d, J ¼ 6.3 Hz, 3H), 0.87 (dd, J ¼ 11.0, 5.2 Hz,
8H), 0.81 (t, J ¼ 10.0 Hz, 3H); 13C NMR (101 MHz, CDCl3)
d 163.3, 162.1, 136.2, 118.9, 104.3, 92.0, 91.1, 83.5, 80.2, 60.7,
58.5, 58.4, 53.0, 52.4, 51.9, 51.6, 49.5, 49.2, 48.0, 47.6, 45.7, 45.0,
44.9, 37.6, 36.3, 34.3, 29.4, 29.1, 28.1, 28.0, 27.1, 26.8, 26.0, 24.9,
23.4, 21.7, 20.4, 19.8, 18.9, 14.2, 13.6; IR (KBr) n/cmꢁ1: 2932,
2890, 2871, 1760, 1628, 1453, 1304, 1126, 879, 744; HRMS m/z:
calcd for C43H69BrN3O9S 882.3932, found 882.3921 [M + H]+.
4.2.9.4. 3-Bromo-4-(4-(6-((2S)-1,1-dioxido-4-
((3R,5aS,6R,8aS,9R,10R,12aR)-3,6,9-trimethyldecahydro-3H-3,12-
epoxy[1,2]dioxepino[4,3-i]isochromen-10-yl)thiomorpholin-2-yl)
© 2021 The Author(s). Published by the Royal Society of Chemistry
RSC Adv., 2021, 11, 18333–18341 | 18339