Asymmetric Synthesis and Antitumor Activity of Spiro Oxadiazole Derivatives
5.09 (d, J=5.1 Hz, 1H, H-3); 13C NMR (101 MHz,
CDCl3) δ: 13.8 (CH3), 20.6 (COCH3), 22.0 (COCH3),
22.2 (CH2), 25.0 (CH2), 25.4 (CH2), 31.0 (CH2), 68.5
(C-6), 72.7 (C-5), 72.8 (C-1), 79.9 (C-4), 83.7 (C-3),
103.7 (C-2), 158.4 (C-7), 167.2 (C=O), 170.3 (C=O);
HRMS (ESI) calcd for C16H25N2O6 [M+H+] 341.1707,
found 341.1719.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-benzyl-3a,5,6,6a-tetra-
hydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-[1,3,4]oxa-
diazol]-6-yl acetate (2e): White solid; m.p. 81-82 ℃;
1H NMR (400 MHz, CDCl3) δ: 2.14 (s, 3H, COCH3),
2.25 (s, 3H, COCH3), 3.63 (t, J=8.3 Hz, 1H, H-6b),
3.73 (s, 2H, CH2), 3.89 (d, J=10.3 Hz, 1H, H-1b), 4.04
(dd, J=8.3, 7.1 Hz, 1H, H-6a), 4.43 (d, J=10.3 Hz, 1H,
H-1a), 4.87 (t, J=5.2 Hz, 1H, H-4), 4.96 (ddd, J=9.6,
7.0, 5.2 Hz, 1H, H-5), 5.12 (d, J=5.2 Hz, 1H, H-3),
7.31-7.39 (m, 5H, Ar-H); 13C NMR (101 MHz,CDCl3)
δ: 20.6 (COCH3), 22.0 (COCH3), 32.0 (CH2), 68.4 (C-6),
72.6 (C-5), 72.6 (C-1), 79.8 (C-4), 83.6 (C-3), 104.3
(C-2), 127.5, 128.7, 128.8, 133.3 (Ar-C), 156.8 (C-7),
167.5 (C=O), 170.3 (C=O); HRMS (ESI) calcd for
C18H21N2O6 [M+H+] 361.1394, found 361.1397.
COCH3), 3.92 (t, J=8.7 Hz, 1H, H-6b), 4.06 (d, J=
10.4 Hz, 1H, H-1b), 4.23 (t, J=7.6 Hz, 1H, H-6a), 4.53
(d, J=10.4 Hz, 1H, H-1a), 4.96 (t, J=5.0 Hz, 1H, H-4),
5.01-5.09 (m, 1H, H-5), 5.21 (d, J=5.1 Hz, 1H, H-3),
7.46 (t, J=7.4 Hz, 2H, Ar-H), 7.52 (d, J=7.0 Hz, 1H,
Ar-H), 7.87 (d, J=7.5 Hz, 2H, Ar-H); 13C NMR (101
MHz, CDCl3) δ: 20.7 (COCH3), 22.1 (COCH3), 68.7
(C-6), 72.7 (C-5), 72.9 (C-1), 80.0 (C-4), 83.8 (C-3),
104.6 (C-2), 124.1 (Ar-C), 126.9 (Ar-C), 128.7 (Ar-C),
131.8 (Ar-C), 154.8 (C-7), 167.7 (C=O), 170.3 (C=O);
HRMS (ESI) calcd for C17H19N2O6 [M+H+] 346.1165,
found 347.1239.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-(p-tolyl)-3a,5,6,6a-tetra-
hydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-[1,3,4]oxa-
diazol]-6-yl acetate (2i): White foam; m.p. 114 -
1
115 ℃; H NMR (400 MHz, CDCl3) δ: 2.18 (s, 3H,
COCH3), 2.34 (s, 3H, COCH3), 2.42 (s, 3H, CH3), 3.91
(t, J=8.7 Hz, 1H, H-6b), 4.05 (d, J=10.3 Hz, 1H,
H-1b), 4.23 (t, J=7.3 Hz, 1H, H-6a), 4.52 (d, J=10.3
Hz, 1H, H-1a), 4.95 (t, J=4.3 Hz, 1H, H-4), 5.00-5.08
(m, 1H, H-5), 5.21 (d, J=4.5 Hz, 1H, H-3), 7.75 (d, J=
7.2 Hz, 2H, Ar-H), 7.26 (d, J=7.5 Hz, 2H, Ar-H); 13C
NMR (101 MHz, CDCl3) δ: 20.7 (COCH3), 21.7 (CH3),
22.2 (COCH3), 68.6 (C-6), 72.7 (C-5), 72.9 (C-1), 79.9
(C-4), 83.7 (C-3), 104.4 (C-2), 121.2, 126.9, 129.4,
142.4 (Ar-C), 155.0 (C-7), 167.6 (C=O), 170.3 (C=O);
HRMS (ESI) calcd for C18H21N2O6 [M+H+] 361.1394,
found 361.1390.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-(2-chlorobenzyl)-
3a,5,6,6a-tetrahydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-
[1,3,4]oxadiazol]-6-yl acetate (2f): Off-white solid; m.p.
83-85 ℃; 1H NMR (400 MHz, CDCl3) δ: 2.07 (s, 3H,
COCH3), 2.21 (s, 3H, COCH3), 3.57-3.61 (m 1H,
H-6b), 3.77-3.95 (m, 3H, H-1b CH2), 3.98-4.04 (m,
1H, H-6a), 4.42 (d, J=10.3 Hz, 1H, H-1a), 4.84 (d, J=
4.3 Hz, 1H, H-4), 4.87-4.93 (m, 1H, H-5), 5.11 (d, J=
4.4 Hz, 1H, H-3), 7.20-7.29 (m, 2H, Ar-H), 7.34-
7.40 (m, 2H, Ar-H); 13C NMR (101 MHz, CDCl3) δ:
20.6 (COCH3), 22.0 (COCH3), 29.7 (CH2), 68.4 (C-6),
72.6 (C-1, C-5), 79.7 (C-3), 83.5 (C-4), 104.4 (C-2),
127.0, 129.0, 129.6, 130.7, 131.4, 134.2 (Ar-C), 155.8
(C-7), 167.5 (C=O), 170.3 (C=O); HRMS (ESI) calcd
for C18H20ClN2O6 [M+H+] 395.1004, found 395.1010.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-(furan-2-yl)-3a,5,6,6a-
tetrahydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-[1,3,4]-
oxadiazol]-6-yl acetate (2g): White foam; m.p. 127-
(3R,3aS,6R,6aR)-3'-Acetyl-5'-(4-methoxyphenyl)-
3a,5,6,6a-tetrahydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-
[1,3,4]oxadiazol]-6-yl acetate (2j): White foam; m.p.
1
146-147 ℃; H NMR (400 MHz, CDCl3) δ: 2.18 (s,
3H, COCH3), 2.34 (s, 3H, COCH3), 3.87 (s, 3H), 3.91 (d,
J=8.9 Hz, 1H, H-6b), 4.05 (d, J=10.3 Hz, 1H, H-1b),
4.23 (t, J=7.6 Hz, 1H, H-6a), 4.52 (d, J=10.3 Hz, 1H,
H-1a), 4.95 (t, J=4.9 Hz, 1H, H-4), 5.04 (dd, J=15.0,
6.4 Hz, 1H, H-5), 5.20 (d, J=5.0 Hz, 1H, H-3), 6.95 (d,
J=8.5 Hz, 2H, Ar-H), 7.80 (d, J=8.5 Hz, 2H, Ar-H);
13C NMR (101 MHz, CDCl3) δ: 20.7 (COCH3), 22.1
(COCH3), 55.4 (OCH3), 68.6 (C-6), 72.7 (C-5), 72.9
(C-1), 80.0 (C-4), 83.7 (C-3), 104.2 (C-2), 114.2, 116.3,
128.7, 154.8, 162.4 (Ar-C), 167.6 (C=O), 170.4 (C=
O); HRMS (ESI) calcd for C18H21N2O7 [M+H+ ]:
377.1343, found 377.1349.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-(2-methoxyphenyl)-
3a,5,6,6a-tetrahydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-
[1,3,4]oxadiazol]-6-yl acetate (2k): White solid; m.p.
149-150 ℃; [α]2D0 +145.7 (c 0.50, EtOAc); 1H
NMR (400 MHz, CDCl3) δ: 2.17 (s, 3H, COCH3), 2.37
(s, 3H, COCH3), 3.86-3.97 (m, 4H, H-6b, OCH3), 4.05
(d, J=10.2 Hz, 1H, H-1b), 4.23 (t, J=7.3 Hz, 1H,
H-6a), 4.52 (d, J=10.2 Hz, 1H, H-1a), 4.96 (s, 1H, H-4),
5.00-5.08 (m, 1H, H-5), 5.21 (d, J=4.2 Hz, 1H, H-3),
7.00-7.08 (m, 2H, Ar-H), 7.49 (t, J=7.7 Hz, 1H,
Ar-H), 7.78 (d, J=7.4 Hz, 1H, Ar-H); 13C NMR (101
MHz, CDCl3) δ: 20.7 (COCH3), 22.2 (COCH3), 56.0
(OCH3), 68.5 (C-6), 72.8 (C-5), 73.0 (C-1), 80.0 (C-4),
83.8 (C-3), 103.2 (C-2), 111.8, 112.9, 120.6, 130.2,
1
128 ℃; H NMR (400 MHz, CDCl3) δ: 2.18 (s, 3H,
COCH3), 2.36 (s, 3H, COCH3), 3.88 (t, J=8.7 Hz, 1H,
H-6b), 4.07 (d, J=10.5 Hz, 1H, 1b), 4.23 (t, J=7.6 Hz,
1H, H-6a), 4.51 (d, J=10.5 Hz, 1H, H-1a), 4.96 (t, J=
5.1 Hz, 1H, H-4), 5.01-5.08 (m, 1H, H-5), 5.19 (d, J=
5.1 Hz, 1H, H-3), 6.57 (dd, J=3.4, 1.7 Hz, 1H, C4H3O),
7.00 (d, J=3.2 Hz, 1H, C4H3O), 7.62 (s, 1H, C4H3O);
13C NMR (101 MHz, CDCl3) δ: 20.7 (COCH3), 22.2
(COCH3), 68.7 (C-6), 72.67 (C-5), 72.9 (C-1), 80.0
(C-4), 83.7 (C-3), 104.7 (C-2), 111.9 (C4H3O), 115.0
(C4H3O), 139.3 (C4H3O), 146.0 (C4H3O), 148.0 (C-7),
167.8 (C=O), 170.3 (C=O); HRMS (ESI) calcd for
C15H17N2O7 [M+H+] 337.1030, found 337.1033.
(3R,3aS,6R,6aR)-3'-Acetyl-5'-phenyl-3a,5,6,6a-tetra-
hydro-2H,3'H-spiro[furo[3,2-b]furan-3,2'-[1,3,4]oxa-
diazol]-6-yl acetate (2h): White solid; m.p. 122 -
1
124 ℃; [α]2D0 +155.3 (c 0.50, EtOAc); H NMR (400
MHz, CDCl3) δ: 2.18 (s, 3H, COCH3), 2.36 (s, 3H,
Chin. J. Chem. 2017, XX, 1—8
© 2017 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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