1270
H. Kikuchi et al. / European Journal of Medicinal Chemistry 46 (2011) 1263e1273
chloroformeMeOH (9:1) to give 21a (22.7 mg, 0.114 mmol, 59%).
Data for 21a: colorless oil; 1H NMR (400 MHz, CDCl3)
6.86 (1H, dd,
8.5 Hz); 13C NMR (100 MHz, CD3OD)
d 170.8, 151.9, 121.1, 74.3 (2C),
d
38.3, 37.7 (2C), 24.0, 6.6 (2C); EIMS m/z 211 [M]þ, 183, 167, 155, 137
(base), 119, 109, 95, 81; HREIMS m/z 211.1230 [M]þ (211.1207 calcd.
for C11H17NO3)
J ¼ 14.9, 8.3 Hz), 6.17 (1H, d, J ¼ 14.9 Hz), 4.48 (2H, br.s), 4.09e4.16
(2H, m), 3.06 (3H, s), 2.98 (3H, s), 2.59e2.67 (1H, m), 2.10e2.20 (2H,
m), 1.64e1.75 (2H, m); 13C NMR (100 MHz, CDCl3)
d 167.0, 150.7,
118.1, 73.4 (2C), 37.8, 37.5, 37.0 (2C), 35.9; EIMS m/z 199 [M]þ, 155,
136, 126 (base); HREIMS m/z 199.1212 [M]þ (199.1207 calcd. for
C10H17NO3).
3.1.17.7. Data for (E)-3-(c-3,c-4-dihydroxycyclopent-r-1-yl)propeno-
hydroxamic acid (21h). Colorless oil; 1H NMR (400 MHz, CD3OD)
d
1.55e1.63 (2H, m), 2.07e2.18 (2H, m), 2.63e2.73 (1H, m),
In the similar procedure, compounds 21b (yield 51%), 21c (91%),
21d (86%), 21e (70%), 21f (69%), 21g (94%), 21h (95%) and 21i (71%)
were synthesized from 20bei, respectively. Compounds 26a (yield
77%), 26b (78%), 26c (79%), 26d (54%), 26e (92%), 26f (66%), 26g
(75%), 26h (78%), 26i (66%), 26j (65%) and 26k (34%) were also
synthesized from 25aek, respectively.
3.97e4.04 (2H, m), 5.80 (1H, d, J ¼ 15.5 Hz), 6.91 (1H, dd, J ¼ 15.5,
8.2 Hz); 13C NMR (100 MHz, CD3OD)
d 166.2, 151.7, 117.8, 74.4 (2C),
38.3, 37.8 (2C); EIMS m/z 187 [M]þ, 155, 137 (base); HREIMS m/z
187.0822 [M]þ (187.0844 calcd. for C8H13NO4).
3.1.17.8. Data for (3-[(E)-c-3,c-4-Dihydroxycyclopent-r-1-yl]prope-
noyl)piperidine (21i). Colorless oil; 1H NMR (400 MHz, CD3OD)
3.1.17.1. Data for (E)-N-phenyl-3-(c-3,c-4-dihydroxycyclopent-r-1-yl)
d
6.75 (1H, dd, J ¼ 15.1, 8.5 Hz), 6.35 (1H, dd, J ¼ 15.1, 1.0 Hz),
propenamide (21b). Colorless amorphous solid; 1H NMR (400 MHz,
3.95e4.00 (2H, m), 3.55e3.61 (4H, m), 2.63e2.74 (1H, m),
CD3OD)
d
7.58 (2H, d, J ¼ 7.2 Hz), 7.30 (2H, t, J ¼ 7.2 Hz), 7.08 (1H, t,
2.08e2.17 (2H, m), 1.67e1.73 (2H, m), 1.53e1.65 (6H, m); 13C NMR
J ¼ 7.2 Hz), 6.94 (1H, dd, J ¼ 15.1, 8.5 Hz), 6.05 (1H, d, J ¼ 15.1 Hz),
3.97e4.09 (2H, m), 2.66e2.76 (1H, m), 2.11e2.22 (2H, m), 1.59e1.70
(100 MHz, CD3OD) d 167.8, 152.0, 119.8, 74.7 (2C), 48.2, 44.6, 38.7
(2C), 38.2, 28.0, 27.1, 25.8; EIMS m/z 239 [M]þ, 195, 166, 138 (base);
HREIMS m/z 239.1508 [M]þ (239.1520 calcd. for C13H21NO3).
(2H, m); 13C NMR (100 MHz, CD3OD)
d 166.9, 151.1,140.0, 129.8 (2C),
125.2, 123.4 (2C),121.4, 74.4 (2C), 38.5, 37.7 (2C); EIMS m/z 247 [M]þ
(base), 204,146, 137, 93; HREIMS m/z 247.1196 [M]þ (247.1207 calcd.
for C14H17NO3).
3.1.17.9. Data for (E)-N-(4-chlorophenyl)-3-(c-3,c-4-dihydroxycyclo-
pent-r-1-yl)propenamide (26a). Colorless amorphous solid; 1H
NMR (400 MHz, CD3OD)
d
7.60 (2H, d, J ¼ 8.7 Hz), 7.29 (2H, d,
3.1.17.2. Data for (E)-3-(c-3,c-4-dihydroxycyclopent-r-1-yl)propena-
J ¼ 8.7 Hz), 6.94 (1H, dd, J ¼ 15.3, 8.5 Hz), 6.05 (1H, dd, J ¼ 15.3,
1.1 Hz), 3.97e4.03 (2H, m), 2.63e2.75 (1H, m), 2.09e2.19 (2H, m),
1.61 (2H, ddd, J ¼ 13.3, 8.8, 5.6 Hz); 13C NMR (100 MHz, CD3OD)
mide (21c). Colorless oil; 1H NMR (400 MHz, CD3OD)
d 6.80 (1H, dd,
J ¼ 15.4, 8.5 Hz), 5.88 (1H, dd, J ¼ 15.4, 1.1 Hz), 3.94e3.99 (2H, m),
2.59e2.68 (1H, m), 2.07e2.16 (2H, m), 1.53e1.62 (2H, m); 13C NMR
d
166.8, 151.6, 138.8, 130.0, 129.8 (2C), 123.1, 121.4 (2C), 74.4 (2C),
(100 MHz, CD3OD)
d
172.1, 154.0, 120.5, 74.3 (2C), 38.2, 37.8 (2C);
38.4 (2C), 37.7; EIMS m/z 283 [Mþ2]þ, 281 [M]þ, 238, 169, 137, 127
(base); HREIMS m/z 281.0821 [M]þ (281.0818 calcd. for
C14H16NO3Cl).
EIMS m/z 153 [M]þ, 137, 119 (base), 72; HREIMS m/z 153.0788 [M]þ
(153.0789 calcd. for C8H11NO2).
3.1.17.3. Data for (E)-N-methyl-3-(c-3,c-4-dihydroxycyclopent-r-1-
3.1.17.10. Data for (E)-N-(3,4-dichlorophenyl)-3-(c-3,c-4-dihydrox-
yl)propenamide (21d). Colorless oil; 1H NMR (400 MHz, CD3OD)
ycyclopent-r-1-yl)propenamide (26b). Colorless amorphous solid;
d
6.66 (1H, dd, J ¼ 15.4, 8.3 Hz), 5.73 (1H, dd, J ¼ 15.4, 1.2 Hz),
1H NMR (400 MHz, CD3OD)
J ¼ 8.8, 2.3 Hz), 7.42 (1H, d, J ¼ 8.8 Hz), 6.96 (1H, dd, J ¼ 15.2, 8.2 Hz),
6.00 (1H, dd, J ¼ 15.2,1.1 Hz), 3.96e4.02 (2H, m), 2.63e2.75 (1H, m),
2.08e2.17 (2H, m), 1.55e1.65 (2H, m); 13C NMR (100 MHz, CD3OD)
d
7.95 (1H, d, J ¼ 2.3 Hz), 7.46 (1H, dd,
3.84e3.92 (2H, m), 2.67 (3H, s), 1.96e2.06 (2H, m), 1.43e1.52
(2H, m); 13C NMR (100 MHz, CD3OD)
d 169.9, 151.0, 121.6, 74.4 (2C),
38.4, 37.7 (2C), 26.7; EIMS m/z 185 [M]þ, 141, 112 (base); HREIMS m/
z 185.1042 [M]þ (185.1051 calcd. for C9H15NO3).
d
166.8, 152.1, 140.1, 133.3, 131.5, 127.7, 122.9, 122.5, 120.6, 74.4 (2C),
38.4 (2C), 37.7; EIMS m/z 319 [Mþ4]þ, 317 [Mþ2]þ, 315 [M]þ, 272,
203, 161 (base), 137; HREIMS m/z 315.0412 [M]þ (315.0428 calcd.
for C14H15NO3Cl2).
3.1.17.4. Data for (E)-N-ethyl-3-(c-3,c-4-dihydroxycyclopent-r-1-yl)
propenamide (21e). Colorless oil; 1H NMR (400 MHz, CD3OD)
d 6.86
(1H, dd, J ¼ 15.4, 8.5 Hz), 5.89 (1H, d, J ¼ 15.4 Hz), 3.98e4.07 (2H,
m), 3.34 (2H, q, J ¼ 7.3 Hz), 2.62e2.73 (1H, m), 2.09e2.21 (2H, m),
1.55e1.67 (2H, m), 1.15 (3H, t, J ¼ 7.2 Hz),; 13C NMR (100 MHz,
3.1.17.11. Data for (E)-N-(4-fluorophenyl)-3-(c-3,c-4-dihydroxycyclo-
pent-r-1-yl)propenamide (26c). Colorless amorphous solid; 1H
NMR (400 MHz, CD3OD) d 7.55e7.61 (2H, m), 6.99e7.04 (2H, m),
CD3OD)
d
169.2, 151.5, 121.5, 74.4 (2C), 38.4, 37.8 (2C), 35.9, 14.5;
EIMS m/z 199 [M]þ, 155, 126 (base); HREIMS m/z 199.1193 [M]þ
(199.1207 calcd. for C10H17NO3).
6.94 (1H, dd, J ¼ 15.3, 7.3 Hz), 6.02 (1H, dd, J ¼ 15.4, 1.4 Hz),
3.98e4.04 (2H, m), 2.62e2.74 (1H, m), 2.12e2.20 (2H, m), 1.58e1.67
(2H, m); 13C NMR (100 MHz, CD3OD)
d
166.5, 160.3 (d, J ¼ 242 Hz),
3.1.17.5. Data for (E)-N-butyl-3-(c-3,c-4-dihydroxycyclopent-r-1-yl)
150.7, 134.3 (d, J ¼ 3 Hz), 123.0, 122.8 (2C, d, J ¼ 8 Hz), 116.0 (2C, d,
J ¼ 23 Hz), 74.0 (2C), 38.2 (2C), 37.3; EIMS m/z 265 [M]þ, 222,167, 91
(base); HREIMS m/z 265.1090 [M]þ (265.1113 calcd. for
C14H16NO3F).
propenamide (21f). Colorless oil; 1H NMR (400 MHz, CD3OD)
d 6.84
(1H, dd, J ¼ 15.5, 8.3 Hz), 5.90 (1H, d, J ¼ 15.5 Hz), 3.95e4.03 (2H,
m), 3.27 (2H, t, J ¼ 7.2 Hz), 2.62e2.71 (1H, m), 2.07e2.18 (2H, m),
1.52e1.67 (4H, m), 1.37 (2H, sextet, J ¼ 7.2 Hz), 0.94 (3H, t,
J ¼ 7.2 Hz); 13C NMR (100 MHz, CD3OD)
d
169.3, 151.4, 121.6, 74.4
3.1.17.12. Data for (E)-N-[4-(trifluoromethyl)phenyl]-3-(c-3,c-4-
dihydroxycyclopent-r-1-yl)propenamide (26d). Colorless amor-
(2C), 40.7, 39.1, 37.8 (2C), 32.2, 21.1, 14.0; EIMS m/z 227 [M]þ, 212,
183, 154, 137 (base); HREIMS m/z 227.1505 [M]þ (227.1520 calcd. for
C12H21NO3).
phous solid; 1H NMR (400 MHz, CD3OD)
d
7.80 (2H, d, J ¼ 8.5 Hz),
7.59 (2H, d, J ¼ 8.5 Hz), 6.99 (1H, dd, J ¼ 15.3, 7.7 Hz), 6.06 (1H, dd,
J ¼ 15.3, 1.4 Hz), 3.97e4.03 (2H, m), 2.64e2.76 (1H, m), 2.10e2.19
3.1.17.6. Data for (E)-N-cyclopropyl-3-(c-3,c-4-dihydroxycyclopent-
(2H, m), 1.57e1.67 (2H, m); 13C NMR (100 MHz, CD3OD)
d 167.0,
r-1-yl)propenamide (21g). Colorless oil; 1H NMR (400 MHz, CD3OD)
152.1, 143.6, 127.0 (2C, q, J ¼ 4 Hz), 126.5 (q, J ¼ 33 Hz), 125.7 (q,
J ¼ 270 Hz), 123.0 (2C), 120.9, 74.4 (2C), 38.3 (2C), 37.7; EIMS m/z
315 [M]þ, 296, 279 (base), 272, 203, 188, 116, 137, 109; HREIMS m/z
315.1070 [M]þ (315.1081 calcd. for C15H16NO3F3).
d
0.60e0.67 (2H, m), 0.79e0.84 (2H, m), 1.57e1.66 (2H, m),
2.08e2.17 (2H, m), 2.63e2.74 (1H, m), 2.79e2.85 (1H, m),
3.96e4.05 (2H, m), 5.90 (1H, d, J ¼ 14.8 Hz), 6.90 (1H, dd, J ¼ 14.8,