K. Tani et al. / Bioorg. Med. Chem. 10 (2002) 1093–1106
1103
(br, 1H), 3.55 (dd, J=10.2, 2.4 Hz, 1H), 2.74 (ddd,
J=18.4, 7.4, 1.0 Hz, 1H), 2.50–1.50 (m, 19H), 2.31 (t,
J=7.3 Hz, 2H), 1.50–1.20 (m, 3H), 0.94 (t, J=6.9 Hz,
3H).
(m, 7H), 4.10–3.98 (m, 1H), 3.56 (d, J=9 Hz, 1H), 2.72
(dd, J=18, 7Hz, 1H), 2.47–1.15 (m, 23H), 2.30 (t, J=7
Hz, 2H), 0.90 (t, J=7Hz, 3H); MS (EI, Pos) m/z 388
(MÀH2O)+, 37 0 (MÀ2H2O)+, 266, 248.
To a stirred solution of the more polar product (330 mg,
0.813 mmol) in 3 mL of ethanol and 30 mL of phos-
phate buffer (pH=7.4), 800 mL (1880 units) of aqueous
(3.2 mol/L ammonium sulfate) suspension of porcine
liver esterase (PLE) was added and stirring was con-
tinued for 6 h at room temperature. The resulting mix-
ture was diluted with EtOAc. The organic layer was
washed with water and brine, dried over anhydrous
magnesium sulfate and concentrated in vacuo. The
residue was purified by column chromatography on
silica gel to yield 4b (275 mg, 86%) as a pale yellow
viscous oil. Optical rotation [a]2D5=À69.4 (c 0.79,
EtOH); TLC Rf 0.36 (EtOAc/n-hexane/AcOH, 16/8/1);
IR (neat) 3369, 2956, 2932, 2872, 1741, 1709, 1456,
1431, 1407, 1340, 1240, 1158, 1074, 969, 734 cmÀ1; MS
(APCI, Neg, 40v) m/z 391 (MÀH)À, 37
(MÀH2OÀH)À; 1H NMR (200 MHz, CDCl3) d 5.68
(ddd, J=15.4, 8.2, 6.0 Hz, 1H), 5.50–5.25 (m, 3H),
5.20–4.00 (br, 3H), 4.13–3.96 (m, 1H), 3.59 (dd, J=10.4,
2.2 Hz, 1H), 2.73 (ddd, J=18.6, 7.4, 1.0 Hz, 1H), 2.50–
1.20 (m, 23H), 0.94 (t, J=6.7Hz, 3H); 13C NMR
(125 MHz, CDCl3) d 214.77, 177.95, 132.41, 131.85,
130.79, 126.70, 75.96, 72.13, 54.63, 53.79, 46.37, 45.25,
38.44, 34.50, 33.19, 27.30, 27.04, 26.34, 24.97, 24.51, 17.42,
15.14, 14.83. Anal. calcd for C23H36O5; C, 7 0.38; H, 9.24;
Found; C, 69.97; H, 9.37.
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-20-ethyl-
PGE2 (4d). Yellow oil; TLC Rf 0.73 (EtOAc/AcOH, 50/
1); IR (neat) 3392, 2931, 1740, 1406, 1244, 1159, 1075
cmÀ1; 1H NMR (200 MHz, CDCl3) d 5.76–5.61 (m, 1H),
5.49–5.32 (m, 3H), 4.80–4.20 (bs, 3H), 4.11–3.98 (m,
1H), 3.59 (dd, J=10, 1 Hz, 1H), 2.73 (dd, J=18, 8 Hz,
1H), 2.45–1.15 (m, 25H), 2.35 (t, J=7Hz, 2H), 0.90 (t,
J=7Hz, 3H); MS (FAB, Pos) m/z 421 (M+H)+, 403
(M+HÀH2O)+, 385, 367.
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-19-methyl-
PGE2 (4e). Pale yellow oil; TLC Rf 0.24 (n-hexane/
EtOAc/AcOH, 1/2/0.03); IR (neat) 3369, 2952, 1741,
;
1709, 1407, 1241, 1158, 1075, 968 cmÀ1 1H NMR
(200 MHz, CDCl3) d 5.72 (ddd, J=15.2, 8.0, 5.8 Hz,
1H), 5.55–5.25 (m, 3H), 5.20–4.20 (br, 3H), 4.14–3.98
(m, 1H), 3.68 (dd, J=10.0, 2.0 Hz, 1H), 2.74 (ddd,
J=18.0, 7.2, 1.0 Hz, 1H), 2.50–1.50 (m, 20H), 1.55 (dd,
J=14.2, 7.2 Hz, 1H), 1.33 (dd, J=14.2, 6.4 Hz, 1H),
0.92 (d, J=6.4 Hz, 6H); MS (FAB, Pos. m/z 389
(M+HÀH2O)+, 371, 353.
3
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-!-dinor-
18-cyclopropylPGE2 (4f). Pale yellow oil; TLC Rf 0.26
(n-hexane/EtOAc/AcOH, 1/2/0.03); IR (neat) 3369,
1
2932, 1741, 1430, 1241, 1158, 1075, 1019, 968 cmÀ1; H
NMR (200 MHz, CDCl3) d 6.00–4.00 (br, 3H), 5.70
(ddd, J=15.4, 7.8, 5.6 Hz, 1H), 5.50–5.25 (m, 3H),
4.14–3.96 (m, 1H), 3.73 (dd, J=10.0, 2.0 Hz, 1H), 2.74
(dd, J=18.4, 7.6 Hz, 1H), 2.50–1.60 (m, 19H), 1.50 (dd,
J=14.2, 6.8 Hz, 1H), 1.37(dd, J=14.2, 6.3 Hz, 1H),
0.90–0.70 (m, 1H), 0.60–0.45 (m, 2H), 0.17–0.05 (m,
2H); MS (FAB, Pos.) m/z 405 (M+H)+, 387
(M+HÀH2O)+, 369, 351.
Compound 9 was synthesized from the less polar pro-
duct by the same procedure described above. Pale yel-
low viscous oil; TLC Rf 0.41 (EtOAc/n-hexane/AcOH,
16/8/1); IR (neat) 3418, 2932, 1734, 1406, 1241, 1158,
1075, 971 cmÀ1; MS (APCI, Neg, 40v) m/z 391
(MÀH)À, 37 3 (MÀH2OÀH)À; 1H NMR (200 MHz,
CDCl3) d 5.74 (dt, J=15.0, 6.0 Hz, 1H), 5.55–5.25 (m,
3H), 4.08 (q, J=7.5 Hz, 1H), 3.64 (dd, J=10.5, 2.5 Hz,
1H), 2.75 (dd, J=18.0, 7.5 Hz, 1H), 2.50–2.20 (m, 7H),
2.20–1.20 (m, 18H), 0.94 (t, J=7.0 Hz, 3H). The com-
pounds 4a and 4c–o were synthesized from 19a and 19c–o
and 25, respectively, according to the same procedure
used for preparation of the compound 4b described
above.
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-!-nor-
18,19-didehydroPGE2 (4g). Colorless oil; TLC Rf 0.32
(EtOAc/AcOH, 50/1); IR (neat) 3392, 2942, 1732, 1636,
;
1412, 1242, 1160, 1074, 970, 914 cmÀ1 1H NMR
(200 MHz, CDCl3) d 5.93 (dd, J=17.2, 10.6 Hz, 1H),
5.65 (ddd, J=15.2, 8.2, 5.6 Hz, 1H), 5.28–5.15 (m, 3H),
5.25 (dd, J=10.6, 1.4 Hz, 1H), 5.16 (dd, J=17.2, 1.4
Hz, 1H), 5.10–4.10 (br, 3H), 4.08–3.95 (m, 1H), 3.63
(dd, J=10.6, 2.0 Hz, 1H), 2.70 (ddd, J=19.2, 7.6, 1.1
Hz, 1H), 2.42–1.60 (m, 19H); MS (FAB, Pos) m/z 377
(M+H)+, 359 (M+HÀH2O)+, 341, 323.
(16S) - 15 - Deoxy - 16 - hydroxy - 17,17 - trimethylene - !-
norPGE2 (4a). Colorless oil; TLC Rf 0.39 (EtOAc/
AcOH, 50/1); IR (neat) 3391, 2936, 1740, 1714, 1461,
1431, 1406, 1339, 1241, 1159, 1073, 1028, 969, 914, 875,
734, 649 cmÀ1 1H NMR (200 MHz, CDCl3) d 5.71
;
(ddd, J=15, 8, 6 Hz, 1H), 5.49–5.29 (m, 3H), 5.20–4.40
(br, 3H), 4.11–3.98 (m, 1H), 3.60 (dd, J=10, 2 Hz, 1H),
2.73 (ddd, J=18, 7, 1 Hz, 1H), 2.45–1.35 (m, 19H),
2.33 (t, J=7Hz, 2H), 0.92 (t, J=7Hz, 3H); MS
(FAB, Pos) m/z 379 (M+H)+, 361 (M+HÀH2O)+,
343, 325.
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-19,20-di-
dehydroPGE2 (4h). Colorless oil; TLC Rf 0.21 (n-hex-
ane/EtOAc/AcOH, 1/2/0.03); IR (neat) 3392, 2933,
1740, 1434, 1241, 1159, 1075, 998, 969, 914, 733 cmÀ1
;
1H NMR (200 MHz, CDCl3) d 5.94 (ddt, J=17.2, 10.2,
7.2 Hz, 1H), 5.66 (ddd, J=15.2, 8.0, 5.6 Hz, 1H), 5.53–
5.25 (m, 3H), 5.30–4.50 (br, 3H), 5.20–5.00 (m, 2H),
4.12–3.96 (m, 1H), 3.58 (dd, J=10.2, 1.8 Hz, 1H),
2.72 (dd, J=18.2, 7.2 Hz, 1H), 2.50–1.60 (m, 21H);
MS (EI, Pos) m/z 372 (MÀH2O)+, 354 (MÀ2H2O)+,
248, 230.
(16S)-15-Deoxy-16-hydroxy-17,17-trimethylene-20-methyl-
PGE2 (4c). Pale yellow oil; TLC Rf 0.67(EtOAc/AcOH,
50/1); IR (neat) 3392, 2931, 1732, 1405, 1242, 1159,
1
1075 cmÀ1; H NMR (200 MHz, CDCl3) d 5.90–4.80