D. F. Taber, Q. Jiang / Tetrahedron 56 (2000) 5991±5994
5993
sodium metal/benzophenone ketyl under dry nitrogen.
Dichloromethane (CH2Cl2) and toluene were distilled
from calcium hydride under dry nitrogen. All reaction
mixtures stirred magnetically, unless otherwise noted.
(5Z,8R,11S,12S,13E,15R)-11,15-Bis(tert-butyldimethyl-
silyloxy)-9-oxoprosta-5,13-dienoic acid (6). To a stirred
solution of hydroxy acid 8 (48.5 mg, 0.083 mmol) in dry
CH2Cl2 (10 mL) was added Dess±Martin periodinate
(70 mg, 0.17 mmol). The reaction mixture was stirred for
20 h at rt under N2 and was then chromatographed directly
to give the keto acid 6 (46 mg, 95%) as a colorless oil, TLC
Rf0.45 (EtOAc/MeOH/AcOH95/5/0.1); [a]D242.4
(c1.53, CHCl3); FAB MS m/z (rel. intensity) 603
(M11Na, 100), 563 (6), 449 (17), 431 (10), 373 (11), 317
(12), 299 (17), 264 (41); IR (®lm) 2955, 2929, 2857, 1745,
Ethyl (5Z,8R,9R,11S,12S,13E,15R)-9-acetoxy-11,15-bis-
(tert-butyldimethylsilyloxy)prosta-5,13-dienoate (7). To
a stirred solution of diol 5 (47 mg, 0.11 mmol), imidazole
(45 mg, 0.66 mmol), and a catalytic amount of DMAP in
dry CH2Cl2 (10 mL) was added TBDMSCl (83 mg,
0.55 mmol). The reaction mixture was stirred for 24 h at rt
under N2 and was then partitioned between CH2Cl2 and,
sequentially, saturated aqueous NH4Cl and brine. The
combined organic extract was dried (Na2SO4) and concen-
trated. The residue was chromatographed to afford the
acetate 7 (59 mg, 82%) as a colorless oil, TLC Rf0.74
(petroleum ether/MTBE4/1); [a]D214.3 (c1.48,
CHCl3); FAB MS m/z (rel intensity) 675 (M11Na, 100),
595 (52), 521 (18), 461 (92), 389 (21), 329 (88); IR (®lm)
2956, 2930, 2857, 1738, 1463, 1362, 1248, 1078, 971, 836,
1709, 1458, 1362, 1255, 1070, 1006, 968, 836, 776 cm21
;
1H NMR d 5.59 (dd, 1H, J6.4 and 15.2 Hz), 5.34±5.43 (m,
2H), 5.11 (dd, 1H, J10.2 and 15.2 Hz), 4.23 (d, 1H,
J5.2 Hz), 4.02 (dd, 1H, J5.8 and 12.0 Hz), 2.93 (t, 1H,
J8.4 Hz), 2.67±2.72 (m, 1H), 2.46±2.50 (m, 1H), 2.43
(dd, 1H, J5.2 and 19.0 Hz), 2.33 (t, 2H, J7.9 Hz), 2.24
(d, 1H, J19.0 Hz), 2.04±2.13 (m, 2H), 1.80±1.87 (m, 1H),
1.65±1.72 (m, 2H), 1.25±1.49 (m, 8H), 0.87 (s, 21H), 0.08
(s, 3H), 0.06 (s, 3H), 0.02 (s, 3H), 0.00 (s, 3H); 13C NMR d
up 217.7, 179.3, 45.3, 38.2, 33.3, 31.7, 26.6, 24.8, 24.5,
22.9, 22.6, 18.2, 18.0; down 138.1, 129.7, 127.9, 125.5,
73.2, 72.7, 51.9, 50.3, 25.8, 25.7, 14.0, 24.3, 24.7, 24.8,
24.9; FAB HRMS calcd for C32H60O5Si2Na 603.3877,
found 603.3860.
1
775 cm21; H NMR d 5.49 (dd, 1H, J6.3 and 15.2 Hz),
5.30±5.40 (m, 2H), 5.25 (dd, 1H, J9.8 and 15.2 Hz), 4.76
(dt, 1H, J4.4 and 11.6 Hz), 4.10 (q, 2H, J7.2 Hz), 4.02
(dd, 1H, J5.9 and 12.1 Hz), 3.96 (dt, 1H, J2.9 and
6.0 Hz), 2.60±2.63 (m, 1H), 2.53 (dddd, 1H, J6.4, 8.4
and 14.8 Hz), 2.35 (quint, 1H, J7.5 Hz), 2.27 (t, 2H,
J7.5 Hz), 2.02 (s, 3H), 1.92±2.08 (m, 4H), 1.62±1.72
(m, 2H), 1.24±1.55 (m, 9H), 1.24 (t, 3H, J7.1 Hz), 0.87
(s, 9H), 0.86 (s, 12H), 0.03 (s, 3H), 0.02 (s, 3H), 0.01 (s,
6H); 13C NMR d up 173.5, 171.1, 60.1, 41.2, 38.4, 33.7,
31.8, 26.7, 26.5, 24.9, 24.8, 22.6, 18.2, 18.0; down
137.0, 129.4, 128.6, 126.6, 78.3, 76.2, 73.3, 53.4,
46.4, 25.8, 25.7, 21.2, 14.2, 14.0, 24.3, 24.70, 24.72,
24.78; FAB HRMS calcd for C36H68O6Si2Na 675.4452,
found 675.4424.
ent-15-E2t-Isoprostane (3) and ent-PGE2 (4). To a stirred
solution of keto acid 6 (23 mg, 0.040 mmol) and pyridine
(0.03 mL) in THF/CH3CN (7 mL, 1:1, v/v) was added 52%
HF aqueous solution (0.075 mL) at 08C. The reaction
mixture was warmed to rt. After 6 h stirring at rt, another
portion of 52% HF (0.075 mL) was added and stirring was
continued for another 18 h. After addition of saturated
aqueous NaCl (5 mL) and solid NaCl (0.5 g), the mixture
was extracted with CHCl3. The combined organic extract
was dried (Na2SO4) and concentrated. The residue was chro-
matographed to furnish a mixture of ent-15-E2t-isoprostane
3 and ent-PGE2 4 (12.5 mg, 90%, 3:44.6:1) as a colorless
oil.
(5Z,8R,9R,11S,12S,13E,15R)-11,15-Bis(tert-butyldimethyl-
silyloxy)-9-hydroxyprosta-5,13-dienoic acid (8). To a
stirred solution of acetate 7 (59 mg, 0.09 mmol) in THF/
H2O/MeOH (4.5 mL, 1:1:1, v/v) was added LiOH´H2O
(38 mg, 0.90 mmol). The reaction mixture was stirred for
20 h at rt and was then acidi®ed with 0.5% HCl to pH 4 at
08C. After the addition of solid NaCl (2 g), the mixture was
extracted with CHCl3. The combined organic extract was
dried (Na2SO4) and concentrated. The residue was chromato-
graphed to yield the hydroxy acid 8 (48.5 mg, 92%) as a
colorless oil, TLC Rf0.37 (EtOAc/MeOH/AcOH95/5/
0.1); [a]D114.2 (c1.62, CHCl3); FAB MS m/z (rel
intensity) 605 (M11Na, 100), 433 (13), 319 (9), 301 (32);
IR (®lm) 3390, 2954, 2929, 2857, 1710, 1463, 1361, 1255,
1079, 1005, 971, 836, 775 cm21; 1H NMR d 5.44±5.52 (m,
2H), 5.35±5.41 (m, 1H), 5.21 (dd, 1H, J10.0 and 15.2 Hz),
4.03 (dd, 1H, J5.8 and 11.9 Hz), 3.98±4.01 (m, 1H), 3.86±
3.90 (m, 1H), 2.71 (t, 1H, J8.2 Hz), 2.33 (t, 2H,
J7.4 Hz), 2.26 (dddd, 1H, J5.3, 7.4, and 14.4 Hz), 2.19
(quint, 1H, J7.4 Hz), 2.01±2.14 (m, 3H), 1.89±1.96 (m,
1H), 1.63±1.73 (m, 3H), 1.25±1.50 (m, 9H), 0.88 (s, 9H),
0.87 (s, 12H), 0.04 (s, 6H), 0.03 (s, 3H), 0.01 (s, 3H); 13C
NMR d up 178.8, 42.8, 38.4, 33.3, 31.8, 27.3, 26.6, 24.9,
24.5, 22.6, 18.2, 18.0; down 136.5, 129.6, 129.3, 127.2,
78.0, 77.6, 73.3, 54.3, 50.8, 25.9, 25.8, 14.0, 24.3, 24.69,
24.74, 24.8; FAB HRMS calcd for C32H62O5Si2Na
605.4034, found 605.4040.
A solution of KOAc (14 mg, 0.14 mmol) in MeOH (0.5 mL)
was added to the mixture of 3 and 4 (12.5 mg, 0.036 mmol,
3:44.6:1). The reaction mixture was stirred for 4 days at rt.
After addition of saturated aqueous NaCl (5 mL), solid
NaCl (0.5 g), and AcOH (0.1 mL), the mixture was
extracted with CHCl3. The combined organic extract was
dried (Na2SO4) and concentrated. The residue was chroma-
tographed to provide ent-PGE2 4 (8.5 mg, 61% yield from 6)
as a colorless oil.
Partial data for 3. TLC Rf0.28 (EtOAc/MeOH/
AcOH95/5/0.1); FAB MS m/z (rel. intensity) 375
(M11Na, 100), 357 (79); IR (®lm) 3379, 2931, 2856,
1732, 1709, 1398, 1204, 1158, 1120, 1084, 1033,
1
973 cm21; H NMR (CD3OD) d 5.66 (dd, 1H, J6.3 and
15.3 Hz), 5.41±5.48 (m, 2H), 5.35 (dddd, 1H, J0.8, 10.0,
and 15.3 Hz), 4.28±4.29 (m, 1H), 4.01±4.08 (m, 1H), 3.04
(dd, 1H, J8.0 and 9.6 Hz), 2.68±2.73 (m, 1H), 2.58 (dd,
1H, J5.7 and 19.2 Hz), 2.46 (dt, 1H, J5.0 and 14.5 Hz),
2.31 (t, 2H, J7.4 Hz), 2.26 (dd, 1H, J1.6 and 19.2 Hz),
2.08±2.15 (m, 2H), 1.95±2.03 (m, 1H), 1.64±1.71 (m, 2H),
1.34±1.57 (m, 10H), 0.93 (t, 3H, J6.2 Hz); 13C NMR
(CD3OD) d up 219.6, 177.5, 45.6, 38.5, 34.5, 33.1, 27.9,