6452 J . Org. Chem., Vol. 61, No. 18, 1996
Notes
tially added Na2CO3 (59 mg, 0.55 mmol), NaIO4 (950 mg, 4.44
mmol) and KMnO4 (35 mg, 0.22 mmol) at rt with stirring. The
reaction mixture was stirred for 30 min, after which time TLC
showed complete reaction. Then the reaction mixture was
diluted with EtOAc (25 mL), treated with HCl (5% v/v) until
pH = 1, washed with brine (20 mL), dried over MgSO4, and con-
centrated and the residue purified by silica gel column chroma-
tography to obtain the carboxylic acid 8 as an oil (400 mg, 83%
yield), the sulfoxide 9 (50 mg, 10% yield), and traces of the
for 2 h. Then, ether (25 mL) was added, and the stirring was
continued for 10 min. The mixture was dried with MgSO4 and
filtered through a pad of Celite and the residue washed with
ether (3 × 10 mL). The combined organic phases were concen-
trated, and the crude obtained was purified by silica gel flash
chromatography, yielding 2 (236 mg, 90% yield), as a white
solid: mp 108-9 °C; [R]25D ) +26.2 (c 1.6, CHCl3) [lit.7 mp 110-
11 °C, [R]25 ) +24 (c 1.37, CHCl3)]; 1H NMR (CDCl3) δ 0.88 (t,
D
J ) 6.6 Hz, 3 H), 1.20-1.32 (br s, 20 H), 1.36 (d, J ) 7.0 Hz, 3
H), 1.41 (m, 1 H), 1.51 (m, 1 H), 1.70 (m, 1 H), 1.80 (m, 1 H),
2.67 (dd, J ) 11.1, 9.2 Hz, 1 H), 2.97 (dq, J ) 11.1, 7.0 Hz, 1 H),
4.47 (dt, J ) 9.2, 3.9 Hz, 1 H); 13C-NMR (CDCl3) δ 14.1 (q), 14.5
(q), 22.6 (t), 25.3 (t), 29.2 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.6 (t),
29.6 (t), 31.9 (t), 34.9 (t), 39.8 (d), 54.0 (d), 79.5 (d), 175.8 (s),
176.7 (s); IR (CHCl3) (cm-1) 3445, 2928, 2855, 1771, 1727, 1647,
1458, 1188, 973; MS m/ z (relative intensity) 328 (M + 2)+ (3),
327 (M + 1)+ (14), 326 (M)+ (24), 281 (100), 253 (55), 97 (40), 69
(68).
sulfone (<3% yield). Compound 8: [R]25 ) +51.4 (c 1.43,
D
CHCl3); 1H NMR (CDCl3) δ 0.88 (t, J ) 6.8 Hz, 3 H), 1.20-1.31
(br s, 20 H), 1.39 (m, 1 H), 1.56 (m, 2 H), 1.62 (s, 3 H), 1.76 (m,
1 H), 3.05 (d, J ) 10.1 Hz, 1 H), 4.66 (m, 1 H), 5.36 (br s, 1 H),
7.34 (m, 2 H), 7.42 (m, 1 H), 7.56 (m, 2 H); 13C-NMR (CDCl3) δ
14.1 (q), 22.7 (q), 22.8 (t), 25.5 (t), 29.1 (t), 29.2 (t), 29.3 (t),
29.4 (t), 29.5 (t), 29.5 (t), 29.6 (t), 29.7 (t), 29.7 (t), 29.8 (t), 31.9
(t), 34.3 (t), 53.5 (s), 58.3 (d), 77.7 (d), 128.3 (s), 128.9 (d), 130.3
(d), 137.6 (d), 171.5 (s), 173.9 (s); IR (CHCl3) (cm-1) 3689, 3022,
2928, 2855, 1765, 1731, 1603, 1467, 1377, 1221, 976; MS m/ z
(relative intensity) 435 (M + 1)+ (15), 434 (M)+ (48), 324 (10),
279 (35), 211 (78), 110 (50), 57 (100). Anal. Calcd. for
P r ep a r a tion of Rocella r ic Acid Meth yl Ester (11). To a
solution of rocellaric acid (2) (80 mg, 0.24 mmol) in ether (2.5
mL, 0.1 M) was added an ethereal diazomethane solution until
a yellow color persisted. Then some drops of acetic acid were
added to obtain a colorless solution that was concentrated. The
residue was purified by column chromatography, yielding 11 (81
mg, 97% yield) as a white solid: mp 37-38 °C, [R]25D ) +22.1 (c
C
25H38O4S: C, 69.09; H, 8.81; S, 7.38. Found: C, 68.91; H, 8.62;
S, 7.15.
P r ep a r a tion of (+)-P r otolich ester in ic Acid (1). To a
stirred solution of the lactone 8 (400 mg, 0.92 mmol) in a biphasic
solvent system (8 mL of CH3OH-0.25 mL of C6H6-1.9 mL of
H2O, 0.1 M) was added NaIO4 (400 mg, 1.84 mmol) at rt. The
reaction mixture was vigorously stirred for 50 h and extracted
using CH2Cl2 (3 × 15 mL). The resulting organic solution was
concentrated, and the crude product was purified by silica gel
flash chromatography, to yield 9, as an isomeric mixture (228
mg, 55% yield) and remaining starting material 8 (160 mg, 40%).
A solution of the mixture of sulfoxides 9 (228 mg, 0.51 mmol)
in dry toluene (5 mL, 0.1 M) was submitted to reflux (110 °C)
for 1 h. The solvent was evaporated, and the residue was
purified by silica gel column chromatography to yield (+)-
protolichesterinic acid (1) (140 mg, 85% yield), as a solid: mp
103-4 °C; [R]25D ) +14.2 (c 0.95, CHCl3) [lit.6 for the enantiomer,
0.65, CHCl3) [lit.7 for the enantiomer, mp 39 °C, [R]25 ) -22.5
D
(c 2.18, CHCl3)]; 1H NMR (CDCl3) δ 0.88 (t, J ) 6.8 Hz, 3 H),
1.26-1.30 (br s, 20 H), 1.33 (d, J ) 7.1 Hz, 3 H), 1.49 (m, 2 H),
1.74 (m, 2 H), 2.65 (dd, J ) 11.4, 9.3 Hz, 1 H), 2.94 (dq, J )
11.4, 7.1 Hz, 1 H), 3.77 (s, 3 H), 4.44 (dt, J ) 9.3, 4.2 Hz, 1 H);
13C-NMR (CDCl3) δ 14.1 (q), 14.4 (q), 22.6 (t), 25.2 (t), 29.2 (t),
29.3 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.5 (t), 29.6 (t), 29.7 (t), 31.8
(t), 34.8 (t), 39.8 (d), 52.5 (q), 54.1 (d), 79.5 (d), 171.1 (s), 176.7
(s); IR (CHCl3) (cm-1) 2928, 2855, 1773, 1736, 1603, 1439, 1261,
1176, 1001; MS m/ z (relative intensity) 342 (M + 2)+ (6), 341
(M + 1)+ (30), 340 (M)+ (8), 267 (16), 129 (30), 69 (100).
P r ep a r a tion of Dih yd r op r otolich ester in ic Meth yl Ester
(12). To a solution of 11 (45 mg, 0.13 mmol) in dry methanol
(1.3 mL, 0.1 M) was added sodium hydride (8 mg, 0.26 mmol,
80% in mineral oil). This mixture was heated to 60 °C for 4 h.
The mixture was diluted with ethyl ether (10 mL), washed with
an aqueous HCl solution (15% w/v, 10 mL) and brine (10 mL),
dried over MgSO4, and concentrated, and the residue was
purified by silica gel column chromatography to obtain the
methyl esters 11 (20 mg, 44% yield) and 12 (19 mg, 42% yield)
mp 103-5 °C, [R]25 ) -15 (c 1, CHCl3)]; 1H NMR (CDCl3) δ
D
0.88 (t, J ) 6.7 Hz, 3 H), 1.20-1.35 (m, 20 H), 1.36-1.53 (m, 2
H), 1.73 (m, 2 H), 3.62 (m, 1 H), 4.80 (m, 1 H), 6.01 (d, J ) 2.4
Hz, 1 H), 6.46 (d, J ) 2.9 Hz, 1 H); 13C-NMR (CDCl3) δ 14.1 (q),
22.6 (t), 24.7 (t), 29.1 (t), 29.3 (t), 29.4 (t), 29.5 (t), 29.5 (t), 29.5
(t), 29.6 (t), 31.8 (t), 31.9 (t), 35.7 (t), 49.5 (d), 78.9 (d), 125.8 (t),
132.5 (s), 168.2 (s), 173.9 (s); IR (CHCl3) (cm-1) 3020, 2928, 2855,
1761, 1733, 1466, 1398, 1266, 1146, 958; MS m/ z (relative
intensity) 326 (M + 2)+ (3), 325 (M + 1)+ (14), 324 (M)+ (19),
279 (100), 155 (27), 57 (48). Anal. Calcd. for C19H32O4: C, 70.32;
H, 9.95. Found: C, 69.85; H, 9.86.
as a white solid: mp 49-50 °C; [R]25 ) +47.2 (c 0.18, CHCl3)
D
[lit.7 for the enantiomer, mp 58-60 °C, [R]25 ) -47 (c 0.64,
D
CHCl3)]; 1H NMR (CDCl3) δ 0.88 (t, J ) 6.7 Hz, 3 H), 1.20 (d, J
) 7.5 Hz, 3 H), 1.24-1.34 (br s, 20 H), 1.49 (m, 2 H), 1.66 (m, 2
H), 2.97 (dq, J ) 9.3, 7.5 Hz, 1 H), 3.10 (dd, J ) 9.3, 6.5 Hz, 1
H), 3.75 (s, 3 H), 4.70 (dt, J ) 6.5, 6.5 Hz, 1 H); 13C-NMR (CDCl3)
δ 11.8 (q), 14.0 (q), 22.6 (t), 25.3 (t), 29.2 (t), 29.3 (t), 29.3 (t),
29.4 (t), 29.5 (t), 29.5 (t), 29.6 (t), 31.9 (t), 34.7 (t), 37.1 (d), 50.0
(d), 52.1 (q), 79.4 (d), 170.5 (s), 177.2 (s); IR (CHCl3) (cm-1) 2928,
2855, 1772, 1738, 1461, 1439, 1223, 1216, 1203, 989; MS m/ z
(relative intensity) 342 (M + 2)+ (1), 341 (M + 1)+ (3), 340 (M)+
(7), 281 (100), 157 (34), 129 (59), 101 (62), 69 (89).
P r ep a r a tion of (3S,4S,5R)-4-[(1S)-1,2-Dih yd r oxyeth yl]-
3-m eth yl-5-tr id ecyld ih yd r ofu r a n -2-on e (10). To a stirred
solution of the diol 6 (500 mg, 1.11 mmol) in 95% EtOH (3.7
mL) were added anhydrous NiCl2 (2.88 g, 22.2 mmol) and NaBH4
(420 mg, 11.1 mmol) at 0 °C. The reaction mixture was
vigorously stirred under H2 (1 atm) for 30 min at rt. The
reaction mixture was diluted in EtOAc (25 mL) and filtered
through a pad of Celite. The combined organic phases were
concentrated, and the crude was purified by silica gel chroma-
tography, yielding 10 (311 mg, 82% yield) as a white solid: mp
P r ep a r a t ion of Dih yd r op r ot olich est er in ic Acid (3).
Meth od A. To a stirred solution of lactone 12 (10 mg, 0.029
mmol) in THF:H2O (5:1, 0.3 mL) was added NaOH (6 mg, 0.15
mmol). The reaction was stirred for 1 h, after which time TLC
showed that the starting material had disappeared. Then,
concentrated HCl was added at 0 °C until pH ≈ 1 was reached,
and the mixture was extracted with AcOEt (4 × 5 mL). The
combined organic phases were washed with 10 mL of a saturated
solution of brine, dried, and evaporated in vacuo, and the residue
was purified by column chromatography to give 3 (9 mg, 95%
yield) as a white solid.
62-65 °C; [R]25 ) +17.1 (c 0.82, CHCl3); 1H NMR (CDCl3) δ
D
0.87 (t, J ) 6.8 Hz, 3 H), 1.20-1.35 (br s, 19 H), 1.27 (d, J ) 7.3
Hz, 3 H), 1.39 (m, 1 H), 1.56 (m, 2 H), 1.78 (m, 1 H), 1.87 (dt, J
) 7.8, 7.3 Hz, 1 H), 2.57 (dq, J ) 7.3, 7.3 Hz, 1 H), 2.85 (br s, 2
H), 3.53 (dd, J ) 10.8, 7.5 Hz, 1 H), 3.70 (dd, J ) 10.8, 3.0 Hz,
1 H), 3.75 (ddd, J ) 7.5, 7.3, 3.0 Hz, 1 H), 4.43 (ddd, J ) 8.4,
7.8, 2.7 Hz, 1 H); 13C-NMR (CDCl3) δ 14.1 (q), 15.7 (q), 22.7 (t),
25.8 (t), 29.3 (t), 29.3 (t), 29.4 (t), 29.4 (t), 29.5 (t), 29.6 (t), 29.6
(t), 29.7 (t), 31.9 (t), 36.2 (t), 37.9 (d), 50.8 (d), 65.0 (t), 72.4 (d),
80.8 (d), 179.4 (s); IR (CHCl3) (cm-1) 3444, 2928, 2855, 1760,
1647, 1458, 1276, 1193; MS m/ z (relative intensity) 343 (M +
1)+ (7), 324 (M - H2O)+ (9), 311 (15), 281 (44), 141 (90), 71 (100).
Anal. Calcd for C20H38O4: C, 70.12; H, 11.19. Found: C, 70.48;
H, 10.80.
Meth od B. A mixture of (+)-Protolichesterinic acid (1) (20
mg, 0.062 mmol) and Pd/C 10% (4 mg, 20% wt) in dry methanol
(1 mL) was stirred at rt under atmosphere of H2 (≈ 1 atm). The
reaction was stirred for 6 h, after which time TLC showed the
end of the reaction. The solution was filtered, and the filter was
washed with ethyl acetate (3 × 5 mL). The combined organic
phases were concentrated, and the crude obtained was purified
by flash chromatography, yielding 2 (2.6 mg, 13% yield) and 3
P r ep a r a tion of (+)-Rocella r ic Acid (2). To a stirred
solution of the lactone 10 (275 mg, 0.8 mmol) in a biphasic
solvent system (2 mL of CH3CN-2 mL of CCl4-3 mL of H2O)
was added NaIO4 (430 mg, 2 mmol) and RuCl3‚xH2O (17 mg,
0.08 mmol) at rt. The reaction mixture was vigorously stirred
(15.4 mg, 76% yield) as a white solid: mp 101-102 °C; [R]25
)
D
+41.5 (c 0.55, CHCl3) [lit.16c mp 106 °C, [R]25 ) +34.6 (c 2.54,
D