KATO ET AL.
3
The crude product was purified by medium-pressure chro-
matography (Isolera, eluent: 5:95 n-hexane/EtOAc hexane
to 40:60 n-hexane/EtOAc) to afford 10 (7.26 g, 81%, syn:anti
and lithium hydroxide monohydrate (290 mg, 6.91 mmol)
in a mixture of THF (60 mL) and water (20 mL). The
mixture was stirred at room temperature for 2.5 hours.
The reaction mixture was acidified to pH 2 with 1M HCl.
The solution was extracted three times with AcOEt, and
the combined organic layers were washed with brine.
The organic layer was dried over anhydrous Na SO . The
=
90:10) as yellow oil.
2.2.2 | Synthesis of 13 and 14
2
4
crude product was purified by silica-gel column chroma-
PivCl (2.1 mL, 13.7 mmol) was added to a solution of
tography (E O/n-hexane/AcOH = 70/30/0.5) to afford
t2
25
(
±)-coronafacic acid ((±)-3) (1.90 g, 9.10 mmol) and Et N
(+)-3 (631 mg, 89%) as a white solid. [α]
= +121
D
3
(
7.9 mL, 48.5 mmol) in CH Cl (100 mL), and the mixture
(c 0.98, MeOH). All spectral data of (+)-3 were identical
to those reported.
2
2
8
was stirred for 2 hours. The resulting solution was added
to a mixture of LiCl (1.70 g, 27.5 mmol), (S)-4-isopropyl-2-
oxazolidinone (2.42 g, 18.2 mmol), and DMAP (110 mg,
9
10 μmol) at room temperature, and the mixture was
2.2.4 | Synthesis of (−)-coronafacic acid
((−)-3)
stirred for 16 hours. The reaction was quenched with 1M
HCl, and the mixture was extracted with CH Cl . The com-
2
2
bined organic layers were washed with brine, dried over
Na SO , and concentrated under reduced pressure. The
crude product was purified by silica-gel column chroma-
30% H O aq. (1.5 mL, 14.7 mmol) was added dropwise
2
2
ꢀ
at 0 C to a solution of compound 14 (1.10 g, 5.29 mmol)
and lithium hydroxide monohydrate (290 mg,
6.91 mmol) in a mixture of THF (60 mL) and water
(20 mL). The mixture was stirred at room temperature
for 3.5 hours. The reaction mixture was acidified to pH
2 with 1M HCl. The solution was extracted three times
with AcOEt, and the combined organic layers were
washed with brine. The organic layer was dried over
anhydrous Na SO . The crude product was purified by
2
4
tography (AcOEt/n-hexane = 80/20) to afford 13 and 14.
2
2
Compound 13: yellow oil, 1.20 g, 41% yield. [α]
=
D
1
+
87.0 (c = 1.81, CHCl ). H NMR (400 MHz, CDCl ); δ
3
3
H
6
8
7
1
1
.27 (s, 1H), 4.59 (ddd, J = 8.9, 6.1, 4.6 Hz, 1H), 4.33 (t, J =
.9Hz, 1H), 4.17 (dd, J = 8.9, 6.1 Hz, 1H), 3.31 (dt, J = 9.7,
.4 Hz, 1H), 2.48-2.13 (m, 6H), 1.88 (dt, J = 13.0, 4.7 Hz,
H), 1.76 (ddd, J = 10.0, 7.9, 7.0 Hz, 1H), 1.54-1.46 (m, 2H),
.27 (dt, J = 13.0, 10.0 Hz, 1H), 0.97 (t, J = 7.4 Hz, 3H), 0.94
2
4
silica-gel column chromatography (E O/n-hexane/
t2
13
(d, J = 6.9 Hz, 3H), 0.93 (d, J = 6.9 Hz, 3H); C NMR
AcOH = 70/30/0.5) to afford (−)-3 (579 mg, 81%) as a
25
(
100 MHz, CDCl ); δ 219.99, 170.38, 153.73, 141.32,
white solid. [α]
= −118 (c 1.01, MeOH). All spectral
3
C
D
1
2
1
33.75, 63.27, 57.84, 46.07, 37.87, 37.19, 36.02, 28.31, 27.57,
data of (−)-3 were identical to those previously
reported.
−1
9
6.66, 25.65, 17.80, 15.16, 11.22; IR (film) cm : 2962, 1782,
+
739, 1682, 1288, 756; HRMS (ESI, positive) m/z [M + Na]
calcd for C H NO Na: 342.1676, found: 342.1669.
18
25
4
2
2
Compound 14: yellow oil, 1.18 g, 40% yield. [α]
=
2.3 | Chiral HPLC analysis
D
1
+
21.4 (c = 1.79, CHCl ). H NMR (400 MHz, CDCl ); δ
3
3
H
6
.08 (s, 1H), 4.44 (dt, J = 8.7, 4.0 Hz, 1H), 4.31 (t, J = 8.7
2.3.1 | Coronafacic acid methyl ester
17 and ent-17
Hz, 1H), 4.17 (dd, J = 8.7, 4.0 Hz, 1H), 3.08 (dt, J = 10.0, 7.5
Hz, 1H), 2.58-2.16 (m, 6H), 1.91-1.82 (m, 2H), 1.56-1.35 (m,
2
H), 1.21 (dt, J = 13.0, 10.5 Hz, 1H), 0.95 (t, J = 7.4 Hz,
Optical purities were determined by chiral HPLC ana-
lyses on a Chiralpak IA ϕ4.6 × 250 mm column (Daicel
Co, Ltd, Japan) eluting with 99% n-hexane containing
1% EtOH at 0.5 mL/min. Under these conditions, good
separation of each enantiomer was achieved:
coronafacic acid methyl ester 17 at Rt = 28.3 min and
ent-17 at Rt 25.9 min. Enantiomeric excess was calcu-
lated from the ratio of peak areas (mAu s) at 230 nm.
Chiral HPLC analysis of 6 ng of the synthetic 17 gave a
ratio of 17: ent-17 = 2328: 8.74, which corresponded to
99.6% ee. According to the above-mentioned procedure,
Chiral HPLC analysis of 10 ng of the synthetic ent-17
gave a ratio of 17: ent-17 = 8.94: 5021, which cor-
responded to 99.8% ee.
13
3H), 0.95 (d, J = 7.0 Hz, 3H), 0.91 (d, J = 7.0 Hz, 3H);
C
NMR (100 MHz, CDCl ); δ 219.89, 170.44, 153.53, 138.79,
3
C
1
2
1
33.11, 63.26, 59.03, 46.26, 38.00, 36.97, 36.93, 28.29, 27.71,
7.53, 25.66, 17.95, 14.75, 11.15; IR (film) cm : 2962, 1786,
739, 1689, 1300, 748; HRMS (ESI, positive) m/z [M + Na]
−1
+
calcd for C H NO Na: 342.1676, found: 342.1679.
18
25
4
2
.2.3 | Synthesis of (+)-coronafacic acid
((+)-3)
3
0
0% H O aq. (1.5 mL, 14.7 mmol) was added dropwise at
2
2
ꢀ
C to a solution of compound 13 (1.10 g, 5.29 mmol)