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H. Azuma et al. / Bioorg. Med. Chem. 14 (2006) 1811–1818
3.2.2. trans-p-Coumaryl diacetate (30-ACA). The racemic
ACA (200 mg, 0.854 mmol) and sodium acetate (200 mg,
2.44 mmol) were dissolved in acetic acid (10 mL). After
stirring overnight at 60 ꢁC, the mixture was neutralized
with saturated aqueous NaHCO3 and extracted with
EtOAc. The organic layer was dried with Na2SO4 and
concentrated. The obtained residue was purified by col-
umn chromatography with n-hexane–EtOAc (4:1) to
give 30-ACA (120 mg, 60%) as a waxy solid; mp 45 ꢁC;
IR (KBr) 1759, 1736, 1601, 1508, 1377, 1366, 1254,
65 ꢁC in dark. After cooling, lipase was removed by fil-
tration and the filtrate was concentrated. The obtained
residue was purified by column chromatography with
n-hexane–EtOAc (10:1 to 5:1) to give crude product
(R)-4 (580 mg, slightly including by-product 5) and
unreacted (S)-3 (500 mg, 50%); 1H NMR (400 MHz,
CDCl3); d 0.19 (s, 6H), 0.98 (s, 9H), 2.09 (s, 3H), 5.22
(d, 1H, J = 10.5 Hz), 5.26 (d, 1H, J = 16.8 Hz), 6.00
(ddd, 1H, J = 5.9, 10.5, 16.8 Hz), 6.22 (d, 1H,
J = 5.9 Hz), 6.81 (d, 2H, J = 8.5 Hz), 7.21 (d, 2H,
J = 8.5 Hz). Since the 10-acetoxy group of (R)-4 could
be easily rearranged, this compound was used immedi-
ately in the next lipase-catalyzed hydrolysis.
1194, 1169, 1103, 1032, 974, 916, 854, 804 cmꢁ1 1H
;
NMR (400 MHz, CDCl3); d 2.10 (s, 3 Hz), 2.30 (s,
3H), 4.72 (dd, 2H, J = 1.2, 6.3 Hz), 6.24 (dt, 1H,
J = 15.9, 6.3 Hz), 6.63 (d, 1H, J = 15.9 Hz), 7.05 (d,
2H, J = 8.8 Hz), 7.39 (d, 2H, J = 8.8 Hz); HRMS (EI)
calcd for C13H14O4, [M]+ 234.0892; found, 234.0895
(31.2%).
3.2.6. Lipase-catalyzed hydrolysis of (R)-4. Lipase PS
(140 mg) and crude (R)-4 (580 mg) were suspended in
0.1 M phosphate buffer (50 mL, pH 7.0) and stirred
for 20 h at room temperature. The reaction mixture
was diluted with saturated brine and extracted with
EtOAc. The organic layer was dried with Na2SO4 and
concentrated. The obtained residue was purified by col-
umn chromatography with n-hexane–EtOAc (5:1) to
give (S)-3 (420 mg, 84% from rac-3).
3.2.3. 4-tert-Butyldimethylsiloxybenzaldehyde (2). To a
solution of p-hydroxybenzaldehyde 1 (2.5 g, 20 mmol)
and imidazole (1.96 g, 1.4 equiv) in dry DMF (50 mL),
a solution of TBSCl (3.7 g, 1.2 equiv) in dry DMF
(10 mL) was added dropwise at 0 ꢁC, and the mixture
was stirred for 3 h at room temperature. The resulting
mixture was concentrated in vacuo and then diluted
with EtOAc. The organic layer was washed with saturat-
ed aqueous NaHCO3, dried with Na2SO4, and concen-
trated. The obtained residue was purified by column
chromatography with n-hexane–EtOAc (20:1) to give 2
(3.87 mg, 82%) as a colorless oil; IR (NaCl) 1703,
1599, 1576, 1506, 1471, 1421, 1393, 1364, 1273, 1211,
3.2.7. (10S)-Acetoxychavicol acetate ((S)-ACA). To a solu-
tion of (S)-3 (500 mg, 1.89 mmol) in dry THF (20 mL),
tetra-n-butylammonium fluoride (1 M in THF, 2.8 mL)
was added dropwise at 0 ꢁC. After stirring for 1 h at
0 ꢁC, the reaction mixture was diluted with saturated
brine and extracted with ether, then EtOAc. The com-
bined organic layer was dried with Na2SO4 and concen-
trated. The residue was dissolved in pyridine (20 mL)
and acetic anhydride (770 mg, 4 equiv) was added to the
solution. After stirring overnight at room temperature,
the solvent was removed in vacuo, and 1 M hydrochloric
acid was added to the residue, and the mixture was
extracted with CHCl3. The organic layer was dried with
Na2SO4 and concentrated. The obtained residue was
purified by column chromatography with n-hexane–
1155, 1101, 1007, 907, 841, 800, 783, 717 cmꢁ1 1H
;
NMR (400 MHz, CDCl3); d 0.25 (s, 6H), 1.00 (s, 9H),
6.95 (d, 2H, J = 8.5 Hz), 7.79 (d, 2H, J = 6.9 Hz), 9.89
(s, 1H); HRMS (EI) calcd for C13H20O2Si, [M]+
236.1233; found, 236.1218 (34.4%).
3.2.4. Racemic 4-O-tert-butyldimethylsilyl-10-hydroxyc-
havicol (rac-3). To a solution of 2 (2 g, 8.48 mmol) in
dry THF (20 mL), vinylmagnesium bromide (1 M in
THF, 10 mL) was added dropwise at 0 ꢁC. After stirring
for 3 h at room temperature, 0.5 M hydrochloric acid
(20 mL) was added and then extracted with EtOAc.
The organic layer was dried with Na2SO4 and concen-
trated. The obtained residue was purified by column
chromatography with n-hexane–EtOAc (5:1) to give
rac-3 (1.76 g, 79%) as a pale yellow oil; IR (NaCl)
3380, 2957, 2859, 1609, 1508, 1472, 1362, 1256, 1169,
EtOAc (4:1) to give natural-type (S)-ACA (270 mg,
25
D
61%) as a colorless oil; ½aꢀ ¼ ꢁ60:1 (c 1.442, EtOH)
22
D
25
{lit.9 ½aꢀ ¼ ꢁ56:5 (c 1, EtOH)}, ½aꢀ ¼ ꢁ57:4 (c 1.67,
D
CHCl3); IR (NaCl) 1732, 1645, 1607, 1506, 1371, 1204,
1167, 1096, 1018, 912, 858, 964, 719 cmꢁ1; H NMR
1
(400 MHz, CDCl3); d 2.10 (s, 3H), 2.29 (s, 3H), 5.25 (d,
1H, J = 10.5 Hz), 5.30 (d, 1H, J = 17.1 Hz), 5.98 (ddd,
1H, J = 5.9, 10.5, 17.1 Hz), 6.26 (d, 1H, J = 5.9 Hz),
7.08 (d, 2H, J = 8.5 Hz), 7.37 (d, 2H, J = 8.5 Hz); HRMS
(FAB, direct) calcd for C13H14O4, [M]+ 234.0892; found,
234.0900 (12%); Anal. Calcd: C, 66.66; H, 6.02. Found: C,
66.54; H, 6.03.
1099, 989, 916, 839, 802, 781, 719 cmꢁ1 1H NMR
;
(400 MHz, CDCl3); d 0.19 (s, 6H), 0.98 (s, 9H), 1.89–
1.92 (br s, 1H), 5.11–5.17 (m, 1H), 5.18 (d, 1H,
J = 10.2 Hz), 5.33 (d, 1H, J = 17.1 Hz), 6.05 (ddd, 1H,
J = 5.9, 10.2, 17.1 Hz), 6.82 (d, 1H, J = 8.6 Hz), 7.23
(d, 1H, J = 8.6 Hz); HRMS (EI, direct) calcd for
C15H24O2Si, [M]+ 264.1546; found, 264.1545 (25%).
The enantiomer (R)-ACA was also prepared using
25
D
compound (R)-3; ½aꢀ ¼ þ60:0 (c 1.282, EtOH) {lit.9
22
D
25
D
½aꢀ ¼ þ57:1 (c 0.28, EtOH)}, ½aꢀ ¼ þ57:4 (c 1.67,
CHCl3); HRMS (FAB, direct) calcd for C13H14O4,
[M]+ 234.0892; found, 234.0901 (22%); Anal. Calcd: C,
66.66; H, 6.02. Found: C, 66.37; H, 6.03.
3.2.5. Lipase-catalyzed esterification of rac-3. General
procedure was carried out according to SugaiÕs meth-
od.18 To a solution of rac-3 (1 g, 3.78 mmol) and 2,6-
di-tert-butyl p-cresol (a polymerization inhibitor for vi-
nyl acetate, 25 mg, 0.11 mmol) in a mixture of freshly
distilled vinyl acetate (15 mL) and dry THF (15 mL), li-
pase PS (1.8 g) was suspended and stirred for 24 h at
3.3. Analysis
The degree of conversion in the lipase-catalyzed
esterification was estimated from the ratio between the