Syntheses of the stereoisomers of neolignans morinol C and D

Article abstract of DOI:10.1039/b211801g

Morinol C and morinol D are neolignans isolated from the Chinese medicinal herb Morina chinensis as racemates. (1R,2R)-Morinol C and (1S,2R)-morinol D were synthesized from (+)-(3R,4R)-4-(3,4-dimethoxyphenyl)-3-pivaloyloxymethyl-4-butanolide 4. On the other hand, (1S,2S)-morinol C and (1R,2S)-morinol D were synthesized from anti-aldol product 8.

Full text of DOI:10.1039/b211801g

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Syntheses of the stereoisomers of neolignans morinol C and D
Satoshi Yamauchi*a and Hidemitsu Unob
a Department of Agriculture, Ehime University, Tarumi 3-5-7, Matsuyama, Ehime,790-8566,
Japan. E-mail: syamauch@agr.ehime-u.ac.jp; Fax: ϩ81-89-977-4364
b Advanced Instrumentation Center for Chemical Analysis, Ehime University, Bunkyo-cho 2-5,
Matsuyama 790-8577, Japan
Received 4th December 2002, Accepted 12th February 2003
First published as an Advance Article on the web 12th March 2003
Morinol C and morinol D are neolignans isolated from the Chinese medicinal herb Morina chinensis as racemates.
(1R,2R)-Morinol C and (1S,2R)-morinol D were synthesized from (ϩ)-(3R,4R)-4-(3,4-dimethoxyphenyl)-3-
pivaloyloxymethyl-4-butanolide 4. On the other hand, (1S,2S)-morinol C and (1R,2S)-morinol D were synthesized
from anti-aldol product 8.
Scheme 2 shows the retrosynthetic analysis of (1R,2R) and
Introduction
(1S,2S)-morinol C and (1S,2R) and (1R,2S)-morinol D.
(1R,2R)-Morinol C would be obtained from aldehyde 5 by
using the Wittig–Horner reaction. (ϩ)-Lactone 4 could be
converted to aldehyde 5 by employing a ring opening reaction.
In the case of the synthesis of (1S,2R)-morinol D, aldehyde
6 would be transformed to (1S,2R)-morinol D by the same
method as described for (1R,2R)-morinol C. However, the
isomerization of the benzylic position should be achieved dur-
ing the conversion of (ϩ)-lactone 4 to aldehyde 6. It was
assumed that the benzylic position would be isomerized under
acidic conditions. If this isomerization is accomplished, both
(1R,2R)-morinol C and (1S,2R)-morinol D are obtained from
the same starting material (ϩ)-4. On the other hand, the trans-
formations of anti-aldol product 8, which could be prepared
by Evans’ anti-aldol6 condensation, to (1S,2S)-morinol C and
(1R,2S)-morinol D were planned. The aldehyde 7, which is an
enantiomer of aldehyde 5, would be obtained from 8. This
aldehyde could be converted to (1S,2S)-morinol C. Anti-aldol
product 8 would also be converted to (Ϫ)-lactone 4, which
could be transformed to (1R,2S)-morinol D by the same
process as described for (1S,2R)-morinol D.
Many kinds of lignans, with different degrees of oxidation and
bonding patterns of the phenylpropanoide unit, are biosyn-
thesized by many types of plant. Each lignan has many kinds
of biological activity,1 and the relationship between structure
and activity is complex.2 To understand how the structure of
lignans effects biological activity, many kinds of lignans and
their analogs must be synthesized. To achieve this aim, the
establishment of synthetic pathways is important.3
Morinol C (1) and morinol D (2) (Fig. 1), which were isolated
from the Chinese medicinal herb Morina chinensis as racemates,
are a new type of neolignans.4 The biological activity of a
racemic mixture of 1 and 2 is unknown. Since optically active
compounds were not obtained by isolation, the synthetic study
of optically active morinol C (1) and D (2) is valuable for
further research on their own activity and the effect of 1 and 2
on the biological activity of Chinese medicinal herb. This is the
first report on the synthesis of (1R,2R) and (1S,2S)-morinol
C (1) and (1S,2R) and (1R,2S)-morinol D (2). The application
of (ϩ)-lactone 4, which was previously constructed by using
threo selective aldol condensation (Scheme 1),5 to neolignan
synthesis is also shown. The absolute configuration of threo
aldol product 3 is confirmed for the first time by X-ray analysis
in this paper.
Results and discussion
Firstly, the confirmation of the absolute configuration of 3
by X-ray analysis was achieved (Fig. 2). In a previous study,5 the
Fig. 1 Morinol C and morinol D.
Fig.
2
Structure of aldol product 3 as determined by X-ray
Scheme 1 Transformation of aldol product 3 to lactone 4.
crystallography.
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 2 3 – 1 3 2 9
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Scheme 2 Retrosynthetic analysis of optically active morinol C and morinol D.
absolute configuration of the benzylic position of 3 prepared by
threo selective aldol condensation was assumed due to the
coupling constant between a benzylic proton and 2-H (J =
8.3 Hz).7 The X-ray analysis supported this result. The benzylic
position and 2-position of threo aldol product 3 were converted
to the 4 and 3 positions of (ϩ)-lactone 4, respectively (Scheme 1).
Scheme 3 shows the synthesis of (1R,2R)-morinol C (1). The
lactone ring of (ϩ)-4 was opened to hydroxy amide 9, by using
Et2NH and AlMe3,8 in 89% yield. After this, the pivaloyl ester
was hydrolyzed to the corresponding diol, which was protected
as diTIPS ether by treatment with TIPSOTf and 2,6-lutidine
in 78% yield. The fully protected amide 10 was subjected to
DIBAL-H reduction to give aldehyde 11 in 85% yield based on
47% recovery of 10. Wittig–Horner reaction of aldehyde 11
gave the trans olefin 12 in 42% yield. Production of the cis
isomer was not observed. At this stage, the construction of the
skeleton of morinol C (1) was complete. Deprotection of 12 by
n-Bu4NF gave (1R,2R)-morinol C in 77% yield.
The syntheses of (1S,2S)-morinol C and (1R,2S)-morinol D
are shown in Scheme 5. The aldol condensation of acyloxazol-
idinone 199 with 3,4-dimethoxybenzaldehyde using Me3SiCl,
Et3N, and MgCl2 in EtOAc6 gave anti-aldol product 20 in 93%
yield. After protection of the hydroxy group as TIPS ether
in 77% yield, the resulting product was subjected to LiBH4
reduction to remove the oxazolidinone group in 57% yield. The
resulting alcohol 22 was treated with TIPSCl and imidazole,
giving diTIPS ether 23 in 75% yield. Osmium oxidation fol-
lowed by NaIO4 oxidation of 23 gave (Ϫ)-aldehyde 11 in 89%
yield. This (Ϫ)-aldehyde 11 was converted to (1S,2S)-morinol
C by the same process as described for the synthesis of (1R,2R)-
morinol C. On the other hand, protection of the hydroxy group
of 22 as a pivaloyl ester (86% yield), subsequent osmium and
NaIO4 oxidation gave aldehyde 25 in 92% yield. Treatment of
this aldehyde 25 with n-Bu4NF followed by pyridinium chloro-
chromate gave (Ϫ)-lactone 4 in 72% yield. (1R,2S)-Morinol D
was obtained from (Ϫ)-lactone 4 by the same process described
1
To synthesize (1S,2R)-morinol D, isomerization at the ben-
zylic position of (ϩ)-lactone 4 was examined. Acidic conditions
were selected for this isomerization because of easy production
of the benzyl cation. This isomerization was achieved by acidi-
fication with aqueous HCl after hydrolysis of pivaloyl ester 4 in
EtOH and aqueous NaOH solution, giving hydroxy lactone
13 in 73% yield. This hydroxy lactone was converted to TIPS
ether 14 by treatment with TIPSOTf and 2,6-lutidine in 95%
yield. After lactone 14 was converted to hydroxy amide 15, by
reaction with Et2NH and AlMe3, in 85% yield, the hydroxy
group was protected as TIPS ether by using TIPSOTf and 2,6-
lutidine in 83% yield. By using the described method for the
synthesis of (1R,2R)-morinol C, the amide 16 was converted to
(1S,2R)-morinol D by reduction to aldehyde 17 (95% yield
based on 39% recovery of 16) and Wittig–Horner reaction
(46% yield), followed by desilylation (86% yield) (Scheme 4).
for the synthesis of (1S,2R)-morinol D. The H and 13C NMR
data of synthesized (1S,2S)-morinol C and (1R,2S)-morinol D
agreed with the data described in literature.4
(1R,2R)-Morinol C and (1S,2R)-morinol D were first stereo-
selectively synthesized from (ϩ)-lactone 4 in 19% overall yield
involving 6 steps and in 18% overall yield involving 7 steps,
respectively. This is a new example of utilization of (ϩ)-lactone
4. (1S,2S)-Morinol C and (1R,2S)-morinol D were also first
stereoselectively synthesized from (Ϫ)-lactone 4 prepared by
using Evans’ anti-aldol condensation. This success will con-
tribute to the biological study of morinol C and morinol D,
because the natural products are a racemic mixture.
Experimental
Melting point data (mp) are uncorrected. NMR data were
measured with a JNM-EX 400 spectrometer. IR spectra were
determined with a Shimadzu FTIR-8100 spectrophotometer.
FABMS data were measured with JEOL HX-110 spectrometers
1
The H and 13C NMR data of synthesized (1R,2R)-morinol C
and (1S,2R)-morinol D agreed with the data described in the
literature.4
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Scheme 4 Reagents and conditions (yields): (a) i) 1 M aq NaOH soln.,
EtOH, rt, 16 h; ii) 6 M aq HCl, rt, 2 h (73%); (b) TIPSOTf, 2,6-lutidine,
0 ЊC, 1 h (95%); (c) AlMe3, Et2NH, CH2Cl2, rt, 16 h (85%); (d)
TIPSOTf, 2,6-lutidine, 0 ЊC, 1 h (83%); (e) DIBAL-H, ether, 0 ЊC, 2 h
(95% based on 39% recovery of 16); (f ) (EtO)2P(O)CH2(4-MeOPh),
NaOMe, DMF, rt, 1 h (46%); (g) n-Bu4NF, THF, 0 ЊC, 2.5 h (86%).
Scheme 3 Reagents and conditions (yields): (a) AlMe3, Et2NH,
CH2Cl2, rt, 34 h (89%); (b) i) 1 M aq NaOH, EtOH, rt, 1 h; ii) TIPSOTf,
2,6-lutidine, CH2Cl2, 0 ЊC, 3 h (78%); (c) DIBAL-H, ether, 0 ЊC, 2 h
(85% based on 47% recovery of 10); (d) (EtO)2P(O)CH2(4-MeOPh),
NaOMe, DMF, rt, 1 h (42%); (e) n-Bu4NF, THF, 0 ЊC, 2.5 h (77%).
Scheme 5 Reagents and conditions (yields): (a) (i) MgCl2, Et3N, Me3SiCl, 3,4-dimethoxybenzaldehyde, EtOAc, rt, 20 h; (ii) CF3CO2H, MeOH, rt, 1
h (93%); (b) TIPSOTf, 2,6-lutidine, CH2Cl2, 0 ЊC, 1 h (77%); (c) LiBH4, MeOH, THF, rt, 16 h (57%); (d) TIPSCl, imidazole, DMF, 60 ЊC, 1.5 h (75%);
(e) (i) NMO, OsO4, acetone, tert-BuOH, H2O, rt, 16 h; (ii) NaIO4, MeOH, rt, 1 h (89%); (f ) PivCl, Pyr, rt, 1 h (86%); (g) NMO, OsO4, acetone,
tert-BuOH, H2O, rt, 16 h; (ii) NaIO4, MeOH, rt, 1 h (92%); (h) (i) n-Bu4NF, THF, 0 ЊC, 1 h; (ii) PCC, MS 4Å, CH2Cl2, rt, 16 h (72%).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 2 3 – 1 3 2 9
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and a JEOL Mstation (MS 700). Optical rotations were evalu-
ated with a Horiba SEPA-200, [α]D-values are in units of 10Ϫ1
deg cm2 gϪ1. The silica gel used was Wakogel C-300 (Wako,
200–300 mesh). Preparative TLC was conducted with Merck
silica gel 60F254 (0.5 mm thickness, 20 × 20 cm).
J 4.4 Hz, ArCHOTIPS), 6.79 (1H, d, J 7.8 Hz, ArH), 6.91 (1H,
dd, J 7.8, 1.5 Hz, ArH), 6.95 (1H, d, J 1.5 Hz, ArH); δC (CDCl3)
12.0, 12.4, 13.0, 14.2, 18.0, 18.1, 29.3, 39.8, 41.9, 46.4, 55.7,
55.8, 63.0, 72.8, 110.3, 119.4, 134.5, 147.9, 148.2, 171.5 (Found
C, 65.99; H, 10.62; N, 2.22. C35H67O5NSi2 requires C, 65.88;
H, 10.58; N, 2.20%).
Crystal structure determination of compound 3
(3R,4R)-4-(3,4-Dimethoxyphenyl)-4-(triisopropylsilyloxy)-3-
(triisopropylsilyloxy)methylbutanal 11
Crystallographic summary for 3: C33H32O7, colorless block
crystal, triclinic, P1, Z = 2 in a cell of dimensions of a = 8.962(2)
Å, b = 8.981(2) Å, c = 19.587(4) Å, α = 82.32(2)Њ, β = 91.78(2)Њ,
To a solution of amide 10 (1.49 g, 2.34 mmol) in ether (30 ml)
was added DIBAL-H (2.57 ml, 1 M in toluene, 2.57 mmol) at
0 ЊC. After the resulting solution was stirred at 0 ЊC for 2 h, 6 M
aq HCl soln. was added. The organic solution was separated,
washed with sat. aq NaHCO3 soln. and brine, and dried (Na2-
SO4). Concentration followed by silica gel column chromato-
graphy (5% EtOAc–hexane) gave aldehyde 11 (0.60 g, 1.06
mmol, 45%) as a colorless oil. Amide 8 (0.71 g, 1.11 mmol,
47%) was recovered. [α]2D0 = ϩ23 (c 1.9, CHCl3); νmax (CHCl3)/
cmϪ1 2946, 1721, 1514, 1464, 1262, 1086, 1065, 884; δH (CDCl3)
0.96–1.10 (42H, m, Si[CH(CH3)2]3), 1.94 (1H, ddd, J 16.5, 7.1,
2.0 Hz, 2-HH), 2.43 (1H, ddd, J 16.5, 6.6, 2.4 Hz, 2-HH ), 2.78
(1H, m, 3-H), 3.48 (1H, dd, J 9.8, 8.3 Hz, CHHOTIPS), 3.53
(1H, dd, J 9.8, 6.8 Hz, CHHOTIPS), 3.88 (6H, s, OCH3), 5.14
(1H, d, J 4.9 Hz, ArCHOTIPS), 6.79 (1H, d, J 8.3 Hz, ArH),
6.83 (1H, dd, J 8.3, 2.0 Hz, ArH), 6.92 (1H, d, J 2.0 Hz, ArH),
9.73 (1H, dd, J 2.4, 2.0 Hz, CHO); δC (CDCl3) 11.9, 12.3, 17.9,
18.0, 41.2, 45.1, 55.8, 64.0, 73.6, 110.2, 110.4, 119.4, 133.6,
148.2, 148.5, 202.0 (Found C, 65.46; H, 10.39. C31H58O5Si2
requires C, 65.67; H, 10.31%). (3S,4S)-11. A reaction solution
of olefin 23 (0.66 g, 1.17 mmol), NMO (0.16 g, 1.37 mmol),
and OsO4 (2% in H2O, 0.5 ml) in acetone (10 ml), tert-BuOH
(2 ml) and H2O (2 ml), was stirred at room temperature under
N2 gas for 16 h before addition of sodium thiosulfate. After
the mixture was filtered, the filtrate was concentrated. The
residue was dissolved in H2O and EtOAc. The organic solution
was separated, washed with brine, dried (Na2SO4) and concen-
trated. A reaction mixture of the residue and NaIO4 (0.30 g,
1.40 mmol) in MeOH (10 ml) was stirred at room temperature
for 1 h. After concentration, the residue was dissolved in EtOAc
and H2O. The organic solution was separated, washed with
brine, dried (Na2SO4), and evaporated. The residue was applied
to silica gel column chromatography (EtOAc–hexane 1 : 5)
to give (3S,4S)-11 (0.59 g, 1.04 mmol, 89%) as a colorless oil,
[α]2D0 = Ϫ23 (c 0.5, CHCl3).
γ = 113.31(2)Њ, V = 1434.5(6) Å3, Dcalc = 1.251 g cmϪ3, F(000)
=
572, µ = 0.873 cmϪ1, unique reflections, 7033 with I0 > Ϫ10σ
(I0). The final R1 = 0.070 (4362 reflections with I0 > 2σ (I0)).
R = 0.103 (all), Rw = 0.149 (all), goodness-of-fit = 1.21 for 732
parameters, Flack parameter = 0.0(9). Two independent
molecules exist in the unit cell and the stereochemistry is the
same. †
(3R,4R)-4-Hydroxy-4-(3,4-dimethoxyphenyl)-3-pivaloyloxy-
methyl-N,N-diethylbutanamide 9
To a solution of AlMe3 (15.5 ml, 1 M in CH2Cl2, 15.5 mmol) in
CH2Cl2 (30 ml) was added Et2NH (1.73 ml, 16.7 mmol) and
lactone 4 (2.60 g, 7.73 mmol) in CH2Cl2 (10 ml) at 0 ЊC under
N2 gas. The reaction solution was gradually warmed to room
temperature, and then stirred at room temperature for 34 h
before pouring into ice-cooled water. The resulting mixture was
extracted with EtOAc. The organic solution was washed with
sat. aq NaHSO4 soln. and brine, and dried (Na2SO4). Concen-
tration followed by silica gel column chromatography (EtOAc–
hexane = 3 : 1) gave amide 9 (2.81 g, 6.86 mmol, 89%) as a
colorless oil, [α]2D0 = ϩ15 (c 0.3, CHCl3); νmax (CHCl3)/cmϪ1 3250,
1725, 1617, 1516, 1464, 1264, 1157, 1142, 1028; δH (CDCl3)
1.08–1.15 (6H, m, (CH CH ) NC᎐O), 1.20 (9H, s, C(CH ) ),
᎐
3
2
2
3 3
2.30–2.32 (2H, m, 2-H2), 2.78 (1H, m, 3-H), 3.23 (2H, m,
CH CH NC᎐O), 3.39 (2H, m, CH CH NC᎐O), 3.86 (3H, s,
᎐
᎐
3
2
3
2
OCH3), 3.87 (3H, s, OCH3), 4.07 (1H, dd, J 11.2, 5.9 Hz,
CHHOPiv), 4.15 (1H, dd, J 11.2, 6.4, CHHOPiv), 4.50 (1H, d,
J 4.9 Hz, OH), 4.82 (1H, dd, J 4.9, 4.4 Hz, ArCHOH), 6.83
(2H, s, ArH), 6.89 (1H, s, ArH); δC (CDCl3) 13.0, 14.1, 27.2,
31.5, 38.8, 40.6, 41.7, 42.2, 55.9, 64.2, 73.5, 109.5, 111.0, 118.6,
134.7, 148.3, 149.0, 171.3, 178.4 (Found C, 64.34; H, 8.86;
N, 3.47. C22H35O6N requires C, 64.52; H, 8.61; N, 3.42%).
(3R,4R)-4-(3,4-Dimethoxyphenyl)-4-(triisopropylsilyloxy)-3-
(triisopropylsilyloxy)methyl-N,N-diethylbutanamide 10
(1R,2R)-1-(3,4-Dimethoxyphenyl)-2-(4-methoxycinnamyl)-1,3-
bis(triisopropylsilyloxy)propane 12
A reaction solution of pivaloyl ester 9 (2.81 g, 6.86 mmol) in
EtOH (25 ml) and 1 M aq NaOH soln. (25 ml) was stirred at
room temperature for 1 h before the addition of H2O and
EtOAc. The organic solution was separated, washed with brine,
and dried (Na2SO4). Concentration gave the crude diol. To a
solution of the crude diol and 2,6-lutidine (3.32 ml, 28.5 mmol)
in CH2Cl2 (20 ml) was added TIPSOTf (4.86 ml, 18.1 mmol) at
0 ЊC. The resulting reaction solution was stirred at 0 ЊC for 3 h
before addition of sat. aq NaHCO3 soln. The organic solution
was separated, washed with brine, and dried (Na2SO4). After
concentration, the residue was applied to a silica gel column
(EtOAc–hexane = 1 : 9) to give disilyl ether 10 (3.41 g, 5.34
mmol, 78%) as a colorless oil, [α]2D0 = ϩ5.6 (c 3.7, CHCl3);
νmax (CHCl3)/cmϪ1 2946, 1630, 1512, 1464, 1258, 1088, 1065,
A solution of 4-methoxybenzyl chloride (4.92 ml, 36.3 mmol)
and (EtO)3P (6.48 ml, 37.8 mmol) in DMF (24 ml) was heated
under reflux for 1 h before addition to MeONa (2.0 g,
37.0 mmol). The resulting mixture was stirred at room tem-
perature for 1 h. The resulting solution of ylide (1.26 ml,
ca. 1.91 mmol) was added to a solution of aldehyde 11 (0.46 g,
0.81 mmol) in DMF (1 ml) at 0 ЊC. After the reaction solution
was stirred at room temperature for 3 h, H2O and EtOAc were
added. The organic solution was separated, washed with brine,
and dried (Na2SO4). After evaporation of the solvent, the resi-
due was applied to a silica gel column (5% EtOAc–benzene)
to give olefin 12 (0.23 g, 0.34 mmol, 42%) as a colorless oil,
[α]2D0 = Ϫ24 (c 0.9, CHCl3); νmax (CHCl3)/cmϪ1 2944, 1510, 1466,
1248, 1090, 1067, 1030, 884; δH (CDCl3) 0.98–1.09 (42H, m,
Si[CH(CH3)2]3), 1.51 (1H, ddd, J 14.7, 8.8, 5.9 Hz, 3-HH), 2.23
(1H, m, 4-H), 2.59 (1H, m, 3-HH ), 3.33 (1H, dd, J 10.5, 9.8 Hz,
CHHOTIPS), 3.71 (1H, dd, J 10.5, 5.1 Hz, CHHOTIPS), 3.79
(3H, s, OCH3), 3.86 (3H, s, OCH3), 3.88 (3H, s, OCH3), 5.23
(1H, d, J 4.4 Hz, ArCHOTIPS), 5.99 (1H, ddd, J 15.6, 8.3, 6.3
Hz, 2-H), 6.20 (1H, d, J 15.6 Hz, 1-H), 6.79–6.83 (3H, m, ArH),
6.90 (1H, dd, J 8.3, 2.0 Hz, ArH), 6.99 (1H, d, J 2.0 Hz, ArH),
7.20 (2H, d, J 8.3 Hz, ArH); δC (CDCl3) 12.0, 12.3, 18.0, 18.1,
884; δ (CDCl ) 0.98–1.69 (48H, m, (CH CH ) NC᎐O, Si[CH-
᎐
H
3
3
2 2
(CH3)2]3), 1.66 (1H, dd, J 15.1, 9.8 Hz, 2HH), 2.54 (1H, m,
3-H), 2.71 (1H, dd, J 15.1, 3.4 Hz, 2HH ), 3.20 (2H, m,
CH CH NC᎐O), 3.35–3.49 (4H, m, CH CH NC᎐O, CH -
᎐
᎐
3
2
3
2
2
OTIPS), 3.85 (3H, s, OCH3), 3.87 (3H, s, OCH3), 5.37 (1H, d,
† CCDC reference number 199073. See http://www.rsc.org/suppdata/
ob/b2/b211801g/ for crystallographic data in .cif or other electronic
format.
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28.6, 49.5, 55.3, 55.7, 55.8, 64.3, 73.3, 110.1, 110.6, 113.9, 119.6,
126.9, 127.6, 130.3, 130.8, 134.6, 147.8, 148.2, 158.6 [Found
(HRMS) M ϩ Naϩ, 693.4352. C39H66O5Si2Na requires M ϩ
Naϩ, 693.4347]. (1S,2S)-12, [α]2D0 = ϩ24 (c 1.4, CHCl3).
lactone 14 (1.14 g, 2.79 mmol) in CH2Cl2 (5 ml) was added at
0 ЊC. The resulting reaction solution was warmed to room tem-
perature, stirred for 16 h, and poured into an ice-cooled sat.
aq NaHSO4 soln. The mixture was extracted with EtOAc. The
organic solution was separated, washed with sat. aq NaHCO3
soln. and brine, dried (Na2SO4) and concentrated. The residue
was applied to silica gel column chromatography (EtOAc–
hexane = 1 : 3) to give amide 15 (1.14 g, 2.37 mmol, 85%) as
a colorless oil, [α]2D0 = Ϫ23 (c 0.9, CHCl3); νmax (CHCl3)/cmϪ1
3455, 2869, 1611, 1516, 1464, 1260, 1235, 1140, 1063, 1028;
(1R,2R)-1-(3,4-Dimethoxyphenyl)-2-(4-methoxycinnamyl)-1,3-
propanediol 1 ((1R,2R)-morinol C)
To a solution of disilyl ether 12 (56 mg, 0.083 mmol) in THF
(5 ml) was added n-Bu4NF (0.18 ml, 1 M in THF, 0.18 mmol)
at 0 ЊC. The reaction solution was stirred at 0 ЊC for 2.5 h before
additions of sat. aq NH4Cl soln. and EtOAc. The organic
solution was separated, washed with brine, dried (Na2SO4) and
concentrated. The residue was applied to silica gel TLC (EtOAc–
hexane = 3 : 1) to give morinol C (1: 23 mg, 0.064 mmol, 77%)
as a colorless oil, [α]2D0 = Ϫ48 (c 0.3, CHCl3). 1H and 13C NMR
data agreed with that of the literature.4 (1S,2S)-morinol C,
[α]2D0 = ϩ48 (c 0.5, CHCl3).
δH (CDCl ) 0.94–1.13 (27H, m, (CH CH ) NC᎐O, Si[CH-
᎐
3
3
2 2
(CH3)2]3), 2.38–2.46 (2H, m, 2-HH, 3-H), 2.67 (1H, dd, J 17.8,
8.1 Hz, 2-HH ), 3.27 (2H, m, CH CH NC᎐O), 3.34 (2H, q, J 7.3
᎐
3
2
Hz, CH CH NC᎐O), 3.80–3.91 (2H, m, 4-H), 3.86 (3H,
᎐
3
2
s, OCH3), 3.89 (3H, s, OCH3), 4.87 (1H, br t, J 3.9 Hz,
ArCHOH), 4.95 (1H, d, J 3.9 Hz, OH), 6.81–6.89 (2H, m,
ArH), 6.95 (1H, s, ArH); δC (CDCl3) 11.8, 13.0, 14.1, 17.9, 29.1,
40.5, 42.2, 44.4, 55.8, 65.7, 75.9, 109.1, 110.9, 118.3, 136.3,
147.9, 148.8, 172.2 (Found C, 64.55; H, 9.82; N, 2.74.
C26H47O5NSi requires C, 64.82; H, 9.83; N, 2.91%). (3S,4R)-15,
[α]2D0 = ϩ23 (c 1.4, CHCl3).
(3R)-3-[(S)-(Hydroxy)(3,4-dimethoxyphenyl)methyl]-4-butano-
lide 13
A reaction solution of lactone 4 (1.00 g, 2.97 mmol) in EtOH
(17 ml) and 1 M aq NaOH soln. (17 ml) was stirred at room
temperature for 16 h before acidification with 6 M aq HCl soln.
The resulting mixture was stirred at room temperature for 2 h
before neutralization with sat. aq NaHCO3 soln. After concen-
tration, the residue was dissolved in CHCl3 and H2O. The
organic solution was separated, washed with brine, and dried
(Na2SO4). After evaporation, the residue was applied to a silica
gel column (50% EtOAc in benzene) to give hydroxy lactone 13
(0.55 g, 2.18 mmol, 73%) as colorless crystals, mp 126–127 ЊC
(MeOH), [α]2D0 = ϩ65 (c 0.4, CHCl3); νmax (CHCl3)/cmϪ1 3607,
2936, 1775, 1518, 1260, 1238, 1179, 1156, 1140, 1026; δH
(CDCl3) 2.26 (1H, d, J 2.5 Hz, OH), 2.27 (1H, dd, J 17.8, 6.8
Hz, 2-HH), 2.39 (1H, dd, J 17.8, 9.0 Hz, 2-HH ), 2.88 (1H, m,
3-H), 3.88 (3H, s, OCH3), 3.89 (3H, s, OCH3), 4.38–4.46 (2H,
m, 4-H2), 4.57 (1H, dd, J 7.8, 2.5 Hz, ArCHOH), 6.85–6.87
(3H, m, ArH); δC (CDCl3) 31.4, 42.5, 55.9, 70.5, 75.3, 108.9,
111.2, 118.5, 134.4, 145.2, 149.4, 176.7 (Found C, 61.66;
H, 6.36. C13H16O5 requires C, 61.90; H, 6.39%). (3S,4R)-13,
[α]2D0 = Ϫ65 (c 0.5, CHCl3).
(3R,4S )-4-(3,4-Dimethoxyphenyl)-4-(triisopropylsilyloxy)-3-
(triisopropylsilyloxy)methyl-N,N-diethylbutanamide 16
To a solution of alcohol 15 (0.32 g, 0.66 mmol) and 2,6-lutidine
(0.15 ml, 1.29 mmol) in CH2Cl2 (10 ml) was added TIPSOTf
(0.27 ml, 1.00 mmol) at 0 ЊC. After stirring at 0 ЊC for 1 h,
sat. aq NaHCO3 soln. was added. The organic solution was
separated, washed with brine, dried (Na2SO4), and concen-
trated. The residue was applied to a silica gel column (EtOAc–
hexane = 1 : 4) to give disilyl ether 16 (0.35 g, 0.55 mmol, 83%)
as a colorless oil, [α]2D0 = Ϫ15 (c 2.2, CHCl3); νmax (CHCl3)/cmϪ1
2944, 1624, 1514, 1464, 1258, 1084, 1065, 884; δH (CDCl3) 1.01–
1.12 (48H, m, (CH CH ) NC᎐O, Si[CH(CH ) ] ), 2.31 (1H,
᎐
3
2
2
3 2 3
m, 3-H), 2.40 (1H, dd, J = 15.1, 6.1 Hz, 2-HH), 2.62 (1H, dd,
J 15.1, 7.8 Hz, 2-HH ), 3.15 (1H, m, CH CHHNC᎐O), 3.25–
᎐
3
3.36 (3H, m, (CH CHH ) NC᎐O, CHHOTIPS), 3.41 (1H, m,
᎐
3
2
CH CHHNC᎐O), 3.85 (3H, s, OCH ), 3.87 (3H, s, OCH ), 3.97
᎐
3
3
3
(1H, dd, J = 9.8, 4.4 Hz, CHHOTIPS), 5.12 (1H, d, J 5.9 Hz,
4-H), 6.77 (1H, d, J 8.6 Hz, ArH), 6.89 (1H, d, J 8.6 Hz, ArH),
6.98 (1H, s, ArH); δC (CDCl3) 12.0, 12.5, 13.1, 14.1, 18.0, 30.2,
39.9, 41.8, 47.2, 55.6, 55.8, 62.1, 73.6, 110.2, 119.5, 136.1, 147.9,
148.4, 171.9 (Found C, 65.62; H, 10.49; N, 2.05. C35H67O5NSi2
requires C, 65.88; H, 10.60; N, 2.20%). (3S,4R)-16, [α]2D0 = ϩ15
(c 1.7, CHCl3).
(3R)-3-[(S)-(3,4-Dimethoxyphenyl)(triisopropylsilyloxy)-
methyl]-4-butanolide 14
To a solution of alcohol 13 (0.87 g, 3.45 mmol) and 2,6-lutidine
(0.83 ml, 7.13 mmol) in CH2Cl2 (10 ml) was added TIPSOTf
(1.43 ml, 5.32 mmol). The resulting reaction solution was
stirred at 0 ЊC for 1 h before addition of sat. aq NaHCO3. The
organic solution was separated, washed with brine, dried
(Na2SO4) and concentrated. The residue was purified with silica
gel column chromatography (EtOAc–hexane = 1 : 3) to give silyl
ether 14 (1.34 g, 3.28 mmol, 95%) as a colorless oil, [α]2D0 = ϩ23
(c 2.6, CHCl3); νmax (CHCl3)/cmϪ1 2946, 1775, 1518, 1466,
1266, 1163, 1142, 1115, 997; δH (CDCl3) 1.00–1.18 (21H, m,
Si[CH(CH3)2]3), 2.60 (1H, m, 3-H), 2.69 (1H, dd, J 8.8, 8.3 Hz,
2-HH), 2.74 (1H, dd, J 8.8, 8.8 Hz, 2-HH ), 3.78 (2H, d, J 4.4
Hz, 4-H), 3.88 (3H, s, OCH3), 3.89 (3H, s, OCH3), 5.40 (1H, d,
J 6.3 Hz, ArCHOTIPS), 6.84–6.87 (3H, m, ArH); δC (CDCl3)
11.9, 18.0, 31.0, 46.7, 55.9, 61.4, 82.7, 108.8, 111.1, 118.3, 131.2,
149.2, 149.3, 176.4 (Found C, 64.66; H, 8.90. C22H36O5Si
requires C, 64.67; H, 8.88%). (3S,4R)-14, [α]2D0 = Ϫ23 (c 1.2,
CHCl3).
(3R,4S )-4-(3,4-Dimethoxyphenyl)-4-(triisopropylsilyloxy)-3-
(triisopropylsilyloxy)methylbutanal 17
To a solution of amide 16 (0.46 g, 0.72 mmol) in ether (30 ml)
was added DIBAL-H (0.86 ml, 1 M in toluene, 0.86 mmol) at
0 ЊC. After the resulting solution was stirred at 0 ЊC for 2 h, 6 M
aq HCl soln. was added. The organic solution was separated,
washed with sat. aq NaHCO3 soln., and brine and dried
(Na2SO4). Concentration followed by silica gel column chrom-
atography (5% EtOAc–hexane) gave aldehyde 17 (0.24 g,
0.42 mmol, 58%). Amide 16 (0.18 g, 0.28 mmol, 39%) was
recovered. [α]2D0 = Ϫ40 (c 1.0, CHCl3); νmax (CHCl3)/cmϪ1 2946,
1721, 1514, 1464, 1262, 1094, 1064, 884; δH (CDCl3) 0.97–1.03
(42H, m, Si[CH(CH3)2]3), 2.45 (1H, m, 3-H), 2.53 (1H, ddd,
J 17.0, 7.6, 2.4 Hz, 2-HH), 2.66 (1H, ddd, J 17.0, 5.7, 1.5 Hz,
2-HH ), 3.43 (1H, dd, J 9.8, 6.8 Hz, CHHOTIPS), 3.78 (1H,
dd, J 9.8, 4.9 Hz, CHHOTIPS), 3.86 (3H, s, OCH3), 3.87 (3H,
s, OCH3), 4.89 (1H, d, J 5.9 Hz, ArCHOTIPS), 6.78 (2H, s,
ArH), 6.88 (1H, s, ArH), 9.74 (1H, dd, J 2.4, 1.5 Hz, CHO);
δC (CDCl3) 11.9, 12.6, 18.0, 18.1, 42.5, 46.2, 55.7, 55.9, 63.4,
74.5, 109.7, 110.5, 119.1, 135.9, 148.3, 148.7, 202.7 (Found C,
65.40; H, 10.38. C31H58O5Si2 requires C, 65.67; H, 10.31%).
(3S,4R)-17, [α]2D0 = ϩ40 (c 0.7, CHCl3).
(3R,4S )-4-Hydroxy-4-(3,4-dimethoxyphenyl)-3-(triisopropyl-
silyloxy)methyl-N,N-diethylbutanamide 15
To a solution of AlMe3 (5.57 ml, 1 M in hexane, 5.57 mmol) in
CH2Cl2 (14 ml) was added Et2NH (0.58 ml, 5.61 mmol) at 0 ЊC.
After the solution was stirred at 0 ЊC for 15 min, a solution of
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 2 3 – 1 3 2 9
1327

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(1S,2R)-1-(3,4-Dimethoxyphenyl)-2-(4-methoxycinnamyl)-1,3-
bis(triisopropylsilyloxy)propane 18
(4S )-4-Benzyl-3-{(2R)-2-[(S )-(3,4-dimethoxyphenyl)(triiso-
propylsilyloxy)methyl]-4-pentenoyl}-2-oxazolidinone 21
A solution of 4-methoxybenzyl chloride (4.92 ml, 36.3 mmol)
and (EtO)3P (6.48 ml, 37.8 mmol) in DMF (24 ml) was heated
under reflux for 1 h before addition to MeONa (2.0 g,
37.0 mmol). The resulting mixture was stirred at room
temperature for 1 h. The resulting ylide solution (0.41 ml,
ca. 0.97 mmol) was added to a solution of aldehyde 17 (0.23 g,
0.41 mmol) in DMF (1 ml) at 0 ЊC. After the reaction solution
was stirred at room temperature for 3 h, H2O and EtOAc were
added. The organic solution was separated, washed with brine
and dried (Na2SO4). After evaporation of the solvent, the
residue was applied to silica gel column chromatography (5%
EtOAc–benzene) to give olefin 18 (0.13 g, 0.19 mmol, 46%) as a
colorless oil, [α]2D0 = Ϫ30 (c 0.5, CHCl3); νmax (CHCl3)/cmϪ1 2959,
1510, 1464, 1248, 1102, 1064, 1030, 884; δH (CDCl3) 0.97–1.26
(42H, m, Si[CH(CH3)2]3), 1.89 (1H, m, 4-H), 2.39 (2H, dd, J 7.3,
6.6 Hz, 3-H2), 3.37 (1H, dd, J 9.8, 5.9 Hz, CHHOTIPS), 3.80–
3.86 (1H, m, CHHOTIPS), 3.80 (3H, s, OCH3), 3.86 (3H, s,
OCH3), 3.87 (3H, s, OCH3), 5.02 (1H, d, J = 4.9 Hz, 5-H), 6.05
(1H, dt, J = 16.1, 6.6 Hz, 2-H), 6.34 (1H, d, J = 16.1 Hz, 1-H),
6.77–6.84 (4H, m, ArH), 6.92 (1H, s, ArH), 7.23 (2H, d, J =
8.3 Hz, ArH); δC (CDCl3) 12.1, 12.6, 18.0, 18.1, 29.9, 51.0, 55.2,
55.7, 55.8, 62.4, 74.1, 110.0, 110.3, 113.9, 119.1, 126.9, 128.0,
130.4, 130.8, 136.8, 147.9, 148.5, 158.6 [Found (HRMS) M ϩ
Naϩ, 693.4352. C39H66O5Si2Na requires M ϩ Naϩ, 693.4347].
(1R,2S)-19, [α]2D0 = ϩ30 (c 0.8, CHCl3).
To an ice-cooled solution of anti-aldol product 20 (16.4 g,
0.039 mol) and 2,6-lutidine (9.02 ml, 0.077 mol) in CH2Cl2
(80 ml) was added TIPSOTf (12.5 ml, 0.047 mol). After stirring
at 0 ЊC for 1 h, sat. aq NaHCO3 solution was added. The
organic solution was separated, washed with sat. aq CuSO4
solution, NaHCO3 solution, and brine and dried (Na2SO4).
After concentration, the residue was applied to silica gel
column chromatography (EtOAc–hexane 1 : 6) to give silyl
ether 21 (17.0 g, 0.030 mol, 77%) as a colorless oil, [α]2D0 = Ϫ31
(c 2.5, CHCl3); νmax (CHCl3)/cmϪ1 2946, 2869, 1781, 1698, 1512,
1466, 1387, 1254, 1098, 909; δH (CDCl3) 0.92–1.00 (21H, m, iso-
Pr), 1.91 (1H, m, CHHCH᎐CH ), 2.14 (1H, m, CHHCH᎐CH ),
᎐
᎐
2
2
2.63 (1H, dd, J 13.2, 11.2 Hz, CHHPh), 3.54 (1H, dd, J 13.2, 2.9
Hz, CHHPh), 3.88 (3H, s, OCH3), 3.92 (3H, s, OCH3), 4.07
(1H, dd, J 9.0, 7.8 Hz, 5-HH), 4.12 (1H, dd, J 9.0, 2.7 Hz,
5-HH ), 4.54 (1H, m, 4-H), 4.61 (1H, m, O᎐CCH), 4.87–4.95
᎐
(2H, m, CH᎐CH ), 5.06 (1H, d, J 8.8 Hz, ArCHOTIPS), 5.62
᎐
2
(1H, m, CH᎐CH ), 6.79 (1H, d, J 8.3 Hz, ArH), 6.88 (1H, dd,
᎐
2
J 8.3, 1.5 Hz, ArH), 7.07 (1H, d, J 1.5 Hz, ArH), 7.26–7.30 (3H,
m, ArH), 7.34–7.37 (2H, m, ArH); δC (CDCl3) 12.6, 17.9, 18.1,
34.3, 38.4, 51.4, 55.8, 56.0, 66.0, 77.0, 110.2, 110.4, 116.8, 120.2,
127.2, 129.0, 129.3, 134.9, 136.0, 148.9, 149.0, 153.4, 174.6
(Found C, 68.06; H, 8.07; N, 2.27. C33H47O6NSi requires C,
68.12; H, 8.14; N, 2.41%).
(2S )-2-[(S )-(3,4-Dimethoxyphenyl)(triisopropylsilyloxy)-
methyl]-4-penten-1-ol 22
(1S,2R)-1-(3,4-Dimethoxyphenyl)-2-(4-methoxycinnamyl)-1,3-
propanediol 2 ((1S,2R)-morinol D)
To an ice-cooled solution of acyloxazolidinone 21 (17.0 g,
0.030 mol) and MeOH (1.5 ml) in THF (80 ml) was added
LiBH4 (1.6 g, 0.073 mol). The resulting reaction mixture was
stirred at room temperature for 16 h before addition of sat. aq
NH4Cl solution. The organic solution was separated, washed
with brine, and dried (Na2SO4). After concentration, the resi-
due was applied to silica gel column chromatography (EtOAc–
hexane 1 : 8) to give alcohol 22 (6.95 g, 0.017 mol, 57%) as a
colorless oil, [α]2D0 = Ϫ46 (c 1.7, CHCl3); νmax (CHCl3)/cmϪ1 3500,
2946, 2869, 1514, 1466, 1262, 1140, 1084, 1065, 1028, 884;
δH (CDCl3) 0.97–1.03 (21H, m, iso-Pr), 1.85–1.95 (2H, m,
2-H, 3-HH), 2.20 (1H, m, 3-HH ), 2.65 (1H, dd, J 5.4, 5.4 Hz,
OH), 3.58 (1H, m, 1-HH), 3.79 (1H, m, 1-HH ), 3.88 (6H, s,
OCH3), 4.88 (1H, d, J 5.4 Hz, ArCHOTIPS), 4.99–5.03 (2H, m,
To a solution of disilyl ether 18 (44 mg, 0.065 mmol) in THF
(8 ml) was added n-Bu4NF (0.14 ml, 1 M in THF, 0.14 mmol) at
0 ЊC. The reaction solution was stirred at 0 ЊC for 2.5 h before
additions of sat. aq NH4Cl soln. and EtOAc. The organic
solution was separated, washed with brine, dried (Na2SO4) and
concentrated. The residue was applied to silica gel TLC (EtOAc–
hexane = 3 : 1) to give morinol D (2: 20 mg, 0.056 mmol, 86%)
as a colorless oil, [α]2D0 = ϩ22 (c 0.5, CHCl3). 1H and 13C NMR
data agreed with that of the literature.4 (1R,2S)-morinol D, [α]2D0
= Ϫ22 (c 0.4, CHCl3).
(4S )-4-Benzyl-3-{(2R)-2-[(S )-(hydroxy)(3,4-dimethoxyphenyl)-
methyl]-4-pentenoyl}-2-oxazolidinone 20
A reaction mixture of acyloxazolidinone 19 (21.7 g, 0.084 mol),
MgCl2 (0.79 g, 0.0083 mol), Et3N (24.0 ml, 0.17 mol), 3,4-di-
methoxybenzaldehyde (16.7 g, 0.10 mol), and Me3SiCl (15.7 ml,
0.12 mol) in EtOAc (150 ml) was stirred at room temperature
for 20 h. After the mixture was filtered through silica gel with
ether, the filtrate was concentrated. The residue was dissolved in
MeOH. To this solution was added a few drops of CF3CO2H,
and then the resulting reaction mixture was stirred at room
temperature for 1 h before addition of a few drops of Et3N.
Concentration followed by silica gel column chromatography
(EtOAc–hexane 1 : 3 and 1 : 2) gave anti-aldol product 20
(33.1 g, 0.078 mol, 93%) as a colorless oil, [α]2D0 = Ϫ5.2 (c 1.7,
CHCl3); νmax (CHCl3)/cmϪ1 3494, 3025, 2919, 1779, 1698, 1518,
CH᎐CH ), 5.75 (1H, m, CH᎐CH ), 6.79–6.84 (2H, m, ArH),
᎐
᎐
2
2
6.93 (1H, s, ArH); δC (CDCl3) 12.5, 18.0, 32.4, 48.5, 55.8, 63.2,
78.2, 109.9, 110.3, 116.4, 119.2, 135.8, 136.8, 148.3, 148.7
[Found (HRMS) (Mϩ Ϫ H), 407.2619. C23H39O4Si requires
Mϩ Ϫ H, 407.2617].
(4S,5S )-5-(3,4-Dimethoxyphenyl)-5-(triisopropylsilyloxy)-4-
(triisopropylsilyloxy)methyl-1-pentene 23
A reaction solution of alcohol 22 (0.74 g, 1.81 mmol),
imidazole (0.25 g, 3.67 mmol), and TIPSCl (0.43 ml, 2.01
mmol) in DMF (3 ml) was heated at 60 ЊC for 1.5 h before
additions of NaHCO3 and EtOAc. The organic solution was
separated, washed with brine and dried (Na2SO4). Concen-
tration followed by silica gel column chromatography (2.5%
EtOAc in hexane) gave diTIPS ether 23 (0.77 g, 1.36 mmol,
75%) as a colorless oil, [α]2D0 = Ϫ14 (c 1.0, CHCl3); νmax (CHCl3)/
cmϪ1 2946, 2867, 1512, 1466, 1262, 1090, 1065, 884; δH (CDCl3)
0.98–1.10 (42H, m, iso-Pr), 1.33 (1H, m, 4-H), 2.16 (1H, m,
3-HH), 2.50 (1H, m, 3-HH ), 3.24 (1H, dd, J 10.3, 10.3 Hz,
TIPSOCHH), 3.67 (1H, dd, J 10.3, 4.9 Hz, TIPSOCHH ), 3.86
(3H, s, OCH3), 3.88 (3H, s, OCH3), 4.88–4.94 (2H, m, 1-H2),
5.23 (1H, d, J 4.4 Hz, ArCHOTIPS), 5.75 (1H, m, 2-H), 6.79
(1H, d, J 8.3 Hz, ArH), 6.89 (1H, d, J 8.3 Hz, ArH), 6.96 (1H, s,
ArH); δC (CDCl3) 12.0, 12.3, 18.0, 18.1, 29.3, 48.9, 55.7, 63.2,
73.0, 110.0, 110.6, 115.5, 119.5, 134.5, 137.9, 147.7, 148.1
1387, 1254, 1198, 1028; δH (CDCl ) 2.24 (1H, m, CHHCH᎐
᎐
3
CH ), 2.47 (1H, m, CHHCH᎐CH ), 2.59 (1H, dd, J 13.7, 9.3
᎐
2
2
Hz, CHHPh), 3.14 (1H, dd, J 13.7, 3.4 Hz, CHHPh), 3.19 (1H,
d, J 7.8 Hz, OH), 3.86 (3H, s, OCH3), 3.90 (3H, s, OCH3), 4.10
(1H, dd, J 9.3, 2.9 Hz, 5-HH), 4.13 (1H, dd, J 9.3, 9.3 Hz,
5-HH ), 4.58 (1H, m, 4-H), 4.65 (1H, ddd, J 12.7, 6.8, 3.4 Hz,
O᎐CCH), 4.83 (1H, dd, J 7.3, 7.3 Hz, ArCHOH), 4.98–5.08
᎐
(2H, m, CH᎐CH ), 5.75 (1H, m, CH᎐CH ), 6.85 (1H, d, J 8.3
᎐
᎐
2
2
Hz, ArH), 6.96–7.00 (2H, m, ArH), 7.10–7.18 (2H, m, ArH),
7.23–7.31 (3H, m, ArH); δC (CDCl3) 34.3, 37.5, 48.8, 55.3, 55.9,
65.8, 75.6, 109.3, 110.9, 117.4, 118.6, 127.3, 128.9, 129.4, 134.5,
134.7, 135.1, 148.7, 149.1, 153.5, 175.5 (Found C, 67.68; H,
6.56; N, 3.24. C24H27O6N requires C, 67.75; H, 6.40; N, 3.29%).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 2 3 – 1 3 2 9
1328

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(Found C, 68.18; H, 11.07. C32H60O4Si2 requires C, 68.03;
H, 10.70%).
d, J 5.4 Hz, 4-H), 6.73 (1H, d, J 8.3 Hz, ArH), 6.80 (1H, d,
J 8.3 Hz, ArH), 6.86 (1H, s, ArH), 9.72 (1H, br s, CHO);
δC (CDCl3) 12.3, 17.9, 18.0, 27.2, 38.8, 41.1, 41.3, 55.8, 64.4,
73.9, 110.1, 110.4, 119.2, 132.9, 148.5, 148.7, 178.0, 200.8
(Found C, 65.51; H, 9.45. C27H46O6Si requires C, 65.55; H,
9.37%).
(4S,5S )-5-(3,4-Dimethoxyphenyl)-4-pivaloyloxymethyl-5-(triiso-
propylsilyloxy)-1-pentene 24
To an ice-cooled solution of alcohol 22 (5.61 g, 0.014 mol) in
pyridine (10 ml) was added PivCl (2.09 ml, 0.017 mol). The
resulting reaction mixture was stirred at room temperature for
1 h before addition of EtOAc and H2O. The organic solution
was separated, washed with 1 M aq HCl solution and brine, and
dried (Na2SO4). After concentration, the residue was applied to
a silica gel column (EtOAc–hexane 1 : 9) to give pivaloyl ester
24 (5.82 g, 0.012 mol, 86%) as a colorless oil, [α]2D0 = Ϫ13 (c 4.1,
CHCl3); νmax (CHCl3)/cmϪ1 2946, 2869, 1721, 1514, 1466, 1262,
1159, 1092, 884; δH (CDCl3) 0.97–1.02 (21H, m, iso-Pr), 1.24
(9H, s, tert-Bu), 1.57 (1H, m, 4-H), 2.22 (1H, m, 3-HH), 2.38
(1H, m, 3-HH ), 3.81 (1H, dd, J 11.2, 8.8 Hz, PivOCHH), 3.86
(3H, s, OCH3), 3.88 (3H, s, OCH3), 4.16 (1H, dd, J 11.2, 4.4 Hz,
PivOCHH ), 4.93–4.98 (3H, m, 1-H2, 5-H), 5.73 (1H, m, 2-H),
6.75 (1H, d, J 7.8 Hz, ArH), 6.79 (1H, d, J 7.8 Hz, ArH), 6.88
(1H, s, ArH); δC (CDCl3) 12.3, 18.0, 27.3, 30.1, 38.8, 45.8, 55.7,
55.8, 63.9, 73.9, 110.1, 110.3, 116.4, 119.3, 134.3, 136.6, 148.2,
148.5, 178.2 (Found C, 68.07; H, 10.01. C28H48O5Si requires C,
68.25; H, 9.82%).
(3S,4S )-3-Pivaloyloxymethyl-4-(3,4-dimethoxyphenyl)-4-
butanolide (؊)-4
To an ice-cooled solution of silyl ether 25 (5.46 g, 0.011 mol)
in THF (50 ml) was added n-Bu4NF (12 ml, 1 M in THF,
0.012 mol). The reaction solution was stirred in an ice-bath for
1 h before addition of sat. aq NH4Cl solution. The organic
solution was separated, washed with brine and dried (Na2SO4).
After concentration, the residue was applied to a silica gel
column (EtOAc–hexane 2 : 1) to give a hemiacetal (3.30 g,
9.75 mmol). A reaction mixture of the hemiacetal (3.30 g,
9.75 mmol), PCC (2.95 g, 0.014 mol), and MS 4A (0.5 g)
in CH2Cl2 (50 ml) was stirred at room temperature for 16 h
before addition of dry ether. After the mixture was filtered, the
filtrate was concentrated. The residue was applied to silica gel
column chromatography (EtOAc–hexane 1 : 3 and 1 : 1) to give
(Ϫ)-lactone 4 (2.66 g, 7.91 mmol, 72%) as colorless crystals,
mp 80–81 ЊC, [α]2D0 = Ϫ48 (c 0.5, CHCl3). The NMR data of (Ϫ)-
lactone 4 were in good accord with those of (ϩ)-lactone 4.5
(3S,4S )-4-(3,4-Dimethoxyphenyl)-3-pivaloyloxymethyl-4-
(triisopropylsilyloxy)butanal 25
Acknowledgements
A reaction solution of olefin 22 (5.78 g, 0.012 mol), NMO
(1.64 g, 0.014 mol), and OsO4 (2% in H2O, 2 ml) in acetone
(80 ml), tert-BuOH (28 ml), and H2O (28 ml) was stirred at
room temperature under N2 gas for 16 h before addition of
sodium thiosulfate. After the mixture was filtered, the filtrate
was concentrated. The residue was dissolved in H2O and
EtOAc. The organic solution was separated, washed with brine,
dried (Na2SO4), and concentrated. A reaction mixture of the
residue and NaIO4 (3.03 g, 0.014 mol) in MeOH (10 ml) was
stirred at room temperature for 1 h. After concentration,
the residue was dissolved in EtOAc and H2O. The organic solu-
tion was separated, washed with brine, dried (Na2SO4), and
evaporated. The residue was applied to a silica gel column
(EtOAc–hexane 1 : 3) to give aldehyde 25 (5.50 g, 0.011 mol,
92%) as a colorless oil, [α]2D0 = Ϫ12 (c 4.8, CHCl3); νmax (CHCl3)/
cmϪ1 2961, 2869, 1725, 1514, 1466, 1264, 1159, 1090, 1065,
1028, 884; δH (CDCl3) 0.96–1.06 (21H, m, iso-Pr), 1.23 (9H, s,
tert-Bu), 2.06 (1H, ddd, J 16.6, 8.1, 0.9 Hz, 2-HH), 2.51 (1H,
ddd, J 16.6, 6.7, 2.9 Hz, 2-HH ), 2.91 (1H, m, 3-H), 3.87 (3H, s,
OCH3), 3.88 (3H, s, OCH3), 3.89 (1H, dd, J 11.2, 7.8 Hz, PivO-
CHH), 3.98 (1H, dd, J 11.2, 6.4 Hz, PivOCHH ), 5.00 (1H,
We measured the 400 MHz NMR data, FABMS data and
X-ray data at the Advanced Instrumentation Center for
Chemical Analysis, Ehime University. We are grateful to
Marutomo Co. for financial support.
References
1 W. D. MacRae and G. H. N. Towers, Phytochemistry, 1984, 23, 1207.
2 D. C. Ayres and J. D. Loike, Lignans, Cambridge University Press,
Cambridge, 1990.
3 R. S. Ward, Nat. Prod. Rep., 1999, 16, 75.
4 B.-N. Su, Y. Takaishi and T. Kusumi, Tetrahedron, 1999, 55, 14571.
5 S. Yamauchi and Y. Kinoshita, Biosci., Biotechnol., Biochem., 2001,
65, 1559.
6 D. A. Evans, J. S. Tedrow, J. T. Shaw and C. W. Downey, J. Am. Chem.
Soc., 2002, 124, 392.
7 H. O. House, D. S. Crumrine, A. Y. Teranishi and H. D. Olmstead,
J. Am. Chem. Soc., 1973, 95, 3310.
8 G. Stork, D. Niu, A. Fujimoto, E. R. Koft, J. M. Balkovec, J. R. Tata
and G. R. Dake, J. Am. Chem. Soc., 2001, 123, 3239.
9 D. A. Evans, T. C. Britton, R. L. Dorow and J. F. Dellaria, Jr.,
Tetrahedron, 1988, 44, 5525.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 3 2 3 – 1 3 2 9
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