Asymmetric synthesis of machilin C and its analogue

Article abstract of DOI:10.2478/s11696-010-0040-8

Full details of the asymmetric total synthesis of erythro-8-O-4′-neolignan, machilin C, and its analogue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was achieved from simple vanillin in eight to twelve steps.

Full text of DOI:10.2478/s11696-010-0040-8

Chemical Papers 64 (5) 630–636 (2010)
DOI: 10.2478/s11696-010-0040-8
ORIGINAL PAPER
Asymmetric synthesis of machilin C and its analogue
Yamu Xia*, Wei Wang
College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
Received 27 October 2009; Revised 22 January 2010; Accepted 1 February 2010
Full details of the asymmetric total synthesis of erythro-8-O-4ꢀ-neolignan, machilin C, and its ana-
logue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction
that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred
with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was
achieved from simple vanillin in eight to twelve steps.
c
ꢀ 2010 Institute of Chemistry, Slovak Academy of Sciences
Keywords: neolignans, machilin C, perseal A, asymmetric synthesis
Introduction
efficiency, poor enantioselective processes and from
chiral synthesis give threo-8-O-4ꢀ neolignans (Sefkow,
2003; Zacchino, 1994; Curti et al., 2006; Peng et al.,
2005).
Machilin C is an annual 8-O-4ꢀ neolignan first iso-
lated from the bark of Machilus thunbergii used as
traditional Chinese medicine for the treatment of con-
tusion and sprain (Shimomura et al., 1987). 8-O-4ꢀ
Neolignan comprises a large group of secondary plant
metabolites which are biochemically related to the
shikimic acid pathway (Ward, 1999). These products
are formed in nature by oxidative coupling of two
phenyloropanoid units whose site of connection deter-
mines their classification into 8-O-4ꢀ neolignan (C—
O—Cꢀ-linkages). Many 8-O-4’ neolignans display var-
ious interesting biological activities, including antiox-
idant, inhibitory on seed germination, antimalarial
(Mei et al., 2009; Cutillo et al., 2003; Zhang et al.,
2001; Ridley, 2002).
Nature itself offers an extensive library of rep-
resentatives of 8-O-4ꢀ neolignan. However, obtaining
supplies from nature is an arduous task due to the
low quantity of isolable compounds and the fact that
most of the isolated neolignans present themselves
as racemic mixtures (Barata et al., 2000). Besides,
the alternative of obtaining useful quantities of enan-
tiopure materials via synthesis has not been carefully
pursued. Most of the synthetic studies have given
rise to mixtures of syn and anti configured prod-
ucts, while many existing routes suffering from low
Herein, an efficient asymmetric synthesis of ery-
thro-8-O-4ꢀ neolignans is presented. Its stereochem-
ical outcome is dependent upon the Sharpless di-
hydroxylation reaction and the Mitsunobu reaction
steps. By this method, machilin C [alternative names:
erythro-machilin, (1S,2R)-machilin, and 4-((1S, 2R)-
1-hydroxy-2-(2-methoxy-4-((E)-prop-1-enyl)phenoxy)
propyl)-2-methoxyphenol (according to IUPAC)] and
its analogue, perseal A [alternative names: erythro-
perseal, (1S,2R)-perseal, and 4-((1S,2R)-1-(4-(benzyl-
oxy)-3-methoxyphenyl)-1-hydroxypropan-2-yloxy)-3-
methoxybenzaldehyde (according to IUPAC)], iso-
lated from the leaves of Persea obovatifolia (Tsai et
al., 1996), were obtained for the first time.
Experimental
Melting points were taken on a Gallenkamp melt-
ing point apparatus and are uncorrected. Optical
rotations were determined on a Perkin–Elmer 341
polarimeter. Infrared spectra (in KBr pellets) were
1
recorded on a Nicolet NEXUS 670 FTIR. H and 13C
NMR spectra were recorded on a Mercury Plus 300
MHz and Bruker 500 MHz spectrometers. Electron
*Corresponding author, e-mail: xiaym@qust.edu.cn

Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
631
impact mass spectra were recorded on a ZAB-HS spec-
trometer. HRMS were obtained on a Bruker Daltonics
APEXII47e spectrometer. Flash column chromatog-
raphy was performed on silica gel (200–300 mesh)
(Qingdao Haiyang Chemical Co. Ltd, China) and TLC
measurements were performed on silica gel GF254
plates (Qingdao Haiyang Chemical Co. Ltd, China).
Vanillin, benzyl chloride (BnCl), butyllithium (BuLi),
methyl chloromethyl ether (MOMCl), ethyl (triph-
ether/EtOAc (ϕr = 6 : 1) as eluent. Compound V
(9.5 g) was obtained as white crystals.
(1S,2S)-1-(4-(Benzyloxy)-3-methoxyphenyl)
propane-1,2,3-triol (VI)
AD-mix-α (42 g) and MeSO2NH2 (2.9 g) were
added to a stirred solution of tert-BuOH (50 mL) and
H2O (50 mL), and the mixture was stirred at room
temperature until both phases were clear. After cool-
ing to 0◦C, compound V (8.1 g, 30 mmol) was added
at once and the mixture was stirred vigorously at 0◦C
until TLC revealed the absence of V. Then, the reac-
tion was quenched by an addition of Na2SO3 (45 g)
at 0◦C, the reaction mixture was heated to room tem-
perature and stirred for 0.5 h followed by extraction
with EtOAc (3 × 100 mL). The extracts were dried
over MgSO4, filtered and the solvent was distilled off
under reduced pressure. The residue was purified by
flash chromatography using petroleum ether/EtOAc
(ϕr = 1 : 1) as eluent. Compound VI (8.6 g) was ob-
tained as white crystals in 93 % e.e. [α]2D0 = −71.0◦
(c = 1.0, acetone). HRMS calculated for C17H24NO5
(M + NH+4 ): 322.1649. Found: 322.1652.
—
enylphosporanylidene)acetate (Ph P CHCOOEt),
—
3
ethyltriphenylphosphonium bromide, AlCl3, LiAlH4
(LAH), NaH, AD-mix-α, MeSO2NH2, 4-toluenesulfo-
nyl chloride (TsCl), 3,4-dihydro-2H-pyran (DHP),
triphenylphosphine (Ph3P), pyridinium 4-toluenesul-
fonate (PPTS), diethyl azodicarboxylate (DEAD),
10 % palladium on charcoal (10 % Pd/C), and
the solvents used are commercially available prod-
ucts (Sinopharm Chemical Reagent Co. Ltd, Tianjin,
China; Alfa Aesar, USA).
4-Benzyloxy-3-methoxybenzaldehyde (III)
Vanillin (10.4 g, 70 mmol) and benzyl chloride (7.3
g, 70 mmol) were added to a well-stirred solution of
K2CO3 (9.7 g) in ethanol (100 mL). The mixture was
heated under reflux for 4 h and then concentrated un-
der diminished pressure. The residue was dissolved in
EtOAc (100 mL), filtered, and washed in 3 × 20 mL
of 10 % aqueous NaOH and saturated aqueous NaCl
solution, respectively. The organic extract was dried
over MgSO4, filtered, and the solvent was evaporated
under reduced pressure to give the crude product. Col-
orless crystals of III (15.3 g) were obtained by recrys-
tallization from ethanol.
(2S,3S)-3-(4-(Benzyloxy)-3-methoxyphenyl)-
2,3-dihydroxypropyl benzenesulfonate (VII)
A solution of TsCl (3.8 g, 20 mmol) in CH2Cl2
(30 mL) was added at 0◦C to compound VI (6.1 g,
20 mmol) and pyridine (20 mL) in CH2Cl2 (40 mL).
The mixture was stirred at room temperature for 24 h
and then extracted with a 1 M HCl solution (3 × 40
mL). The organic layer was washed with 50 mL of
NaHCO3 and NaCl saturated solutions, respectively,
dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by flash chromatog-
raphy using petroleum ether/EtOAc (ϕr = 3 : 1) as
eluent. Compound VII (7.6 g) was obtained as amor-
phous powder in 95 % e.e. [α]2D0 = −42.3◦ (c = 0.5,
CHCl3). HRMS calculated for C24H30NO7S (M +
NH+4 ): 476.1738. Found: 476.1732.
(E)-Ethyl 3-(4-benzyloxy)-3-methoxyphenyl)
acrylate (IV)
—
—
Compound III (14.6 g, 60 mmol) and Ph P
3
CHCOOEt (20.9 g, 60 mmol) in dry benzene (50 mL)
were heated under reflux for 10 h. The solvent was
evaporated under reduced pressure and the residue
was purified by flash chromatography using petroleum
ether/EtOAc (ϕr = 9 : 1) as eluent. Compound IV
(13.6 g) was obtained as white crystals.
(1S,2S)-1-(4-(Benzyloxy)-3-methoxyphenyl)-
2,3-epoxypropan-1-ol (VIII)
(E)-3-(4-Benzyloxy)-3-methoxyphenyl)prop-2-
en-1-ol (V)
Compound VI (6.9 g, 15 mmol) was added to a so-
lution of K2CO3 (2.1 g, 15 mmol) in MeOH (20 mL)
and the mixture was stirred at room temperature for 5
h. The solvent was evaporated under diminished pres-
sure, the residue was dissolved in EtOAc and washed
with 3 × 10 mL of water and saturated aqueous solu-
tion of NaCl, respectively. Organic extract was dried
over MgSO4, concentrated under reduced pressure,
and the residue was purified by flash chromatography
using petroleum/EtOAc (ϕr = 8 : 1) as eluent. Com-
pound VIII (4.1 g) was obtained as colorless liquid in
92 % e.e. [α]2D0 = −36.2◦ (c = 0.6, CHCl3). HRMS cal-
Dry AlCl3 (5.3 g, 40 mmol) was added at 0◦C to
a suspension of LiAlH4 (4.5 g, 120 mmol) in dry THF
(100 mL) and the mixture was stirred for 20 min.
Then, compound IV (12.5 g, 40 mmol) was added
and the mixture was stirred for 10 h at room tem-
perature, followed by quenching the reaction by an
addition of H2O (10 mL), filtration, and evaporation
of the solvent under diminished pressure. The residue
was purified by flash chromatography using petroleum

632
Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
culated for C17H22NO4 (M + NH+4 ): 304.1544. Found:
304.1547.
at room temperature. The mixture was stirred for
3 h, quenched with H2O (10 mL) and the aqueous
layer was extracted with EtOAc. The extracts were
washed with brine, dried with Na2SO4, and the sol-
vent was removed under reduced pressure. The residue
was purified by flash chromatography using petroleum
ether/EtOAc (ϕr = 12 : 1) as eluent. Compound X
(3.6 g) was obtained as amorphous powder.
(1S,2S)-1-(4-(Benzyloxy)-3-methoxyphenyl)-1-
(tetrahydro-2H-pyran-2-yloxy)propan-2-ol (IX)
DHP (0.9 g, 10 mmol) and catalytic amount of
PPTS was added to a solution of compound VIII
(2.9 g, 10 mmol) in dry CH2Cl2 and the mixture was
stirred at room temperature for 10 h. The solvent was
evaporated under diminished pressure and the residue
was added to a solution of LiAlH4 (0.6 g, 15 mmol) in
dry THF (10 mL). The mixture was stirred at room
temperature for 24 h, quenched with H2O, filtered,
and concentrated under reduced pressure. The residue
was purified by flash chromatography using petroleum
ether/EtOAc (ϕr = 7 : 1) as eluent. Compound IX
(3.1 g) was obtained as colorless liquid in 93 % e.e.
[α]2D0 = −31.8◦ (c = 0.3, CHCl3). HRMS calculated for
C22H32NO5 (M + NH+4 ): 390.2273. Found: 390.2275.
(E)-2-Methoxy-1-(methoxymethoxy)-4-(prop-
1-enyl)benzene (XI)
A solution of BuLi in THF (1 M, 18 mL) was added
dropwise at 0◦C to a mixture of X (2.0 g, 10 mmol)
and ethyltriphenylphosphonium bromide (3.7 g, 10
mmol) in THF (20 mL) and the mixture was stirred
for 5 h followed by quenching of the reaction with 1 M
HCl (10 mL) at room temperature. The solvent was
evaporated under diminished pressure and the residue
was purified by flash chromatography using petroleum
ether/EtOAc (ϕr = 10 : 1) as eluent. Compound XI
(1.7 g) was obtained as colorless oil.
Perseal A (erythro-perseal) (II)
A mixture of (1S,2S)-IX (1.5 g, 4 mmol), vanillin
(0.62 g, 4 mmol), Ph3P (1.1 g, 4 mmol), and DEAD
(0.64 mL, 4 mmol) in anhydrous THF (20 mL)
was heated under reflux for 24 h in nitrogen atmo-
sphere. Then, the solvent was evaporated under re-
duced pressure, the residue was added to a solu-
tion of HCl in MeOH (1 M, 20 mL) and stirred at
room temperature for 8 h. The solution was neu-
tralized with a saturated aqueous NaHCO3 solu-
tion, concentrated under diminished pressure and the
residue was taken up in EtOAc. Organic phase was
separated, washed with H2O (20 mL), dried with
Na2SO4, and concentrated under reduced pressure.
To a stirred solution of the residue in MeOH (15
mL), 10 % Pd/C (70 mg) was added, a stream of
H2 was passed through and the mixture was stirred
for 8 h at room temperature followed by filtration
and evaporation of the solvent under reduced pres-
sure. The residue was purified by flash chromatog-
raphy using petroleum ether/EtOAc (ϕr = 7 : 1)
as eluent. Compound (1S,2R)-II (0.60 g) was ob-
tained as amorphous powder in 91 % e.e. (deter-
mination of the absolute configuration based on the
comparison with natural products). [α]2D0 = −29.8◦
(c = 0.2, CHCl3). HRMS calculated for C18H24NO6
(M + NH+4 ): 350.1605. Found: 350.1599. The data
were consistent with literature (Tsai et al., 1996).
(E)-Isoeugenol (XII)
A mixture of compound XI (1.5 g, 7 mmol) and 1
M HCl in MeOH (50 mL) was stirred at room temper-
ature for 8 h. The solution was neutralized with a satu-
rated aqueous NaHCO3 solution followed by evapora-
tion of the solvent under reduced pressure. The residue
was taken up in EtOAc, washed with H2O, dried with
Na2SO4, and concentrated under diminished pressure.
The residue was purified by flash chromatography us-
ing petroleum ether/EtOAc (ϕr = 8 : 1) as eluent.
Compound XII (1.0 g) was obtained as amorphous
powder.
(1S,2S)-1-(3-Methoxy-4-(methoxymethoxy)
phenyl)-1-(tetrahydro-2H-pyran-2-yloxy)
propan-2-ol (XIII)
To a stirred solution of compound IX (1.1 g, 3
mmol) in MeOH (10 mL), 10 % Pd/C (40 mg) was
added. A stream of H2 was passed through and the
mixture was stirred for 4 h at room temperature fol-
lowed by filtration and concentration under reduced
pressure. MOMCl (0.3 g, 3 mmol) was added to a
vigorously stirred mixture of the residue and K2CO3
(0.6 g, 4 mmol) in acetone (20 mL) in nitrogen atmo-
sphere and the mixture was stirred for 3 h at room
temperature. The reaction was quenched by an addi-
tion of H2O (10 mL) and the product was extracted
with EtOAc. The extract was washed with brine, dried
with Na2SO4, and the solvent was removed under
reduced pressure. The residue was purified by flash
chromatography using petroleum ether/EtOAc (ϕr =
9 : 1) as eluent. Compound XIII (0.9 g) was ob-
tained as amorphous powder. [α]2D0 = −28.7◦ (c =
3-Methoxy-4-(methoxymethoxy)benzaldehyde
(X)
A solution of MOMCl (1.6 g, 20 mmol) in THF
(15 mL) was added to a vigorously stirred solution
of vanillin (3.0 g, 20 mmol) and NaH (1.0 g, 40
mmol) in 60 mL of THF in the atmosphere of N2

Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
633
O
H3CO
BnO
CHO
OH
H3CO
HO
CHO
H3CO
BnO
OEt
i
iii
ii
III
IV
OH
H3CO
BnO
H3CO
BnO
H3CO
BnO
vi
OH
OH
v
OTs
iv
OH
OH
VII
V
VI
OH
OH
OTHP
OH
H3CO
HO
H3CO
BnO
H3CO
BnO
vii
viii
ix
O
O
x, xi
VIII
IX
H3CO
CHO
II
—
Fig. 1. Synthesis of perseal A ((1S,2R)-perseal) (II). Reaction conditions: i) BnCl, K2CO3, EtOH, reflux; ii) (Ph)3P CHCOOEt,
—
benzene, reflux; iii) LAH/AlCl3, THF; iv) AD-mix-α, MeSO2NH2, tert-BuOH/H2O, 0◦C; v) TsCl, pyridine, CH2Cl2, r.t.;
vi) K2CO3, MeOH, r.t.; vii) DHP, PPTS, CH2Cl2; viii) LAH, THF, r.t.; ix) vanillin, Ph3P, DEAD, THF, reflux; x) HCl,
MeOH, r.t.; xi) 10 % Pd/C, H2, r.t.
0.2, CHCl3). HRMS calculated for C17H30NO6 (M +
NH+4 ): 344.2068. Found: 344.2073.
IV with LAH afforded the corresponding unsatu-
rated alcohol (E)-V in high yield. It is interesting
that treatment of compound V with AD-mix-α af-
forded compound (1S,2S)-VI of the threo configura-
tion in 93 % e.e. (Sharpless et al., 1992). This re-
action represents the dihydroxylation of double bond
in V to obtain two chiral centers at the same time.
Treatment of (1S,2S)-VI (threo isomer) with TsCl in
pyridine provided (1S,2S)-VII (threo isomer). Due to
the steric hindrance, only primary hydroxyl group of
(1S,2S)-VI (threo isomer) was tosylated. Ring clo-
sure of (1S,2S)-VI (threo isomer) was promoted by
K2CO3 in methanol, generating oxirane (1S,2S)-VIII
(threo isomer). Hydroxyl group of VIII was protected
by DHP to afford the corresponding ether, followed
by oxirane reduction using LiAlH4 to give (1S,2S)-
IX (threo isomer). Subsequent Mitsunobu reaction of
IX and vanillin resulted in the inversion of the con-
figuration (S to R, > 92 % e.e.) at the C-8 atom af-
fording thus the product with erythro configuration
(Mitsunobu, 1981). Finally, the THP group was re-
moved with 0.3 M HCl in MeOH and the benzyl group
was cleaved by hydrogenation with a 10 % Pd/C cat-
alyst to afford perseal A (II) as a single erythro isomer
((1S,2R)-configuration).
Machilin C (erythro-machilin) (I)
A mixture of (1S,2S)-XIII (0.7 g, 2 mmol),
isoeugenol (XII ) (0.3 g, 2 mmol), triphenylphosphine
(0.6 g, 2 mmol), and diethyl azodicarboxylate (0.3 mL,
2 mmol) in anhydrous THF (20 mL) was heated un-
der reflux for 24 h in nitrogen atmosphere followed by
concentration under reduced pressure. A solution of
HCl in MeOH (1 M, 20 mL) was added to the residue
and the mixture was stirred at room temperature for
8 h. The solution was neutralized with a saturated
aqueous NaHCO3 solution and concentrated under re-
duced pressure. The residue was taken up in EtOAc,
washed with H2O, dried over Na2SO4, and the sol-
vent was evaporated under diminished pressure. The
residue was purified by flash chromatography using
petroleum ether/EtOAc (ϕr = 8 : 1) as eluent. Com-
pound I (0.5 g) was obtained as amorphous powder in
92 % e.e. (determination of the absolute configuration
was based on the comparison with natural products).
[α]2D0 = −18.4◦ (c = 0.1, CHCl3). HRMS calculatd for
C20H28NO5 (M + NH+4 ): 362.1962. Found: 362.1967.
The data are in agreement with those reported by Shi-
momura et al. (1987).
As shown in Fig. 2, the hydroxyl group in vanillin
was protected by MOMCl to give compound X. The
—
Wittig reaction of X and (Ph) P CHCH afforded
—
3
3
Results and discussion
(E)-XI followed by the cleavage of the MOM group
using HCl to obtain the intermediate (E)-isoeugenol
(XII ).
The benzyl group of compound IX was removed
to give the corresponding phenol. Its hydroxyl group
was protected by MOMCl to afford compound XIII.
The Mitsunobu reaction of threo-XIII and XII gave
As shown in Fig. 1, synthesis of the target com-
pound started from vanillin. Treatment of vanillin
with benzyl chloride afforded compound III. The Wit-
—
tig reaction of compound III and (Ph) P CHCOOEt
—
3
gave the unsaturated ester (E)-IV. Reduction of (E)-

634
Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
H3CO
HO
CHO
H3CO
CHO
H3CO
H3CO
HO
i
ii
iii
MOMO
MOMO
X
X I
X II
OTHP
OH
OTHP
OH
OH
2
5
9
H3CO
BnO
iv
v
7
1
H3CO
3
4
vi
H3CO
HO
8
5'
vii
6
O
MOMO
6'
7'
4'
H3CO
IX
X III
9'
1'
3'
8'
2'
I
—
Fig. 2. Synthesis of machilin C ((1S,2R)-machilin) (I). Reaction conditions: i) MOMCl, NaH, THF; ii) Ph3P CHCH3, THF; iii)
—
HCl, MeOH, r.t.; iv) 10 % Pd/C, H2, r.t.; v) MOMCl, K2CO3, acetone; vi) XII, Ph3P, DEAD, THF, reflux; vii) HCl,
MeOH, r.t.
Table 1. Characterization data of the prepared compounds
wi(calc.)/%
wi(found)/%
Compound
Formula
Mr
Yield/%
M.p./◦C
C
H
I
II
C20H24O5
C18H20O6
C15H14O3
C19H20O4
C17H18O3
C17H20O5
C24H26O7S
C17H18O4
C22H28O5
C10H12O4
C12H16O3
C10H12O2
C17H26O6
344.40
332.35
242.27
312.36
270.32
304.34
458.52
286.33
372.46
196.20
208.26
164.20
326.39
69.70
69.75
65.04
65.05
74.41
74.36
73.05
73.06
75.55
75.53
67.08
67.09
62.82
62.87
71.30
71.31
70.95
70.94
61.20
61.22
69.26
69.21
73.13
73.15
62.51
62.56
7.02
7.02
6.06
6.07
5.85
5.82
6.45
6.45
6.72
6.71
6.60
6.62
5.70
5.72
6.34
6.34
7.59
7.58
6.15
6.16
7.79
7.74
7.35
7.37
7.98
8.03
74
45
92
72
88
94
83
95
82
93
82
87
90
–
–
III
IV
V
62
70
79
153
–
VI
VII
VIII
IX
X
–
–
–
XI
XII
XIII
–
–
–
a product with the erythro configuration. Finally, the
MOM and THP groups were cleaved by HCl in MeOH
and machilin C (I ) was obtained as a single erythro
isomer ((1S,2R)-configuration).
8-O-4ꢀ neolignans to give machilin C and its analogue
perseal A was developed. With cheap materials, short
experimental procedures, mild conditions, and simple
operations, the route is supposed to have more poten-
tial value in future.
Conclusions
Acknowledgements. This work was financially supported
by the Taishan Scholar Project of the Shandong Province
(NO.2005011036), Specialized Research Fund for the Doctoral
In summary, a chiral synthetic method of erythro-

Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
Table 2. Spectral data of the prepared compounds
635
Compound
Spectral data
IR, ν˜/cm−1: 3540, 2963, 2862, 1612, 1520, 1505, 1382, 1028
I
1H NMR (500 MHz, CDCl3), δ: 1.18 (d, 3H, J = 6.5 Hz, H-9), 1.87 (d, 3H, J = 7.0 Hz, H-9ꢀ), 3.87 (s, 3H, OCH3),
3.91 (s, 3H, OCH3), 4.35 (m, 1H, H-8), 4.84 (d, 1H, J = 2.9 Hz, H-7), 6.18 (m, 1H, H-8ꢀ), 6.35 (m, 1H, H-7ꢀ),
6.75–7.10 (m, 6H, ArH) 13C NMR (125 MHz, CDCl3), δ: 13.4 (C-9), 18.3 (C-9ꢀ), 56.0 (2 × OCH3), 73.6 (C-8),
82.4 (C-7), 108.9 (C-2), 109.4 (C-2ꢀ), 113.9 (C-5), 119.0 (C-6ꢀ), 119.1 (C-5ꢀ), 119.9 (C-6), 125.0 (C-8ꢀ), 130.5 (C-7ꢀ),
131.9 (C-1ꢀ), 133.7 (C-1), 144.8 (C-4), 145.6 (C-3ꢀ), 146.5 (C-3), 151.5 (C-4ꢀ)
EIMS, m/z (Ir/%): 344 (2.6) (M+), 192 (25.7), 164 (3.8), 137 (4.6), 91 (100)
II
IR, ν˜/cm−1: 3420, 2955, 2850, 1675, 1590, 1510
1H NMR (500 MHz, CDCl3), δ: 1.22 (d, 3H, J = 6.5 Hz, Me-8), 3.92 (s, 3H, OMe-3), 3.95 (s, 3H, OMe-3ꢀ), 4.65
(m, 1H, H-8), 4.91 (d, 1H, J = 4.0 Hz, H-7), 6.85–7.05 (m, 3H, ArH), 7.07–7.46 (m, 3H, ArHꢀ), 9.86 (s, 1H, CHO)
13C NMR (125 MHz, CDCl3), δ: 13.5 (Me-9), 56.0 (OMe-3), 56.1 (OMe-3ꢀ), 75.2 (C-7), 81.1 (C-8), 109.3 (C-2),
110.1 (C-6ꢀ), 114.2 (C-5), 115.4 (C-5ꢀ), 119.6 (C-6), 126.3 (C-2ꢀ), 131.0 (C-1), 131.4 (C-1ꢀ), 145.7 (C-4), 146.5 (C-3ꢀ),
151.2 (C-3), 152.8 (C-4ꢀ), 190.9 (CHO)
EIMS, m/z (Ir/%): 332 (5.2) (M+), 180 (85.6), 165 (12.4), 151 (100), 135 (73.5)
III
IV
1H NMR (200 MHz, DMSO-d6), δ: 3.83 (s, 3H, OCH3), 5.17 (s, 2H, ArCH2O), 7.01–7.67 (m, 8H, ArH), 9.87 (s,
1H, CHO)
EIMS, m/z (Ir/%): 242 (14.3) (M+), 214 (3.2), 91 (100), 65 (13.5), 51 (5.2)
1H NMR (200 MHz, CDCl3), δ: 1.44 (t, 3H, J = 7.2 Hz, COCH2CH3), 3.98 (s, 3H, OCH3), 4.26 (q, 2H, J = 7.2
—
Hz, COCH2CH3), 5.10 (s, 2H, ArCH2O), 6.25 (d, 1H, J = 14.2 Hz, ArCH CH), 6.70–7.52 (m, 8H, ArH), 7.63 (d,
—
—
1H, J = 14.2 Hz, ArCH CH)
—
EIMS, m/z (Ir/%): 312 (15) (M+), 267 (12), 221 (1.2), 153 (8), 91 (100)
V
1H NMR (300 MHz, CDCl3), δ: 3.88 (s, 3H, OCH3), 4.28 (d, 2H, J = 6.0 Hz, CH2OH), 4.61 (s, 1H, OH), 5.13
—
—
(s, 2H, ArCH2O), 6.24 (dt, 1H, J = 6.0 Hz, J = 15.9 Hz, ArCH CH), 6.53 (d, 1H, J = 15.9 Hz, ArCH CH),
—
—
6.68–7.44 (m, 8H, ArH)
EIMS, m/z (Ir/%): 270 (25) (M+), 179 (12), 151 (8), 119 (18), 91 (100)
IR, ν˜/cm−1: 3410, 2935, 2840, 1655, 1516, 1460, 1155, 990
VI
1H NMR (300 MHz, CDCl3), δ: 3.40 (dd, 1H, J = 3.0, 9.4 Hz, CH2OH), 3.47 (dd, 1H, J = 3.0 Hz, J = 9.4 Hz,
CH2OH), 3.60–3.73 (m, 1H, CHOHCH2OH), 3.82 (s, 3H, OCH3), 4.61 (d, J = 6.5 Hz, 1H, ArCHOH), 5.10 (s, 2H,
ArCH2OAr), 6.86–7.04 (m, 3H, ArH), 7.31–7.51 (m, 5H, ArH)
EIMS, m/z (Ir/%): 304 (0.9) (M+), 286 (5), 243 (17), 153 (24), 91 (100)
VII
IR, ν˜/cm−1: 3420, 2941, 2845, 1641, 1520, 1422, 1318, 1235, 1102, 1023
1H NMR (300 MHz, CDCl3), δ: 2.44 (s, 3H, ArCH3), 3.90 (s, 3H, ArOCH3), 3.84–3.96 (m, 1H, CHOHCH2OTs),
3.98–4.11 (m, 2H, CH2OTs), 4.60 (d, 1H, J = 6.0 Hz, ArCHOH), 5.14 (s, 2H, ArCH2OAr), 6.72–7.76 (m, 12H, ArH)
13C NMR (75 MHz, CDCl3), δ: 21.6 (ArCH3), 56.0 (OCH3), 70.3 (CH2OTs), 70.9 (CHOHCH2OTs), 73.4
(ArCH2OAr), 73.7 (ArCHOHCH), 109.9, 113.7, 118.8, 127.2, 127.2, 127.9, 127.9, 128.6, 128.6, 129.9, 129.9, 132.5,
132.5, 136.9, 136.9, 146.1, 148.1, 149.8
EIMS, m/z (Ir/%): 458 (2.4) (M+), 286 (1.2), 268 (0.7), 243 (4.8), 123 (7.8), 91 (100)
VIII
IX
IR, ν˜/cm−1: 3450, 2983, 2936, 2840, 1732, 1604, 1592, 1512, 1465, 1262, 1140, 1027, 916
1H NMR (300 MHz, CDCl3), δ: 2.80–2.89 (m, 2H, CHOCH2), 3.16–3.25 (m, 1H, CHCH2O), 3.97 (s, 3H, OCH3),
4.43 (d, 1H, J = 5.8 Hz, ArCHOHCH), 5.17 (s, 2H, ArCH2OAr), 6.87–7.45 (m, 8H, ArH)
13C NMR (75 MHz, CDCl3), δ: 45.6 (CHCH2O), 56.2(OMe-3), 56.7 (CHCH2O), 71.3 (ArCH2OAr), 74.8
(ArCHOHCH), 109.3, 113.9, 121.5, 126.7, 127.2, 127.2, 127.9, 128.5, 128.5, 137.1, 147.3, 149.6
EIMS, m/z (Ir/%): 286 (5) (M+), 243 (0.7), 165 (0.4), 123 (0.2), 91 (100)
IR, ν˜/cm−1: 3418, 2936, 2869, 1593, 1513, 1457, 1418, 1380, 1263, 1226, 1137, 1075, 1028, 809
1H NMR (300 MHz, CDCl3), δ: 1.00 (d, 3H, J = 7.0 Hz, OHCHCH3), 1.44–1.72 (m, 6H, CH2), 3.20 (m, 1H,
CH2CH2O), 3.45 (m, 1H, CH2CH2O), 3.89 (s, 3H, OCH3), 3.84–4.05 (m, 1H, CHOHCH3), 4.16 (d, 1H, J = 7.5 Hz,
ArCHOTHP), 4.84 (s, 1H, OCHO), 5.14 (s, 2H, ArCH2OAr), 6.82–6.90 (m, 3H, ArH), 7.30–7.44 (m, 5H, ArH)
13C NMR (75 MHz, CDCl3), δ: 18.2 (CH2CH2), 19.3 (HOCHCH3), 25.2 (CH2CH2), 30.5 (CH2CH2), 55.9 (CH3O),
62.4 (CH2OCH), 71.0 (CH3CHOH), 71.1 (ArCH2O), 85.7 (ArCHOTHP), 100.0 (OCHO), 110.8, 113.4, 119.7, 127.3,
127.3, 127.8, 128.5, 128.5, 133.3, 137.1, 147.6, 149.3
EIMS, m/z (Ir/%): 372 (0.4) (M+), 328 (1.6), 288 (0.3), 271 (0.6), 243 (37), 91 (98), 85 (100)
X
1H NMR (500 MHz, CDCl3), δ: 3.50 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 5.40 (s, 2H, OCH2O), 7.19–7.46 (m, 3H,
ArHꢀ), 9.85 (s, 1H, CHO)
EIMS, m/z (Ir/%): 196 (24.5) (M+), 166 (12.7), 84 (5.6), 45 (100)
XI
1H NMR (500 MHz, CDCl3), δ: 1.87 (d, 3H, J = 6.4 Hz, CH3), 3.52 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), 5.25 (s,
—
—
2H, OCH2O), 5.95–6.22 (m, 1H, ArCH CH), 6.35 (d, 1H, J = 17.0 Hz, ArCH CH), 6.85–7.11 (m, 3H, ArH)
—
—
EIMS, m/z (Ir/%): 208 (28) (M+), 178 (42), 163 (35), 107 (54), 91 (62), 45 (100)
XII
IR, KBr/cm−1: 3450, 3017, 2962, 2850, 1696, 1675, 1513, 1427, 1267, 1207, 1034, 963
H NMR (500 MHz, CDCl3), δ: 1.84 (d, 3H, J = 6.5 Hz, CH3), 3.82 (s, 3H, OCH3), 6.08 (m, 1H, ArCH CH), 6.30
1
—
—
—
(d, 1H, J = 15.0 Hz, ArCH CH), 6.79–6.87 (m, 3H, ArH)
—
13
—
—
C NMR (125 MHz, CDCl3), δ: 18.3 (CH3), 55.8 (OCH3), 107.9, 114.4, 119.2, 123.2 (ArCH CH), 130.6, 130.7
—
(ArCH CH), 144.7, 146.4
—
EIMS, m/z (Ir/%): 164 (100) (M+), 149 (53), 131 (22), 103 (12), 91 (18), 55 (13)

636
Y. Xia, W. Wang/Chemical Papers 64 (5) 630–636 (2010)
Table 2. (continued)
Compound
Spectral data
XIII
IR, ν˜/cm−1: 3452, 2943, 2852, 1602, 1513, 1467, 1382, 1263, 1135, 1028, 902
1H NMR (500 MHz, CDCl3), δ: 1.06 (d, 3H, J = 7.0 Hz, OHCHCH3), 1.47–1.78 (m, 6H, CH2), 3.20 (m, 1H,
CH2CH2O), 3.43 (m, 1H, CH2CH2O), 3.52 (s, 3H, OCH3), 3.85–4.02 (m, 4H, CHOHCH3, OCH3), 4.15 (d, 1H, J
= 8.0 Hz, ArCHOTHP), 4.87 (s, 1H, OCHO), 5.29 (s, 2H, CH3OCH2OAr), 6.85–7.10 (m, 3H, ArH)
13C NMR (125 MHz, CDCl3), δ: 17.8 (CH2CH2), 19.5 (HOCHCH3), 24.9 (CH2CH2), 31.2 (CH2CH2), 55.7 (CH3O),
56.9 (CH3OCH2Ar), 62.4 (CH2OCH), 71.8 (CH3CHOH), 82.7 (ArCHOTHP), 95.8 (CH3OCH2Ar), 100.2 (OCHO),
111.8, 116.5, 120.2, 123.8, 144.3, 149.7
EIMS, m/z (Ir/%): 326 (3.8) (M+), 294 (12.3), 280 (4.5), 263 (23.1), 91 (100)
Program of Higher Education of China (No. 20093719120004),
and the Open Foundation of Chemical Engineering Subject,
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