First enantioselective synthesis of the neolignans Rhaphidecursinol A and Virolongin B

Article abstract of DOI:10.1002/jccs.200400144

The enantioselective synthesis of the neolignans Rhaphidecursinol A and Virolongin B is reported for the first time. The key reactions in the synthesis were Sharpless asymmetric dihydroxylation and Mitsunobu reaction. The absolute configuration of Rhaphidecursinol A was confirmed.

Full text of DOI:10.1002/jccs.200400144

Journal of the Chinese Chemical Society, 2004, 51, 969-974
969
First Enantioselective Synthesis of the Neolignans Rhaphidecursinol A
and Virolongin B
Xinfeng Rena (
Ying Sua (
Xinfu Pana* (
), Xuegong Shea (
), Kun Penga (
),
),
), Xingang Xiea (
) and Hongbin Zhangb (
)
aDepartment of Chemistry, State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P. R. China
bSchool of Pharmacy, Yunnan University, Kunming, Yunnan 650091, P. R. China
The enantioselective synthesis of the neolignans Rhaphidecursinol A and Virolongin B is reported for the
first time. The key reactions in the synthesis were Sharpless asymmetric dihydroxylation and Mitsunobu reac-
tion. The absolute configuration of Rhaphidecursinol A was confirmed.
Keywords: Enantioselective; Synthesis; Neolignan; Rhaphidecursinol A; Virolongin B.
INTRODUCTION
Lignans and neolignans are an important group of natu-
cursiva7 and was determined to be an 8-O-4¢ neolignan.
Virolongin B 2, an analog of 1, was first isolated from nut-
meg,8 which are the seeds of the fruit of the trees, Myristica
fragrans Houtt, Licaria aurea,9 Licaria chrysophylla,10 and
Aristolochia birostris.11 These plants have been used in folk
medicine for many years for their alleged abortifacient, nar-
cotic, and therapeutic properties. We noticed that neither
their absolute configurations nor their asymmetric syntheses
have yet been reported. Herein, we wish to report the first
asymmetric syntheses of Rhaphidecursinol A and Virolongin
B, and the absolute configuration of Rhaphidecursinol A de-
duced from its optical rotation.
ral products consisting of two phenylpropane monomers
linked through carbon-carbon or carbon-oxygen bonds, and
the syntheses of neolignans have already been developed in
our laboratory.1 Within the great structural variety of neo-
lignans, the 8-O-4¢-type represents a small group. Many
show strong activity against the penetration of cercaria of
Schistosoma mansoni,2 inhibition of the growth of silkworm
larvae,3 and antileukemic activity in rats.4 In order to study
the relationship of structure and biological activity, several
8-O-4¢ neolignans have been synthesized.5 But these methods
were racemic synthesis routes and led to the mixture of
erythro and threo isomers. An asymmetric synthesis of 8-
O-4¢ neolignans was reported in 1996, but equal amounts of
two diastereoisomers were obtained finally.6 Now we report
an asymmetric synthetic approach to 8-O-4¢ neolignans.
Rhaphidecursinol A 1, an optically active substance
with varying degrees of antimalarial activity, was isolated
from the dried leaves and stems of Rhaphidophora de-
RESULTS AND DISCUSSION
As shown in Scheme I, 2,6-Dimethoxyphenol 3 was
easily protected with allyl bromide to give 2-(allyloxy)-1,3-
dimethoxybenzene 4, which underwent Claisen rearrange-
ment to give 3-(4-hydroxy-3,5-dimethoxyphenyl)-1-propene
5. Methylation of the hydroxy group afforded 3-(3,4,5-tri-
7'
9'
2'
MeO
OMe
MeO
1'
6'
OMe
OMe
8'
MeO
MeO
MeO
4
6
O
4'
O
8
OMe
1
MeO
9
2
7
OH
1
2
* Corresponding author. E-mail: panxf@lzu.edu.cn

970 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ren et al.
Scheme I
OMe
OH
OAllyl
OMe
MeO
MeO
MeO
MeO
MeO
HO
MeO
OMe
MeO
iv
OH
iii
ii
i
OH
OMe
6
OMe
5
3
(2S)-7
4
MeO
O
MeO
OMe
OMe
OMe
MeO
MeO
MeO
MeO
MeO
OH
O
v
vi
vii
OMe
OMe
MeO
OBenzoyl
OBenzoyl
MeO
OH
(2R)-1
(2S)-8
(2R)-9
MeO
OMe
OMe
OMe
MeO
MeO
MeO
MeO
MeO
O
vii
viii
v
vi
O
OH
6
(2R)-8
OMe
OH
OMe
OH
MeO
OBenzoyl
(2S)-1
(2R)-7
(2S)-9
MeO
OMe
OMe
OMe
MeO
MeO
MeO
MeO
MeO
OH
OH
O
xi
ix
x
(2S)-7
(2R)-7
OMe
(2S)-2
MeO
OTs
(2S)-10
(2R)-11
MeO
OMe
OMe
OMe
MeO
MeO
MeO
MeO
MeO
MeO
ix
x
xi
O
OH
OH
OMe
(2R)-2
OTs
(2S)-11
(2R)-10
Reagents and conditions: (i) allyl bromide, K2CO3, acetone, rt, 24 h, 94%; (ii) 200 °C, 2 h, 92%; (iii) MeI, K2CO3,
acetone, rt, 24 h, 96%; (iv) AD-mix-a, t-BuOH, H2O, 0 °C, 20 h, 88%; (v) Et3N, benzoyl chloride, CH2Cl2, -10 °C, 6
h, 82%; (vi) DIAD, Ph3P, THF, 5, rt, 24 h, 52%; (vii) K2CO3, methanol and H2O (9:1), rt, 6 h, 72%; (viii) AD-mix-b,
t-BuOH, H2O, 0 °C, 20 h, 90%; (ix) Et3N, TsCl, CH2Cl2, 0 °C, 6 h, 85%; (x) LAH, THF, 4 h, 82%; (xi) DIAD, Ph3P,
THF, 5, rt, 24 h, 57%.
methoxyphenyl)-1-propene 6. Sharpless asymmetric dihy-
droxylation of 6 with AD-mix-a yielded compound 7. De-
pending on the experimental result of K. B. Sharpless,12 the
absolute configuration of compound 7 could be determined
as S. Treatment of (2S)-7 with benzoyl chloride provided
(2S)-8, which was converted into (2R)-9 using the Mitsunobu
reaction13 with 5 as nucleophile. According to the mechanism
of Mitsunobu reaction, in this reaction the absolute configu-
ration of C-8 in 8 was inverted completely by the SN2-type
nucleophilic displacement with 5. The benzoyl group on
(2R)-9 was removed with potassium carbonate to give (2R)-1.
Compound (2S)-1 was obtained in a similar manner using
AD-mix-b in the Sharpless reaction. Protecting (2S)-7 with
TsCl, followed by reduction with LAH, and the Mitsunobu
reaction13 with 5, yielded (2S)-2. Compound (2R)-2 was ob-
tained in a similar manner using (2R)-7.
In summary, here we demonstrated a high enantio-
selective synthesis of 8-O-4¢ neolignans Rhaphidecursinol A
and Virolongin B. Therefore the route could be used for
asymmetric synthesis of both neolignans. All spectral data
were in agreement with those in the literature.7-10 Compound
(2R)-1 has an optical rotation of +3.1, which is in good agree-
ment with the literature value of +2.61 for Rhaphidecursinol
A.6

Asymmetry Synthesis of Two Neolignans
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 971
EXPERIMENTAL SECTION
mmol) was added and stirred overnight. The solvent was
evaporated, 3N HCl (10 mL) was added, and the mixture was
extracted with EtOAc. The organic fraction was washed with
brine, dried over Na2SO4 and the solvent removed. Flash
chromatography of the residue using petroleum ether/ethyl
acetate (12:1, v/v) as eluant gave a colorless oil 6 (2.06 g,
96%): 1H NMR (200 MHz, CDCl3) d 3.34 (d, 2H, J = 6.6 Hz),
3.84 (s, 9H), 5.09 (dd, 1H, J = 9.6, 1.2 Hz), 5.11 (dd, 1H, J =
17.2, 1.6 Hz), 5.98 (m, 1H), 6.42 (s, 2H). MS (EI), m/z 208
(M+), 193, 165, 133, 121, 105, 91, 77.
Melting points were measured on a Kofler apparatus
and were uncorrected. The 1H NMR and 13C NMR data were
recorded with a Bruker AM-80, Avance-200 MHz and Avance-
400 MHz spectrometers. Chemical shifts (d) are reported in
ppm relative to TMS. Mass spectra were recorded on a
ZAB-HS spectrometer. Optical rotations were determined on
a Perkin Elmer 341 polarimeter. Chiral analysis was per-
formed on a Varian Dynamax SD-300 using a chiralcel col-
umn CDMPC (150 ´ 4.6 mm D) with hexane/isopropyl alco-
hol as eluant. IR spectra were recorded on a Nicolet FT-170
SX spectrometer. Flash column chromatography was per-
formed on silica gel (200-300 mesh) eluting with petroleum
ether/ethyl acetate. TLC inspections were performed on sil-
ica gel GF254 plates with petroleum ether/ethyl acetate as
eluant, unless otherwise state.
(S)-3-(3,4,5-Trimethoxyphenyl)-1,2-propanediol [(2S)-7]
To a stirred solution of t-BuOH (20 mL) and H2O (20
mL), AD-mix-a (5.6 g) was added. The mixture was stirred at
room temperature until both phases were clear, and cooled to
0 °C. Compound 6 (832 mg, 4 mmol) was added, and the mix-
ture stirred vigorously at 0 °C until TLC revealed complete
consumption of 6. The reaction was quenched at 0 °C by addi-
tion of Na2SO3 (6 g), warmed to room temperature and stirred
for 0.5 h. After extraction with ethyl acetate, the organic frac-
tion was washed with water and dried over Na2SO4. The sol-
vent was removed and flash chromatography of the residue
using petroleum ether/ethyl acetate (1:2, v/v) as eluant gave a
white powder (2S)-7 (852 mg, 92% e.e., 88%) (Chiralcel col-
umn CDMPC, n-hexane:isopropyl alcohol, 50:1, 1 mL/min,
25 °C, retention times 17.6 min). M.p. 73-75 °C. [a]2D5 -4 (c
2.5, CHCl3). 1H NMR (200 MHz, CDCl3) d 2.60 (dd, 1H, J =
13.6, 7.2 Hz), 2.75 (dd, 1H, J = 13.8, 6.0 Hz), 3.51 (dd, 1H, J
= 11.8, 3.8 Hz), 3.69 (dd, 1H, J = 11.0, 3.0 Hz), 3.82 (s, 9H),
3.97 (m, 1H), 6.43 (s, 2H). MS (EI), m/z 242 (M+), 211, 181,
167, 151, 91, 65.
2-(Allyloxy)-1,3-dimethoxybenzene (4)
To a solution of 3 (4 g, 0.026 mol) in acetone (60 mL)
was added potassium carbonate (4.3 g, 0.031 mol) and allyl
bromide (4.72 g, 0.039 mol). The suspension was stirred
overnight. The solvent was removed, 3N HCl (15 mL) was
added, and the mixture was extracted with EtOAc. The or-
ganic fraction was washed with brine, dried over Na2SO4, and
the solvent removed under reduced pressure. Flash chroma-
tography of the residue using petroleum ether/ethyl acetate
(15:1, v/v) as eluant afforded 4 (4.74 g, 94%) as a colorless
oil: 1H NMR (200 MHz, CDCl3) d 3.84 (s, 6H), 4.52 (d, 2H, J
= 6.0 Hz), 5.18 (dd, 1H, J = 10.4, 1.0 Hz), 5.30 (dd, 1H, J =
17.2, 1.6 Hz), 6.14 (m, 1H), 6.54-7.02 (m, 3H). MS (EI), m/z
194 (M+), 153, 125, 110, 93.
(R)-3-(3,4,5-Trimethoxyphenyl)-1,2-propanediol [(2R)-7]
Compound (2R)-7 was prepared in an analogous man-
ner to (2S)-7, using 6 (850 mg, 4.09 mmol) and AD-mix-b
(5.7 g) to give a white powder (890 mg, 93% e.e., 90%). M.p.
80-83 °C. [a]2D5 +5 (c 1.7, CHCl3). Other spectral data were
the same as for (2S)-7.
3-(4-Hydroxy-3,5-dimethoxyphenyl)-1-propene (5)
Compound 4 (2.5 g, 12.9 mmol) was heated to 200 °C
for 2 h. Flash chromatography of the residue using petroleum
ether/ethyl acetate (7:1, v/v) as eluant afforded 5 (2.3 g, 92%)
as a colorless oil. 1H NMR (200 MHz, CDCl3) d 3.33 (d, 2H, J
= 6.6 Hz), 3.88 (s, 6H), 5.08 (dd, 1H, J = 10.2, 1.0 Hz), 5.10
(dd, 1H, J = 17.6, 1.6 Hz), 5.44 (s, 1H), 5.98 (m, 1H), 6.42 (s,
2H). MS (EI), m/z 194 (M+), 179, 153, 131, 91, 77.
(S)-3-(3,4,5-Trimethoxyphenyl)-1-O-benzoyl-1,2-pro-
panediol [(2S)-8]
To a solution of compound (2S)-7 (0.55 g, 2.27 mmol)
in dichloromethane (20 mL) at -10 °C under N2, triethyl-
amine (0.34 g, 3.4 mmol) was added. After stirring the reac-
tion mixture for 15 min, benzoyl chloride (0.34 g, 2.39 mmol)
was added. The mixture was stirred at -10 °C for 6 h, the sol-
3-(3,4,5-Trimethoxyphenyl)-1-propene (6)
To a solution of 5 (2 g, 10.3 mmol) in acetone (50 mL),
potassium carbonate (1.71 g, 12.4 mmol) was added. The sus-
pension was stirred for 10 min, iodomethane (2.2 g, 15.5

972 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ren et al.
vent was removed, and water (10 mL) was added to the resi-
due. The mixture was extracted with ethyl acetate, the or-
ganic phase was washed with brine, dried over Na2SO4, and
concentrated in vacuo. Flash chromatography of the residue
using petroleum ether/ethyl acetate (5:1, v/v) as eluant
yielded (2S)-8 (0.65 g, 82%) as a white powder. M.p. 76-79
°C. [a]2D5 +3.3 (c 2.1, CHCl3). 1H NMR (200 MHz, CDCl3) d
2.78 (dd, 1H, J = 13.4, 7.0 Hz), 2.90 (dd, 1H, J = 13.8, 6.2
Hz), 3.83 (s, 9H), 4.24 (m, 1H), 4.37 (dd, 1H, J = 12.0, 3.8
Hz), 4.42 (dd, 1H, J = 11.4, 3.0 Hz), 6.47 (s, 2H), 7.27-8.08
(m, 5H). MS (EI), m/z 346 (M+), 328, 223, 181, 167, 105, 77.
(R)-3-(3,4,5-trimethoxyphenyl)-2-O-(4-allyl-2,6-dimethoxy-
phenyl)-1,2-propanediol [(2R)-1]
Compound (2R)-9 (104 mg, 0.2 mmol) was dissolved in
methanol (9 mL) and water (1 mL), potassium carbonate (82
mg, 0.6 mmol) was added and the suspension was stirred for 6
h at room temperature. The solvent was evaporated, water (15
mL) added and the mixture was extracted with ethyl acetate.
The organic layer was washed with brine, dried over Na2SO4
and the solvent removed. Flash chromatography of the resi-
due using petroleum ether/ethyl acetate (4:1, v/v) as eluant
gave a colorless oil (2R)-1 (60 mg, 72%). [a]2D5 +3.1 (c 1.5,
MeOH). IR (KBr), u/cm-1: 3508, 2936, 2838, 1590, 1504,
1460, 1422, 1331, 1239, 1127 and 1015. 1H NMR (400 MHz,
CDCl3) d 2.99 (dd, 1H, J = 13.6, 8.3 Hz), 3.24 (dd, 1H, J =
13.6, 5.4 Hz), 3.35 (d, 2H, J = 6.6 Hz), 3.45 (dd, 1H, J = 12.4,
3.8 Hz), 3.59 (dd, 1H, J = 12.4, 2.3 Hz), 3.83 (s, 6H), 3.86 (s,
9H), 4.22 (m, 1H), 5.11 (dq, 1H, J = 10.6, 1.2 Hz), 5.13 (dq,
1H, J = 17.6, 1.6 Hz), 5.98 (m, 1H), 6.44 (s, 2H), 6.54 (s, 2H).
13C NMR (100 MHz, CDCl3) d 38.1, 40.5, 56.1, 60.8, 62.4,
84.1, 105.6, 106.5, 116.1, 134.2, 136.2, 137.0, 152.9, 153.2.
MS (EI), m/z 418 (M+), 326, 224, 207, 194, 181, 91, 77.
HRFABMS m/z 436.2337 (C23H34O7N requires 436.2330).
(R)-3-(3,4,5-Trimethoxyphenyl)-1-O-benzoyl-1,2-pro-
panediol [(2R)-8]
Compound (2R)-8 was prepared in an analogous man-
ner to (2S)-8, using (2R)-7 (700 mg, 2.89 mmol), triethyl-
amine (438 mg, 4.4 mmol) and benzoyl chloride (427 mg,
3.04 mmol) to give a white powder (850 mg, 85%). M.p.
79-81 °C. [a]2D5 -3.5 (c 3.2, CHCl3). Other spectral data were
the same as for (2S)-8.
(R)-3-(3,4,5-Trimethoxyphenyl)-1-O-benzoyl-2-O-(4-allyl-
2,6-dimethoxyphenyl)-1,2-propanediol [(2R)-9]
To a solution of 5 (141 mg, 0.73 mmol) and DIAD (147
mg, 0.73 mmol) in dry THF at room temperature under nitro-
gen a solution of PPh3 (191 mg, 0.73 mmol) and (2S)-8 (210
mg, 0.6 mmol) in dry THF (10 mL) was added dropwise. Af-
ter stirring the mixture overnight, the solvent was removed.
Flash chromatography of the residue using petroleum ether/
ethyl acetate (7:1, v/v) as eluant yielded a colorless oil (2R)-9
(S)-3-(3,4,5-trimethoxyphenyl)-2-O-(4-allyl-2,6-dimethoxy-
phenyl)-1,2-propanediol [(2S)-1]
Compound (2S)-1 was prepared in an analogous man-
ner to (2R)-1, using (2S)-9 (150 mg, 0.29 mmol) and potas-
sium carbonate (119 mg, 0.86 mmol) to give a colorless oil
(89 mg, 74%). [a]2D5 -2.8 (c 2.0, MeOH). Other spectral data
were the same as for (2R)-1.
1
(164 mg, 52%). [a]2D5 +5.2 (c 3.2, CHCl3). H NMR (200
MHz, CDCl3) d 3.07 (dd, 1H, J = 13.8, 7.2 Hz), 3.26 (dd, 1H,
J = 14.0, 6.0 Hz), 3.33 (d, 2H, J = 6.4 Hz), 3.69 (s, 6H), 3.82
(s, 9H), 4.40 (dd, 1H, J = 12.2, 3.6 Hz), 4.43 (dd, 1H, J = 12.2.
2.6 Hz), 4.64 (m, 1H), 5.09 (dq, 1H, J = 10.6, 1.2 Hz), 5.11
(dq, 1H, J = 17.6, 1.6 Hz), 5.97 (m, 1H), 6.37 (s, 2H), 6.56 (s,
2H), 7.37-7.96 (m, 5H). MS (EI), m/z 522 (M+), 417, 329,
207, 193, 176, 105, 77.
(S)-3-(3,4,5-trimethoxyphenyl)-1-O-tosyl-1,2-propanediol
[(2S)-10]
To a solution of compound (2S)-7 (0.78 g, 3.22 mmol)
in dichloromethane (20 mL) at 0 °C under N2, triethylamine
(0.49 g, 4.85 mmol) was added. After stirring the reaction
mixture for 15 min, TsCl (0.64 g, 3.36 mmol) was added. The
mixture was stirred at 0 °C for 6 h, the solvent was removed
and water (10 mL) water was added to the residue. The mix-
ture was extracted with ethyl acetate, the organic phase was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. Flash chromatography of the residue using petroleum
ether/ethyl acetate (3:1, v/v) as eluant yielded (2S)-10 (1.08
g, 85%) as a white powder. M.p. 105-106 °C. [a]2D5 -2 (c 1.2,
CHCl3). 1H NMR (200 MHz, CDCl3) d 2.45 (s, 3H), 2.72 (dd,
1H, J = 13.6, 6.8 Hz), 2.75 (dd, 1H, J = 13.8, 6.4 Hz), 3.82 (s,
(S)-3-(3,4,5-Trimethoxyphenyl)-1-O-benzoyl-2-O-(4-allyl-
2,6-dimethoxyphenyl)-1,2-propanediol [(2S)-9]
Compound (2S)-9 was prepared in an analogous man-
ner to (2R)-9, using (2R)-8 (300 mg, 0.87 mmol) and 5 (202
mg, 1.04 mmol) to give a colorless oil (226 mg, 49%). [a]D25
-4 (c 0.65, CHCl3). Other spectral data were the same as for
(2R)-9.

Asymmetry Synthesis of Two Neolignans
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 973
9H), 3.88 (m, 1H), 3.96 (dd, 1H, J = 11.8, 3.6 Hz), 4.02 (dd,
1H, J = 11.6, 3.0 Hz), 6.40 (s, 2H), 7.35 (d, 2H, J = 7.8 Hz),
7.79 (d, 2H, J = 8.2 Hz). MS (EI), m/z 396 (M+), 284, 268,
253, 224, 209, 195, 181, 167, 155, 91.
1239, 1126. 1H NMR (200 MHz, CDCl3) d 1.23 (d, 3H, J =
6.2 Hz), 2.74 (dd, 1H, J = 13.4, 7.8 Hz), 3.13 (dd, 1H, J =
13.4, 5.2 Hz), 3.34 (d, 2H, J = 6.6 Hz), 3.79 (s, 6H), 3.82 (s,
9H), 4.36 (m, 1H), 5.10 (dq, 1H, J = 10.4, 1.4 Hz), 5.13 (dq,
1H, J = 17.2, 1.8 Hz), 5.97 (m, 1H), 6.40 (s, 2H), 6.47 (s, 2H).
13C NMR (50 MHz, CDCl3) d 19.7, 40.5, 43.6, 55.9, 56.0,
60.8, 79.6, 105.5, 106.5, 115.9, 134.2, 134.8, 135.4, 136.2,
137.2, 152.8, 153.6. MS (EI), m/z 402 (M+), 362, 209, 194,
181, 168, 107, 91. HRFABMS m/z 425.1930 (C23H30O6Na re-
quires 425.1935).
(R)-3-(3,4,5-trimethoxyphenyl)-1-O-tosyl-1,2-propanediol
[(2R)-10]
Compound (2R)-10 was prepared in an analogous man-
ner to (2S)-10, using (2R)-7 (600 mg, 2.48 mmol), triethyl-
amine (375 mg, 3.71 mmol) and TsCl (496 mg, 2.60 mmol) to
give a white powder (815 mg, 83%). M.p. 107-108 °C. [a]D25
+3 (c 2.0, CHCl3). Other spectral data were the same as for
(2S)-10.
(R)-1-(3,4,5-trimethoxyphenyl)-2-O-(4-allyl-2,6-dimethoxy-
phenyl)-2-propanol [(2R)-2]
Compound (2R)-2 was prepared in an analogous man-
ner to (2S)-2, using (2S)-11 (120 mg, 0.53 mmol) and 5 (124
mg, 0.64 mmol) to give a colorless oil (117 mg, 55%). [a]D25
-2.3 (c 2.15, CHCl3). Other spectral data were the same as for
(2S)-2.
(R)-1-(3,4,5-trimethoxyphenyl)-2-propanol [(2R)-11]
To a suspension of LAH (13.8 mg, 0.36 mmol) in dry
THF (20 mL), (2S)-10 (120 mg, 0.3 mmol) was added. The
suspension was stirred for 4 h at room temperature, and
quenched with ethyl acetate and water. The mixture was ex-
tracted with ethyl acetate, the organic layer washed with
brine, dried over Na2SO4, and the solvent was removed. Flash
chromatography of the residue using petroleum ether/ethyl
acetate (4:1, v/v) as eluant yielded (2R)-11 (56 mg, 82%) as a
ACKNOWLEDGMENTS
Support from the National Natural Science Foundation
of China (No. 29972015; 20172023) is gratefully acknowl-
edged.
1
colorless oil. [a]2D5 -9 (c 1.2, CHCl3). H NMR (200 MHz,
CDCl3) d 1.26 (d, 3H, J = 6.2 Hz), 2.59 (dd, 1H, J = 13.4, 8.4
Hz), 2.75 (dd, 1H, J = 13.4, 4.4 Hz), 3.85 (s, 9H), 3.99 (m,
1H), 6.43 (s, 2H). MS (EI), m/z 226 (M+), 181, 167, 151, 107,
91, 77.
Received September 16, 2003.
(S)-1-(3,4,5-trimethoxyphenyl)-2-propanol [(2S)-11]
Compound (2S)-11 was prepared in an analogous man-
ner to (2R)-11, using (2R)-10 (150 mg, 0.38 mmol) and LAH
(17.3 mg, 0.46 mmol) to give a colorless oil (72 mg, 84%).
[a]2D5 +8 (c 1.6, CHCl3). Other spectral data were the same as
for (2R)-11.
REFERENCES
1. Jing, X.-B.; Gu, W.-X.; Ren, X.-F.; Bie, P.-Y.; Pan, X.-F.
Journal of Chinese Chemical Society 2001, 48, 59.
2. Broga, A. C. H.; Zacchino, S.; Badano, H.; Gonzalez, Sierra.
M.; Rúveda, E. A. Phytochemistry 1984, 23, 2025.
3. Isogai, A.; Murakoshi, S.; Suzuki, A. S.; Tamura. Agric.
Biol. Chem. 1973, 37, 889.
(S)-1-(3,4,5-trimethoxyphenyl)-2-O-(4-allyl-2,6-dimethoxy-
phenyl)-2-propanol [(2S)-2]
4. Oliveiria, M. M. De; Sampaio, M. R. P. Cienc. Cult. 1980,
32, 104.
To a solution of 5 (159 mg, 0.82 mmol) and DIAD (166
mg, 0.82 mmol) in dry THF at room temperature under nitro-
gen a solution of PPh3 (215 mg, 0.82 mmol) and (2R)-11 (154
mg, 0.68 mmol) in dry THF (10 mL) was added dropwise. Af-
ter stirring the mixture overnight, the solvent was removed.
Flash chromatography of the residue using petroleum
ether/ethyl acetate (9:1, v/v) as eluant yielded a colorless oil
(2S)-2 (159 mg, 57%). [a]2D5 +1.9 (c 4.7, CHCl3). IR (KBr),
u/cm-1: 3393, 2933, 2837, 1588, 1503, 1459, 1421, 1330,
5. (a) Zacchino, S. A.; Bodano, H. J. Nat. Prod. 1985, 48, 830.
(b) Zacchino, S. A.; Bodano, H. J. Nat. Prod. 1988, 51, 1261.
(c) Zacchino, S. A.; Bodano, H. J. Nat. Prod. 1991, 54, 155.
(d) Zacchino, S. A. J. Nat. Prod. 1994, 57, 446.
6. Li, K.-C.; Helm, R. F. J. Chem. Soc. Perkin Trans. 1 1996,
2425.
7. Zhang, H.-J.; Tamez, P. A.; Hoang, V. D.; Tan, G.-T.; Hung,
N.-V.; Xuan, L.-T.; Huong, L.-M.; Cuong, N.-M.; Thao,

974 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Ren et al.
D.-T.; Soejarto, D. D.; Fong, H. H. S.; Pezzuto, J. M. J. Nat.
Prod. 2001, 64, 772.
11. Conserva, L. M.; Da Silva, M. S.; Braz Filho, R. Phyto-
chemistry 1990, 29, 257.
8. Forrest, J. E.; Heacock, R. A.; Forrest, T. P. J. Chem. Soc.
Perkin I 1974, 205.
12. Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G.
A.; Hartung, J.; Jeong, K. S.; Kwong, H. L.; Morikawa, K.;
Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57,
2768.
9. Barbosa-Filho, J. M.; Da Silva, M. S.; Yoshida, M.; Gottlieb,
O. R. Phytochemistry 1989,28, 2209.
10. Da Silva, M. S.; Barbosa-Filho, J. M.; Yoshida, M.; Gottlieb,
O. R. Phytochemistry 1989, 28, 3477.
13. Mitsunobu, O. Synthesis 1981, 1.