Synthesis of panax acetylenes: Chiral syntheses of acetylpanaxydol, PQ-3 and panaxydiol

Article abstract of DOI:10.1248/cpb.52.418

Acetylpanaxydol (1-Ac), PQ-3 (2) and panaxydiol (3) and their optical isomers were synthesized from L-(+)-diethyl tartrate. The absolute configurations of 1-Ac, 2 and 3 were determined to be 1-Ac (3R,9R,10S), 2 (9R,10S) and 3 (3R,10S), respectively, by comparisons of their optical rotations and the NMR data of their MTPA esters with those of natural products.

Full text of DOI:10.1248/cpb.52.418

418
Chem. Pharm. Bull. 52(4) 418—421 (2004)
Vol. 52, No. 4
Synthesis of Panax Acetylenes: Chiral Syntheses of Acetylpanaxydol,
PQ-3 and Panaxydiol
Mitsuru SATOH, ,a Mitsuo WATANABE,a Masatoshi KAWAHATA,a Kunihiko MOHRI,a Yuki YOSHIDA,a
*
b
Kimiaki ISOBE,a and Yasuo FUJIMOTO
a Showa Pharmaceutical University; 3–3165 Higashitamagawagakuen, Machida, Tokyo 194–8543, Japan: and b College of
Pharmacy, Nihon University; 7–7–1 Narashinodai, Funabashi, Chiba 274–8555, Japan.
Received November 17, 2003; accepted December 15, 2003
Acetylpanaxydol (1-Ac), PQ-3 (2) and panaxydiol (3) and their optical isomers were synthesized from L-(؉)-
diethyl tartrate. The absolute configurations of 1-Ac, 2 and 3 were determined to be 1-Ac (3R,9R,10S), 2 (9R,10S)
and 3 (3R,10S), respectively, by comparisons of their optical rotations and the NMR data of their MTPA esters
with those of natural products.
Key words panaxydol; panaxydiol; panax species; polyacetylene; absolute configuration; enzyme mediated-acetylation
In previous papers we have reported the isolation and structures and the syntheses of 1-Ac, 2 and 3 from 4a.
structural elucidation of eight C17-polyacetylenes1,2) includ-
Reaction of 4a or 4b with acrolein in the presence of 1.3
ing acetylpanaxydol (1-Ac), PQ-3 (2) and panaxydiol (3) as eq of BuLi gave a diastereomeric mixture at C-3 of (9R,10S)-
well as C14-polyacetylene, PQ-8 (4a), from Panax quinque- panaxydol (1a) or (9S,10R)-panaxydol (1b), while the reac-
folium and syntheses of 4a and its optical isomer (4b) from tion performed in the presence of 3.0 eq of BuLi afforded
L-(ϩ)-diethyl tartrate (Chart 1).3) Although synthesis4,5) and a diastereomeric mixture at C-3 of (10S)-panaxydiol (3a) or
absolute structure6) of panaxydol have already been reported, its (10R)-isomer (3b). Oxidation of 1a and 1b with manga-
the absolute configuration of natural acetylpanaxydol has not nese dioxide gave (9R,10S)-3-oxo-panaxydol (2a) and its
yet been determined. In this paper, we report the absolute (9S,10R)-isomer (2b), respectively (Chart 2). Comparison of
Chart 1
Chart 2
To whom correspondence should be addressed. e-mail: ms@ac.shoyaku.ac.jp
© 2004 Pharmaceutical Society of Japan

April 2004
419
the optical rotation value of PQ-3 ([a]D Ϫ79.2°) with those (3a؅-Ac, 3b؅-Ac) were hydrolyzed with CHIRAZYME L-2,
of 2a ([a]D Ϫ77.2°) and 2b ([a]D ϩ78.0°) indicated that the C2 (Boehringer Mannheim Corp., Indianapolis, IN, U.S.A.)
absolute stereostructure of PQ-3 should be 9R, 10S (Table 2). and phosphate buffer (pH 7.4) to give the alcohols (3a؅, b؅),
Next, we attemped the separation of the diastereomeric mix- respectively (Chart 2).8) In order to determine the absolute
tures (3a, b) using CHIRAZYME (Boehringer Mannheim configurations at C-3 by application of the modified Mosher
Corp., Indianapolis, IN, U.S.A.) catalyzed acetylation and method,9) the alcohols (3a؅, a؆ and 3b؅, b؆) were converted
hydrolysis procedures.7) Treatment of 3a and 3b with vinyl into their (R)- and (S)-a-methoxy-a-(trifluoromethyl)phenyl-
acetate in the presence of CHIRAZYME L-2, C3 acetyl (MTPA) esters, respectively. The optical purities of the
(Boehringer Mannheim Corp., Indianapolis, IN, U.S.A.) gave alcohols (3a؅, a؆ and 3b؅, b؆) were more than 99%, respec-
1
the mixtures of acetates (3a؅-Ac, 3b؅-Ac) and unreacted al- tively, which were estimated on the basis of the H-NMR
cohols (3a؆, b؆), respectively, which were separated by high spectra of their MTPA esters. The above results showed that
performance liquid chromatography (HPLC). The acetates only the alcohol (3a؅, b؅) having R-configuration were enan-
tioselectively acetylated by the action of CHIRAZYME and
Table 1.
vinyl acetate. As shown in Table 1, the signals due to H2-1
H2CϭCH – CH – (C ≡ C)2 CH2CHCH(CH2 )6 CH3
and H-2 of 3a؅-(R)- and 3b؅-(R)-MTPA esters appeared at
|
OMTPA
O
higher fields than those of 3a؅-(S)- and 3b؅-(S)-MTPA esters,
respectively, thereby suggesting the stereochemistry at C-3 of
3a؅ and 3b؅ to be R-configuration. On the other hand, the sig-
nals due to H2-1 and H-2 of 3a؆-(R)- and 3b؆-(R)-MTPA es-
ters appeared at lower fields than those of 3a؆-(S)- and 3b؆-
(S)-MTPA esters, respectively. Thus, the absolute configura-
tion at C-3 of 3a؆ and 3b؆ could both be assigned as S-con-
figurations.
Panaxydol
H-1a
H-1b
H-2
1a؅: 3R, 9R, 10S
1b؅: 3R, 9S, 10R
1a؆: 3S, 9R, 10S
1b؆: 3S, 9S, 10R
Nat. product
ϩ25
ϩ30
Ϫ25
Ϫ25
ϩ30
ϩ40
ϩ40
Ϫ40
Ϫ40
ϩ40
ϩ50
ϩ50
Ϫ50
Ϫ50
ϩ50
Furthermore, the absolute configurations at C-10 of 3a؅,
3a؆ and 3b؅, 3b؆ were also determined to be 10S for 3a؅, 3a؆
and 10R for 3b؅, 3b؆, respectively, by comparison of the
NMR data of their MTPA esters (Table 1). As shown in Ta-
bles 1 and 2, comparison of the spectral data of MTPA esters
and the optical rotation value of natural panaxydiol (3) with
those of synthetic ones indicated that the absolute configura-
tion of 3 could be concluded to be 3R, 10S. Similarly, the di-
astereomeric mixtures (1a, b) at C-3 of panaxydol were sepa-
rated into 3R-isomers (1a؅, b؅) and 3S-isomers (1a؆, b؆)
through CHIRAZYME catalyzed acetylation and hydrolysis
procedures.
H2CϭCH – CH(C ≡ C)2 CHϭCHCH(CH2 )6 CH3
|
|
OMTPA
OMTPA
Panaxydiol
H-1a
H-1b
H-2
H-8
H-9
3a؅: 3R, 10S
3b؅: 3R, 10R
3a؆: 3S, 10S
3b؆: 3S, 10R
Nat. product
ϩ30
ϩ25
Ϫ35
Ϫ30
ϩ30
ϩ40
ϩ40
Ϫ40
Ϫ40
ϩ40
ϩ50
ϩ50
Ϫ50
Ϫ50
ϩ50
ϩ68
Ϫ68
ϩ68
Ϫ68
ϩ68
ϩ35
Ϫ40
ϩ45
Ϫ35
ϩ40
Dd (ϭdSϪdR) values obtained from the MTPA esters of isomers (panaxydol,
panaxydiol). Dd values are expressed in Hz.
Table 2. Optical Rotation
Panaxydol
3R, 9R, 10S
3R, 9S, 10R
3S, 9R, 10S
3S, 9S, 10R
Nat. product
Ϫ119.2°
ϩ50.6°
Ϫ48.8°
ϩ103.0°
Ϫ112.7°
(cϭ0.65, CHCl3)
(cϭ0.63, CHCl3)
(cϭ1.06, CHCl3)
(cϭ1.28, CHCl3)
(cϭ0.47, CHCl3)
Acetylpanaxydol
3R, 9R, 10S
3R, 9S, 10R
3S, 9R, 10S
3S, 9S, 10R
Nat. product
Ϫ47.5°
ϩ108.9°
Ϫ106.1°
ϩ42.9°
Ϫ43.0°
(cϭ0.60, CHCl3)
(cϭ0.73, CHCl3)
(cϭ0.43, CHCl3)
(cϭ0.52, CHCl3)
(cϭ1.15, CHCl3)
Panaxydiol
3R, 10R
3R, 10S
3S, 10R
3S, 10S
Nat. product
Ϫ57.5°
Ϫ33.7°
ϩ30.3°
ϩ45.3°
Ϫ33.4°
(cϭ0.18, CHCl3)
(cϭ0.19, CHCl3)
(cϭ0.59, CHCl3)
(cϭ0.15, CHCl3)
(cϭ1.12, CHCl3)
PQ-3
9R, 10S
9S, 10R
Nat. product
Ϫ77.2°
ϩ78.0°
Ϫ79.2°
(cϭ0.47, CHCl3)
(cϭ0.58, CHCl3)
(cϭ0.58, CHCl3)

420
Vol. 52, No. 4
acetone and 4.5 ml of pH 7.4 phosphate buffer, and then lipase (CHI-
RAZYME L-2, C2, 50 mg) was added. The reaction mixture was stirred
overnight at room temperature. The mixture was filtered by celite, and then
extracted with AcOEt (30 ml). The organic layer was washed with brine
(30 mlϫ2), dried over MgSO4 and evaporated in vacuo to leave an oil. The
Comparison of the optical rotation value of acetylpanaxy-
dol with those of synthetic acetylpanaxydols (1a؅-Ac, 1b؅-
Ac, 1a؆-Ac, 1b؆-Ac) indicated that the absolute stereostruc-
ture of acetylpanaxydol should be 3R, 9R, 10S (Table 2).
Further studies on the synthesis of Panax acetylenes are residue was purified by HPLC (hexane : AcOEtϭ7 : 1) to give 1a؅ or 1b؅
(7.5—9.6 mg, 58.1—74.5%, retention timeϭ12.4 min) as an oil.
Acetylation of Diastereomeric Mixture (3a or b) at C-3 of Panaxydiol
now in progress.
with Lipase (CHIRAZYME L-2, C3) The reaction was carried out in a
similar manner as described in acetylation of diastereomeric mixture at C-3
of panaxydol with lipase. 3a؅-Ac or 3b؅-Ac (20.5—20.1 mg, 40.3—39.5%,
retention timeϭ10.0 min) and 3a؆ or 3b؆ (18.0—19.8 mg, 40.0—44.0%, re-
tention timeϭ20.6 min). 3a؅-Ac, 3b؅-Ac: 1H-NMR d: 0.88 (3H, t,
Jϭ7.3 Hz), 1.29 (10H, br m), 1.52 (2H, t, Jϭ7.3 Hz), 2.11 (3H, s), 4.20 (1H,
m), 5.35 (1H, d, Jϭ9.9 Hz), 5.55 (1H, d, Jϭ16.7 Hz), 5.76 (1H, d,
Jϭ15.8 Hz), 5.90 (1H, ddd, Jϭ5.7, 9.9, 16.9 Hz), 5.95 (1H, m), 6.35 (1H,
dd, Jϭ5.5, 15.8 Hz).
Experimental
The 1H- and 13C-NMR spectra were measured on a JEOL JNM-EX90 and
a JEOL JNM-a500 spectrometer in CDCl3 containing tetramethylsilane
(TMS) as an internal standard. The mass spectra were recorded on a JEOL
JMS-D 300 instrument. Waco-gel (C-300) was used for column chromatog-
raphy. The optical rotations were measured on a JASCO DIP-370 polarime-
ter. Senshu pack (PEGASIL Silica 60-5, 10fϫ250 mm) column was used
for HPLC.
Diastereomeric Mixture (1a, b) at C-3 of Panaxydol n-Buli
(1.60 mmol/ml) in hexane [400 ml (0.64 mmol)] was added dropwise to a
stirred solution of 4a or 4b (98.6 mg, 0.48 mmol) in THF (2 ml) at Ϫ78 °C.
After 30 min, acrolein (100 ml) was added and stirring was continued for 3 h
at the same temperature. The reaction mixture was quenched with saturated
NH4Cl solution (1.0 ml) and then extracted with AcOEt (20 mlϫ2). The or-
ganic layer was washed with brine (10 mlϫ2), dried over MgSO4 and con-
centrated under reduced pressure to leave an oil which was purified by
HPLC (hexane : AcOEtϭ7 : 1) to give 1a or 1b (54.0—70.2 mg, 42.3—
Hydrolysis of 3a؅-Ac or 3b؅-Ac with Lipase (CHIRAZYME L-2, C2)
The reaction was carried out in a similar manner as described in hydrolysis
of 1a؅-Ac or 3b؅-Ac with lipase.
MTPA Ester of Panaxydol Isomers Five drops (large excess) of (S)-
(ϩ)- or (R)-(Ϫ)-MTPA-Cl was added to a stirred solution of panaxydol iso-
mers (5.0 mg, 0.05 mmol) in pyridine (1.0 ml) and the stirring was continued
overnight at room temperature. The mixture was diluted with AcOEt (30 ml)
and then washed successively with 1 N-HCl (20 ml) and saturated NaHCO3
solution, dried over MgSO4, and evaporated in vacuo. The residue was puri-
fied by HPLC to give (R)-(ϩ)- or (S)-(Ϫ)-MTPA ester of panaxydol isomers.
(R)-(؉)-MTPA-ester of (3R,9R,10S)-Panaxydol The 1H-NMR spec-
trum was identical with that of (R)-(ϩ)-MTPA-ester of natural panaxydol.
1H-NMR (CDCl3) d: 0.88 (3H, t, Jϭ7.2 Hz), 1.28 (8H, br m), 1.51 (4H, m),
2.41 (1H, dd, Jϭ7.0, 17.8 Hz), 2.70 (1H, dd, Jϭ5.5, 17.8 Hz), 2.97 (1H, m),
3.15 (1H, m), 3.59 (3H, s), 5.35 (1H, d, Jϭ10.1 Hz), 5.52 (1H, d,
Jϭ16.9 Hz), 5.83 (1H, ddd, Jϭ5.7, 10.1, 16.9 Hz), 6.10 (1H, d, Jϭ5.7 Hz),
7.41 (3H, m), 7.50 (2H, m).
55.0%, retention timeϭ16.4 min) as an oil. 1a, 1b: H-NMR10) d: 0.88 (3H,
1
t, Jϭ6.8 Hz), 1.29 (8H, br m), 1.52 (4H, m), 2.39 (1H, dd, Jϭ7.2, 17.8 Hz),
2.70 (1H, dd, Jϭ5.2, 17.8 Hz), 2.97 (1H, m), 3.15 (1H, m), 4.92 (1H, m),
5.25 (1H, d, Jϭ10.1 Hz), 5.47 (1H, d, Jϭ16.9 Hz), 5.95 (1H, ddd, Jϭ5.3,
10.1, 16.9 Hz), 13C-NMR d: 14.1, 19.4, 22.6, 26.4, 27.5, 29.1, 29.4, 31.7,
54.3, 57.0, 63.4, 66.3, 70.8, 74.9, 76.6, 117.1, 136.0, CI-MS: m/z: 261
(Mϩ1)ϩ.
Oxidation of 1a or 1b with MnO2 MnO2 (100 mg) was added to the
solution of 1a or 1b (13.3 mg) in CHCl3 (2.0 ml) and the reaction mixture
was stirred for 3 h at room temperature. The reaction mixture was filtered
and evaporated in vacuo. The residue was purified by column chromatogra-
phy and HPLC (hexane : AcOEtϭ7 : 1) to give 2a or 2b (7.0—6.4 mg,
53.4—48.8%, retention timeϭ7.8 min) as an oil. 2a, 2b: 1H-NMR d: 0.89
(3H, t, Jϭ6.8 Hz), 1.29 (8H, br m), 1.53 (4H, m), 2.51 (1H, dd, Jϭ6.8,
18.0 Hz), 2.77 (1H, dd, Jϭ5.7, 18.0 Hz), 3.00 (1H, m), 3.18 (1H, m), 6.23
(1H, d, Jϭ9.9 Hz), 6.41 (1H, dd, Jϭ9.9, 17.5 Hz), 6.56 (1H, d, Jϭ17.5 Hz),
13C-NMR d: 14.1, 19.8, 22.6, 26.4, 27.5, 29.2, 29.4, 31.7, 53.9, 56.9, 60.4,
65.7, 71.0, 84.5, 134.4, 137.7, 177.6, CI-MS: m/z: 259 (Mϩ1)ϩ.
Diastereomeric Mixture (3a, b) at C-3 of Panaxydiol n-Buli
(1.60 mmol/ml) in hexane [880 ml (1.4 mmol)] was added dropwise to a
stirred solution of 4a or 4b (94.0 mg, 0.46 mmol) in THF (2 ml) at Ϫ78 °C.
After 30 min, acrolein (100 ml) was added and stirring was continued for 3 h
at the same temperature. The reaction mixture was quenched with saturated
NH4Cl solution (2.0 ml) and then extracted with AcOEt (20 mlϫ2). The or-
ganic layer was washed with brine (10 mlϫ2), dried over MgSO4 and con-
centrated under reduced pressure to leave an oil, which was purified on a
HPLC (hexane : AcOEtϭ5 : 1) to give 3a or 3b (72.3—76.0 mg, 60.2—
(S)-(؊)-MTPA-ester of (3R,9R,10S)-Panaxydol The 1H-NMR spec-
trum was identical with that of (S)-(Ϫ)-MTPA-ester of natural panaxydol.
1H-NMR (CDCl3) d: 0.88 (3H, t, Jϭ7.0 Hz), 1.26 (8H, br m), 1.53 (4H, m),
2.40 (1H, dd, Jϭ7.0, 17.6 Hz), 2.69 (1H, dd, Jϭ5.7, 17.6 Hz), 2.97 (1H, m),
3.14 (1H, m), 3.55 (3H, s), 5.40 (1H, d, Jϭ9.9 Hz), 5.60 (1H, d, Jϭ16.9 Hz),
5.93 (1H, ddd, Jϭ6.1, 9.9, 16.7 Hz), 6.08 (1H, d, Jϭ6.1 Hz), 7.42 (3H, m),
7.52 (2H, m).
(R)-(؉)-MTPA-ester of (3R,9S,10R)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ 6.8 Hz), 1.26 (8H, br m), 1.52 (4H, m), 2.42 (1H, dd, Jϭ7.0,
17.8 Hz), 2.70 (1H, dd, Jϭ5.5, 17.8 Hz), 2.97 (1H, m), 3.16 (1H, m), 3.59
(3H, s), 5.35 (1H, d, Jϭ10.1 Hz), 5.52 (1H, d, Jϭ16.9 Hz), 5.83 (1H, ddd,
Jϭ5.7, 10.1, 16.9 Hz), 6.11 (1H, d, Jϭ5.7 Hz), 7.40 (3H, m), 7.52 (2H, m).
(S)-(؊)-MTPA-ester of (3R,9S,10R)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ7.2 Hz), 1.28 (8H, br m), 1.51 (4H, m), 2.40 (1H, dd, Jϭ7.0,
17.8 Hz), 2.68 (1H, dd, Jϭ5.7, 17.8 Hz), 2.97 (1H, m), 3.15 (1H, m), 3.55
(3H, s), 5.41 (1H, d, Jϭ9.9 Hz), 5.60 (1H, d, Jϭ16.9 Hz), 5.93 (1H, ddd,
Jϭ6.1, 9.9, 16.7 Hz) 6.08 (1H, d, Jϭ6.3 Hz), 7.41 (3H, m), 7.51 (2H, m).
(R)-(؉)-MTPA-ester of (3S,9R,10S)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ7.0 Hz), 1.28 (8H, br m), 1.51 (4H, m), 2.40 (1H, dd, Jϭ7.0,
17.6 Hz), 2.69 (1H, dd, Jϭ5.5, 17.8 Hz), 2.97 (1H, m), 3.15 (1H, m), 3.55
(3H, s), 5.40 (1H, d, Jϭ9.9 Hz), 5.60 (1H, d, Jϭ16.9 Hz), 5.93 (1H, ddd,
Jϭ6.1, 9.9, 16.9 Hz), 6.08 (1H, d, Jϭ6.1 Hz), 7.41 (3H, m), 7.51 (2H, m).
(S)-(؊)-MTPA-ester of (3S,9R,10S)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ6.8 Hz), 1.28 (8H, br m), 1.52 (4H, m), 2.42 (1H, dd, Jϭ6.8,
17.8 Hz), 2.70 (1H, dd, Jϭ5.5, 17.8 Hz), 2.97 (1H, m), 3.14 (1H, m), 3.59
(3H, s), 5.35 (1H, d, Jϭ10.1 Hz), 5.52 (1H, d, Jϭ16.9 Hz), 5.83 (1H, ddd,
Jϭ5.7, 10.1, 16.9 Hz,) 6.11 (1H, d, Jϭ5.9 Hz), 7.42 (3H, m), 7.50 (2H, m).
(R)-(؉)-MTPA-ester of (3S,9S,10R)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ7.0 Hz), 1.26 (8H, br), 1.51 (4H, m), 2.40 (1H, dd, Jϭ7.0,
17.8 Hz), 2.69 (1H, dd, Jϭ5.5, 17.8 Hz), 2.97 (1H, m), 3.14 (1H, m), 3.55
(3H, s), 5.40 (1H, d, Jϭ10.1 Hz), 5.60 (1H, d, Jϭ16.9 Hz), 5.93 (1H, ddd,
Jϭ6.1, 10.1, 16.7 Hz), 6.08 (1H, d, Jϭ6.1 Hz), 7.41 (3H, m), 7.51 (2H, m).
(S)-(؊)-MTPA-ester of (3S,9S,10R)-Panaxydol 1H-NMR (CDCl3) d:
0.88 (3H, t, Jϭ6.8 Hz), 1.28 (8H, br m), 1.51 (4H, m), 2.41 (1H, dd, Jϭ6.8,
17.6 Hz), 2.69 (1H, dd, Jϭ5.7, 17.6 Hz), 2.97 (1H, m), 3.15 (1H, m), 3.59
(3H, s), 5.35 (1H, d, Jϭ10.1 Hz), 5.52 (1H, d, Jϭ16.7 Hz), 5.83 (1H, ddd,
Jϭ5.88, 10.1, 16.9 Hz), 6.11 (1H, d, Jϭ5.9 Hz), 7.41 (3H, m), 7.52 (2H, m).
The MTPA Esters of Panaxydiol Isomers The MTPA esters were pre-
pared according to the method described in the synthesis of MTPA esters of
panaxydol isomers.
1
63.3%, retention timeϭ20.6 min) as an oil. 3a, 3b: H-NMR d: 0.88 (3H, t,
Jϭ7.0 Hz), 1.29 (10H, br m), 1.52 (2H, t, Jϭ6.8 Hz), 4.19 (1H, m), 4.98
(1H, m), 5.26 (1H, d, Jϭ10.1 Hz), 5.48 (1H, d, Jϭ16.9 Hz), 5.76 (1H, d,
Jϭ15.8 Hz), 5.96 (1H, ddd, Jϭ5.3, 10.1, 16.9 Hz), 6.33 (1H, dd, Jϭ5.3,
15.8 Hz), 13C-NMR d: 14.1, 22.6, 25.2, 29.2, 29.4, 31.4, 36.9, 63.6, 70.9,
72.0, 73.5, 77.2, 80.4, 108.0, 117.2, 135.9, 149.9, CI-MS: m/z: 259 (Mϩ1)ϩ.
Acetylation of Diastereomeric Mixture (1a, b) at C-3 of Panaxydol
with Lipase (CHIRAZYME L-2, C3) Lipase (CHIRAZYME L-2, C3,
80.0 mg) and vinyl acetate (40 ml, 0.44 mmol) was added to a stirred solution
of 1a or 1b (37.5 mg, 0.35 mmol) in t-butyl methyl ether (5.0 ml) and the
mixture was stirred overnight at room temperature. The reaction mixture
was filtered with celite and evaporated in vacuo. The residue was purified by
HPLC (hexane : AcOEtϭ7 : 1) to give 1a؅-Ac or 1b؅-Ac (18.4—15.0 mg,
42.2—40.0%, retention timeϭ6.0 min) and 1a؆ or 1b؆ (15.4—16.2 mg,
41.1—43.2%, retention timeϭ12.4 min) as an oil. 1a؅-Ac, 1b؅-Ac: 1H-NMR
d: 0.88 (3H, t, Jϭ7.0 Hz), 1.29 (8H, br m), 1.53 (4H, m), 2.11 (3H, s), 2.38
(1H, dd, Jϭ7.2, 17.6 Hz), 2.70 (1H, dd, Jϭ5.2, 17.6 Hz), 2.96 (1H, m), 3.14
(1H, m), 5.34 (1H, d, Jϭ9.7 Hz), 5.54 (1H, dd, Jϭ16.4 Hz), 5.87 (1H, ddd,
Jϭ5.7, 9.7, 15.6 Hz), 5.90 (1H, m), Low-MS: m/z: 302 (M)ϩ. The H- and
1
13C-NMR spectra of acetylpanaxydol were identical with those of 1a؅-Ac.
Hydrolysis of 1a؅-Ac or 1b؅-Ac with Lipase (CHIRAZYME L-2, C2)
Compound 1a؅-Ac or 1b؅-Ac (15 mg, 0.22 mmol) was dissolved in 0.5 ml of

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Di-(R)-MTPA Ester of (3R,10R)-Panaxydiol 1H-NMR (CDCl3) d:
Di-(R)-MTPA Ester of (3S,10S)-Panaxydiol 1H-NMR (CDCl3) d: 0.88
0.87 (3H, t, Jϭ7.2 Hz), 1.26 (10H, br m), 1.64 (2H, m), 3.53 (3H, s), 3.60 (3H, t, Jϭ7.0 Hz), 1.26 (10H, br m), 1.68 (2H, m), 3.55 (6H, s), 5.42 (1H, d,
(3H, s), 5.37 (1H, d, Jϭ10.1 Hz), 5.49 (1H, m), 5.53 (1H, d, Jϭ16.4 Hz), Jϭ10.1 Hz), 5.47 (1H, m), 5.61 (1H, d, Jϭ16.9 Hz), 5.65 (1H, d, Jϭ
5.78 (1H, d, Jϭ15.1 Hz), 5.84 (1H, ddd, Jϭ5.7, 10.1, 16.7 Hz), 6.16 (1H, d, 16.0 Hz), 5.94 (1H, ddd, Jϭ6.07, 10.1, 16.5 Hz), 6.13 (1H, d, Jϭ4.23 Hz),
Jϭ5.5 Hz), 6.26 (1H, dd, Jϭ7.0, 16.0 Hz), 7.41 (6H, m), 7.50 (4H, m).
6.17 (1H, dd, Jϭ 6.6, 16.0 Hz), 7.42 (6H, m) ,7.50 (4H, m).
Di-(S)-MTPA Ester of (3R,10R)-Panaxydiol 1H-NMR (CDCl3) d: 0.87
Di-(S)-MTPA Ester of (3S,10S)-Panaxydiol 1H-NMR (CDCl3) d: 0.87
(3H, t, Jϭ7.0 Hz), 1.25 (10H, br m), 1.69 (2H, m), 3.55 (6H, s), 5.42 (1H, d, (3H, t, Jϭ7.4 Hz), 1.25 (10H, br m), 1.65 (2H, m), 3.53 (3H, s), 3.59 (3H, s),
Jϭ9.9 Hz), 5.47 (1H, m), 5.61 (1H, d, Jϭ16.9 Hz), 5.65 (1H, d, Jϭ16.0 Hz), 5.36 (1H, d, Jϭ10.1 Hz), 5.49 (1H, m), 5.53 (1H, d, Jϭ17.1 Hz), 5.78 (1H,
5.94 (1H, ddd, Jϭ6.1, 10.1, 16.4 Hz), 6.12 (1H, d, Jϭ4.2 Hz), 6.18 (1H, dd, d, Jϭ15.1 Hz), 5.84 (1H, ddd, Jϭ5.9, 10.1, 16.9 Hz), 6.15(1H, d,
Jϭ 6.6, 16.0 Hz), 7.41 (6H, m), 7.50 (4H, m).
Jϭ5.70 Hz), 6.26 (1H, dd, Jϭ7.0, 16.0 Hz), 7.40 (6H, m), 7.50 (4H, m).
Di-(R)-MTPA Ester of (3R,10S)-Panaxydiol The 1H-NMR spectrum
was identical with that of di-(R)-MTPA-ester of natural panaxydiol. 1H- References and Notes
NMR (CDCl3) d: 0.87 (3H, t, Jϭ7.2 Hz), 1.26 (10H, br m), 1.69 (2H, m),
3.55 (3H, s), 3.59 (3H, s), 5.36 (1H, d, Jϭ10.1 Hz), 5.47 (1H, m), 5.53 (1H,
d, Jϭ16.9 Hz), 5.65 (1H, d, Jϭ16.0 Hz), 5.84 (1H, ddd, Jϭ5.7, 10.1,
16.9 Hz), 6.16 (1H, d, Jϭ5.70 Hz), 6.18 (1H, dd, Jϭ6.62, 15.8 Hz), 7.41
(6H, m), 7.50 (4H, m).
1) Fujimoto Y., Satoh M., Takeuchi N., Kirisawa M., Chem. Pharm. Bull.,
39, 521—523 (1991).
2) Fujimoto Y., Wang H., Satoh M., Takeuchi N., Phytochemistry, 35,
1255—1257 (1994).
3) Satoh M., Takeuchi N., Fujimoto Y., Heterocycles, 45, 177—180
(1997).
4) Lu W., Zheng G., Aisa A., Cai J., Tetrahedron Lett., 39, 9521—9522
(1998).
5) Yadav J. S., Maiti A., Tetrahedron, 58, 4955—4961 (2002).
6) Kobayashi M., Mahmud T., Umezome T., Wang, W., Murakami N.,
Kitagawa I., Tetrahedron, 53, 15691—15700 (1997).
7) Naoshima Y., Kamezawa M., Kimura T., Okimoto F., Watanabe M.,
Tachibana H., Ohtani T., Recent Res. Devel. Org. & Bioorg. Chem., 4,
1—16 (2001).
8) CHIRAZYME catalyzed acetylation of the hydroxyl group at C-10 did
not proceed with any relation to the stereochemistry.
9) Ohtani I., Kusumi T., Kachman Y., Kakisawa H., J. Am. Chem. Soc.,
113, 4092—4096 (1991).
Di-(S)-MTPA Ester of (3R,10S)-Panaxydiol The 1H-NMR spectrum
was identical with that of di-(S)-MTPA-ester of natural panaxydiol. 1H-
NMR (CDCl3) d: 0.87 (3H, t, Jϭ7.0 Hz), 1.26 (10H, br m), 1.60 (2H, m),
3.53 (3H, s), 3.55 (3H, s), 5.42 (1H, d, Jϭ10.1 Hz), 5.49 (1H, m), 5.61 (1H,
d, Jϭ16.9 Hz), 5.78 (1H, d, Jϭ15.8 Hz), 5.94 (1H, ddd, Jϭ6.1, 9.9, 16.9 Hz),
6.13 (1H, d, Jϭ6.1 Hz), 6.25 (1H, dd, Jϭ6.99, 16.0 Hz), 7.40 (6H, m), 7.51
(4H, m)
Di-(R)-MTPA Ester of (3S,10R)-Panaxydiol 1H-NMR (CDCl3) d: 0.87
(3H, t, Jϭ7.0 Hz), 1.26 (10H, br m), 1.60 (2H, m), 3.53 (3H, s), 3.55 (3H, s),
5.43 (1H, d, Jϭ10.1 Hz), 5.49 (1H, m), 5.61 (1H, d, Jϭ16.7 Hz), 5.78 (1H,
d, Jϭ15.8 Hz), 5.94 (1H, ddd, Jϭ6.1, 10.1, 16.7 Hz), 6.13 (1H, d, Jϭ6.1 Hz),
6.25 (1H, dd, Jϭ7.2, 15.8 Hz), 7.42 (6H, m), 7.51 (4H, m).
Di-(S)-MTPA Ester of (3S,10R)-Panaxydiol 1H-NMR (CDCl3) d: 0.87
(3H, t, Jϭ6.6 Hz), 1.25 (10H, br m), 1.69 (2H, m), 3.55 (3H, s), 3.59 (3H, s), 10) The compounds having the same plane chemical structure in the text
5.36 (1H, d, Jϭ10.1 Hz), 5.47 (1H, m), 5.53 (1H, d, Jϭ16.9 Hz), 5.65 (1H,
d, Jϭ16.0 Hz), 5.84 (1H, ddd, Jϭ5.9, 10.1, 16.9 Hz), 6.15 (1H, d, Jϭ6.6 Hz),
6.18 (1H, dd, Jϭ6.62, 15.8 Hz), 7.39 (6H, m), 7.50 (4H, m).
1
showed the same H- and 13C-NMR spectra in spite of the differences
in their absolute stereostructures.