Total synthesis of panaxytriol and panaxydiol

Article abstract of DOI:10.1016/j.tetasy.2011.07.007

The enantioselective total synthesis of the diyne containing natural products panaxytriol and (3S,10R)-panaxydiol from l-tartaric acid is reported. Key steps in the synthesis include the elaboration of a γ-hydroxy amide derived from tartaric acid to the r

Full text of DOI:10.1016/j.tetasy.2011.07.007

Tetrahedron: Asymmetry 22 (2011) 1261–1265
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Total synthesis of panaxytriol and panaxydiol
⇑
Kavirayani R. Prasad , Bandita Swain
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 March 2011
Revised 5 July 2011
Accepted 12 July 2011
Available online 15 August 2011
The enantioselective total synthesis of the diyne containing natural products panaxytriol and (3S,10R)-
panaxydiol from L-tartaric acid is reported. Key steps in the synthesis include the elaboration of a c-
hydroxy amide derived from tartaric acid to the required alkyne and the formation of the desired diyne
unit by a Cadiot–Chodkiewicz coupling.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Due to the biological activity of panaxytriol and the bioactivity
‘Red Ginseng’, the steamed and dried roots of plant Panax gin-
seng native to China, Japan and Korea, is a main constituent of
many medicinal formulations. Panaxytriol 1 an important contrib-
utor of ‘Red Ginseng’ was isolated by Kitagawa et al. in 1983.1 It
shows inhibitory activity against a range of tumor cell lines includ-
ing human gastric adenocarcinoma (MK-1),2 human breast carci-
noma (breast M25-SF)3 and mouse lymphoma (P388D1).4 The
relative structure of panaxytriol was found to be heptadec-1-ene-
4,6-diyne-3,9,10-triol by Takata et al.5 and the absolute structure
was evaluated as (3R,9R,10R) by the Mosher method and circular
dichroism (CD) analysis.6 Along with panaxytriol naturally occur-
ring (3R,10S)-panaxydiol was isolated from the roots of the plant
P. ginseng by Hirakura et al.7
in general associated with diyne alcohols, a handful of syntheses of
panaxytriol 1 have been reported. Cadiot–Chodkiewicz coupling8
and epoxide opening with chiral diacetylenic alcohols9 are the
common strategies employed to install the diyne system. A recent
synthesis by Cho et al. involved a tandem metathesis and metallo-
tropic [1,3]-shift as the key step,10 while Trost et al. have utilized
diasteroselective diynylation of an aldehyde in the presence of a
ProPhenol catalyst developed by them as the pivotal step for the
synthesis of panaxytriol.11
2. Results and discussion
Our approach for synthesis of panaxytriol 1 is based on the Cad-
iot–Chodkiewicz coupling of the alkyne 3 and bromo alkyne 4 for
the synthesis of the diyne unit. The synthesis of the bromo alkyne
4 was started from the primary alcohol 5 via a Corey–Fuchs alky-
nylation protocol and terminal bromination strategy. The synthesis
of 5 was envisaged from the masked tetrol 6. The synthesis of such
OH
OH
C7H15
tetrols from
c-hydroxy amide 7 derived from tartaric acid is an
established procedure in our laboratory (Scheme 1).
OH
Accordingly, the synthetic sequence commenced with synthesis
panaxytriol 1
of the masked tetrol 6 from the c-hydroxy amide 7 using a proce-
dure described by us.12 The regioselective protection of the pri-
mary hydroxy group in 6 as the benzyl ether was accomplished
by the reaction of Bu2SnO, TBAI and benzylbromide in toluene to
furnish the benzyl ether 8 in 95% yield. Treatment of 8 with sodium
hydride, carbon disulfide and methyl iodide in THF produced the
corresponding xanthate 9 in 91% yield, which upon reaction with
Bu3SnH in the presence of a catalytic amount of AIBN in refluxing
benzene furnished 10 in 97% yield. Benzyl ether deprotection of 10
with Raney Ni under an H2 atmosphere afforded the primary alco-
hol 5 in almost quantitative yield. The IBX oxidation of alcohol 5 in
DMSO at room temperature furnished the aldehyde, which upon
OH
C7H15
HO
panaxydiol 2
⇑
Corresponding author. Fax: +91 80 23600529.
E-mail address: prasad@orgchem.iisc.ernet.in (K.R. Prasad).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.07.007

1262
K. R. Prasad, B. Swain / Tetrahedron: Asymmetry 22 (2011) 1261–1265
OH
OTBDPS
Br
O
OH
C7H15
+
C7H15
O
3
OH
1
4
O
O
O
O
C7H15
C7H15
C7H15
OH
HO
HO
Me2N
O
OH
O
O
5
7
6
Scheme 1. Retrosynthesis for panaxytriol.
treatment with CBr4, PPh3 and Zn dust in dichloromethane at 0 °C
formed the dibromo alkene 11 in 85% yield. The treatment of 11
with n-BuLi at À78 °C to 0 °C yielded alkyne 12 in 72% yield. The
NBS mediated terminal bromination of alkyne 12 using a catalytic
amount of AgNO3 in acetone afforded the bromo alkyne 4 in 89%
yield (Scheme 2).
O
O
O
O
C7H15
(n-Bu)2SnO, BnBr
TBAI, CH2Cl2, Δ
20 h, 95%
C7H15
OH
C7H15
ref. 12
HO
Me2N
BnO
OH
O
O
HO
O
O
8
7
6
O
NaH, CS2, MeI
THF, 0 °C to rt
91%
n-Bu3SnH, AIBN
benzene, Δ, 97%
C7H15
C7H15
BnO
BnO
MeS
O
O
O
10
9
S
i) IBX, DMSO, rt, 3 h
ii) CBr4, PPh3, zinc dust
CH2Cl2, 0 °C
O
O
Br
C7H15
Raney Ni, H2
rt, 6 h, 98%
C7H15
HO
Br
Br
O
O
(85% over 2 steps)
11
5
O
O
NBS, AgNO3, acetone
rt, 1 h, 89%
n-BuLi, THF, 2 h
−78 °C to 0 °C, 72%
C7H15
C7H15
O
O
4
12
Scheme 2. Synthesis of bromo alkyne 4.
OTBDPS
Br
O
CuCl, n-BuNH2, NH2OH·HCl
CH2Cl2, 0 oC to rt, 0.5 h, 75%
C7H15
+
O
3
OTBDPS
OH
O
4 M HCl, MeOH
rt, 6 h, 69%
OH
C7H15
C7H15
O
OH
13
1
Scheme 3. Synthesis of panaxytriol.

K. R. Prasad, B. Swain / Tetrahedron: Asymmetry 22 (2011) 1261–1265
1263
O
n-BuLi, THF, 2 h
−78 °C to rt, 59%
C7H15
OH
NBS, AgNO3, acetone
rt, 1 h, 85%
Br
C7H15
Br
O
14
11
OTBDPS
Br
ent-3
4 M HCl, MeOH
rt, 6 h, 64%
CuCl, n-BuNH2, NH2OH·HCl
CH2Cl2, 0 °C to rt, 0.5 h, 55%
C7H15
OH
ent-2
C7H15
OH
15
16
Scheme 4. Synthesis of (3S,10R)-panaxydiol ent-2.
The copper mediated Cadiot–Chodkiewicz cross coupling be-
tween bromo alkyne 4 and silyloxyalkyne 313 furnished diyne 13
in 75% yield. Deprotection of the acetonide as well as the TBDPS
group was carried out with 4 M HCl in methanol to furnish pan-
axytriol 1 in 69% yield; the spectroscopic and physical data are in
complete agreement with those reported in the literature
(Scheme 3).9b
3.98 (m, 1H), 3.74–3.55 (m, 4H), 2.39–2.38 (m, 1H), 1.69–1.27
(m, 18H), 0.95 (t, 3H, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) d
137.9, 128.4, 127.75, 127.72, 108.7, 80.8, 77.0, 73.4, 72.0, 69.0,
33.0, 31.7, 29.6, 29.1, 27.4, 26.9, 26.0, 22.6, 14.1; HRMS for
C21H34O4 + Na calcd 373.2355, found 373.2355.
4.2. Preparation of (S)-methyl 3-(benzyloxy)-2-((4R,5R)-5-
It was found that treatment of the dibromo alkene 11 with n-
BuLi and further warming the reaction mixture to room tempera-
ture gave enyne 14 in 59% yield with E-selectivity of the alkene.
Terminal bromination of alkyne 14 with NBS in the presence of a
catalytic amount of AgNO3 furnished the bromoalkyne 15 in 85%
yield. Copper mediated Cadiot–Chodkiewicz cross coupling be-
tween the bromo alkyne 15 and alkyne ent-3 furnished diyne 16
in 55% yield. Deprotection of the TBDPS ether with 4 M HCl in
methanol furnished (3S,10R)-panaxydiol ent-2 (enantiomer of the
natural product) in 64% yield, the spectroscopic and physical data
of which are in complete agreement with those reported in the lit-
erature (Scheme 4).14
heptyl-2,2-dimethyl-1,3-dioxolan-4-yl)propanedithioate 9
To a stirred solution of 8 (0.61 g, 1.74 mmol) in dry THF (8 mL)
was added NaH (0.14 g, 3.48 mmol) at 0 °C and stirred at room
temperature. After 1 h, CS2 (0.2 mL, 3.48 mmol) was introduced
into the reaction mixture at 0 °C and then allowed to return to
room temperature for 1 h. Next, MeI (0.2 mL, 3.48 mmol) was
added at 0 °C and stirred for another 3 h. After completion of the
reaction (indicated by TLC), it was quenched with water (5 mL)
and extracted with ether (3 Â 10 mL). The combined ether layers
were washed with brine (10 mL) and dried over Na2SO4. Evapora-
tion of the solvent in vacuo and chromatographic purification using
petroleum ether/ethyl acetate (98:2) as eluent of the crude gave
the xanthate 9 (0.69 g, 91% yield) as a yellow oil. [
a]
D = À11.5 (c
1.6, CHCl3); IR (neat) 2928, 2857, 1369, 1211, 1099, 1066 cmÀ1
;
3. Conclusion
1H NMR (400 MHz, CDCl3) d 7.37–7.26 (m, 5H), 6.08–6.03 (m,
1H), 4.56 (ABq, 2H, J = 12.1 Hz), 3.94–3.72 (m, 4H), 2.58 (s, 3H),
1.60–1.26 (m, 18H), 0.87 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz,
CDCl3) d 216.3, 137.8, 128.4, 127.7, 127.6, 108.9, 79.6, 78.5, 76.4,
73.3, 68.6, 32.7, 31.8, 29.5, 29.1, 27.5, 26.5, 26.0, 22.6, 19.1, 14.1;
HRMS for C23H36O4S2 + Na calcd 463.1953, found 463.1955.
In conclusion, we have reported the stereoselective synthesis of
panaxytriol and (3S,10R)-panaxydiol from
L-tartaric acid. Key steps
in the synthesis include the elaboration of the
c-hydroxy amide
derived from tartaric acid to the required alkyne and the formation
of the required diyne unit by a Cadiot–Chodkiewicz coupling.
4. Experimental
4.3. Preparation of (4R,5R)-4-(2-(benzyloxy)ethyl)-5-heptyl-2,2-
dimethyl-1,3-dioxolane 10
4.1. Preparation of (S)-2-(benzyloxy)-1-((4R,5R)-5-heptyl-2,2-
dimethyl-1,3-dioxolan-4-yl)ethanol 8
A stirred solution of xanthate 9 (1.12 g, 2.6 mmol) in dry ben-
zene (10 mL) was heated at reflux under an argon atmosphere.
To a stirred solution of diol 6 (0.52 g, 2 mmol) in toluene
(15 mL) was added (n-Bu)2SnO (0.5 g, 2 mmol), which was refluxed
using Dean–Stark water trap for 18 h. Next, BnBr (0.2 mL, 2 mmol)
and TBAI (tetra n-butyl ammonium iodide) (1.47 g, 4 mmol) were
added to the reaction mixture and refluxed for another 2 h, after
which it was cooled to room temperature and toluene was re-
moved under reduced pressure. The residue thus obtained was di-
luted with CH2Cl2 (10 mL), after which water (5 mL) was added to
it and extracted with CH2Cl2 (3 Â 10 mL). The combined organic
layers were washed with brine (10 mL) and dried over Na2SO4.
Evaporation of the solvent followed by column chromatography
of the resulting residue using petroleum ether/EtOAc (9:1) yielded
Next,
a solution of AIBN (43 mg, 0.26 mmol) and n-Bu3SnH
(1.4 mL, 5.2 mmol), in dry benzene (5 mL) was added drop wise.
The reaction mixture was refluxed for 4 h, after which the reaction
was complete (monitored by TLC). The reaction mixture was
cooled to room temperature and then cautiously quenched by
the addition of 1% NH3 solution (10 mL). It was then extracted with
diethyl ether (3 Â 20 mL), and the combined ether layers were
washed with brine (30 mL) and dried over Na2SO4. Evaporation
of the solvent and silica gel column chromatography of the residue
using petroleum ether/ethyl acetate (98:2) as eluent yielded 10
(0.83 g, 97% yield) as a colorless oil. [
a]
D = +27.2 (c 4.1, CHCl3); IR
(neat) 2981, 2929, 2857, 1455, 1367, 1095 cmÀ1
;
1H NMR
8 (0.66 g, 95%) as a colorless oil. [
(neat) 3477, 2986, 2858, 1455, 1378, 1370, 1216, 1099 cmÀ1
NMR (400 MHz, CDCl3) d 7.37–7.26 (m, 5H), 4.57 (s, 2H), 4.04–
a]
D = +26.1 (c 1.6, CHCl3); IR
(400 MHz, CDCl3) d 7.36–7.26 (m, 5H), 4.52 (s, 2H), 3.75 (dt, 1H,
J = 8.1, 3.6 Hz), 3.73–3.54 (m, 3H), 1.90–1.80 (m, 2H), 1.53–1.27
(m, 18H), 0.88 (t, 3H, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) d
;
1H

1264
K. R. Prasad, B. Swain / Tetrahedron: Asymmetry 22 (2011) 1261–1265
138.3, 128.3, 127.6, 127.5, 107.9, 81.0, 78.1, 73.0, 67.2, 33.2, 32.7,
31.7, 29.7, 29.1, 27.3, 27.2, 26.1, 22.6, 14.1; HRMS for
chromatography with petroleum ether/ethyl acetate (98:2) as elu-
ent afforded the alkyne 12 in 72% (69 mg) yield as a colorless oil.
C21H34O3 + Na calcd 357.2406, found 357.2405.
[a]
D = +15.3 (c 1.4, CHCl3); IR (neat) 3313, 2986, 2955, 2929,
2857, 1372, 1240, 116 5, 1069 cmÀ1 1H NMR (400 MHz, CDCl3) d
;
4.4. Preparation of 2-((4R,5R)-5-heptyl-2,2-dimethyl-1,3-
dioxolan-4-yl)ethanol 5
3.81 (dt, 1H, J = 7.7, 3.9 Hz), 3.78–3.70 (m, 1H), 2.51–2.49 (m,
2H), 2.04 (t, 1H, J = 2.8 Hz), 1.62–1.28 (m, 18H), 0.88 (t, 3H,
J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) d 108.4, 80.5, 79.9, 78.3,
70.5, 33.0, 31.8, 29.6, 29.1, 27.4, 27.0, 26.0, 22.7, 22.6, 14.0.
To a solution of 10 (0.83 g, 2.49 mmol) in ethanol (15 mL) at
room temperature was added activated Raney nickel (200 mg).
The reaction mixture was stirred for 6 h under a hydrogen atmo-
sphere (balloon) at room temperature. After the reaction was com-
plete (TLC), it was filtered through a short pad of Celite and the
Celite pad was washed with ether (15 mL). Evaporation of the sol-
vent followed by column chromatography of the resulting residue
using petroleum ether/EtOAc (94:6) yielded 5 (0.6 g, 98%) as a col-
4.7. Preparation of (4R,5R)-4-(3-bromoprop-2-ynyl)-5-heptyl-
2,2-dimethyl-1,3-dioxolane 4
To a stirred solution of alkyne 12 (83 mg, 0.35 mmol) in dry ace-
tone (2 mL) were added NBS (125 mg, 0.7 mmol) and AgNO3 (6 mg,
0.035 mmol) and stirred for 1 h at room temperature. The reaction
mixture was diluted with hexane and filtered through a pad of Cel-
ite and the Celite pad was washed with diethyl ether (10 mL). The
residue obtained after evaporation of the solvent was purified by
silica gel column chromatography with petroleum ether/ethyl ace-
tate (9:1) as eluent to afford 4 as a colorless oil in (98 mg) 89%
orless oil. [
a]
D = +35.5 (c 1.4, CHCl3); IR (neat) 3434, 2986, 2930,
2858, 1378, 1241, 1056 cmÀ1
;
1H NMR (400 MHz, CDCl3) d 3.86
(m, 2H), 3.74 (dd, 1H, J = 8.6, 3.1 Hz), 3.69–3.60 (m, 1H), 2.49 (br
s, 1H), 1.85–1.71 (m, 2H), 1.53–1.26 (m, 18H), 0.86 (t, 3H,
J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) d 108.3, 80.9, 80.2, 60.9,
34.7, 32.4, 31.7, 29.7, 29.1, 27.2, 27.1, 26.0, 22.6, 14.0; HRMS for
yield. [
a]
D = +10.1 (c 2, CHCl3); IR (neat) 2986, 2929, 2857, 1378,
C14H28O3 + Na calcd 267.1936, found 267.1929.
1370, 1164, 1068 cmÀ1
;
1H NMR (400 MHz, CDCl3) d 3.80 (dt, 1H,
J = 7.7, 4.1 Hz), 3.71 (dt, 1H, J = 10.8, 5.5 Hz), 2.52 (d, 2H,
J = 5.2 Hz), 1.64–1.20 (m, 18H), 0.87 (t, 3H, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3) d 109.3, 81.1, 78.9, 76.6, 41.2, 33.7, 32.5, 30.3,
29.9, 28.1, 27.7, 26.7, 24.5, 23.4, 14.8; HRMS for C15H25BrO2 + Na
calcd 339. 0936, found 339.1049.
4.5. Preparation of (4R,5R)-4-(3,3-dibromoallyl)-5-heptyl-2,2-
dimethyl-1,3-dioxolane 11
A solution of alcohol 5 (0.6 g, 2.48 mmol) dissolved in DMSO
(6 mL) was cooled to 0 °C and IBX (1.04 g, 3.7 mmol) was added
to it. Then reaction mixture was warmed to room temperature
and stirred for 2 h. After the reaction was complete, it was cooled
to 0 °C and then quenched by the addition of ice cold water
(5 ml). The solids were removed by filtration through a short pad
of Celite and the Celite pad was washed with diethyl ether
(15 mL). The filtrate was extracted with ether (20 mL). The com-
bined ether extracts were washed with brine (30 mL) and dried
(Na2SO4). Evaporation of the solvent gave the crude aldehyde
which was subjected to the next reaction without further
purification.
To a solution of the crude aldehyde obtained above in dry
CH2Cl2 (10 mL) were added CBr4 (2.68 g, 4.9 mmol) and Zn dust
(0.52 mg, 4.9 mmol). The reaction mixture was cooled to 0 °C and
PPh3 (2.13 g, 4.9 mmol) was added. After the addition was over,
it was stirred at 0 °C for another hour. After completion of the reac-
tion (TLC), it was diluted with hexane, filtered through a short pad
of Celite and the Celite pad was washed with diethyl ether (15 mL).
Evaporation of the solvent and purification of the crude residue
thus obtained by silica gel column chromatography using petro-
leum ether/EtOAc (98:2) gave 11 (0.68 g, 85% yield) as an oil.
4.8. Preparation of ((R)-8-((4R,5R)-5-heptyl-2,2-dimethyl-1,3-
dioxolan-4-yl)octa-1-en-4,6-diyn-3-yloxy)(tert-butyl)diphenyl-
silane 13
To a stirred solution of n-BuNH2 (0.4 mL, 4.4 mmol) and dis-
tilled water (0.9 mL) was added CuCl (5 mg, 0.04 mmol) under a
flow of N2 at 0 °C, which resulted in a deep blue solution. A few
crystals of NH2OHÁHCl were added to give a colorless solution,
which is indicative of the presence of the required Cu(I) salt. A
solution of 4 (70 mg, 0.22 mmol) in CH2Cl2 (2 mL) was added at
the same temperature resulting in a yellow suspension. Next, 3
(77 mg, 0.24 mmol) in CH2Cl2 (2 mL) was slowly added
(NH2OHÁHCl should be added whenever the color of the reaction
mixture turns blue). The reaction mixture was allowed to warm
up to room temperature. After stirring for 0.5 h, the solution was
extracted with CH2Cl2 (3 Â 10 mL), dried over Na2SO4, and concen-
trated in vacuo. The crude product was purified by column chro-
matography using petroleum ether/ethyl acetate (95:5) to yield
the desired product 13 (0.1 g, 75% yield). [
a]
D = +119.8 (c 2.8,
CHCl3); IR (neat) 2958, 2956, 2931, 2858, 1113, 1067 cmÀ1
;
1H
[
a
]
D = +23.4 (c 2.1, CHCl3); IR (neat) 2985, 2955, 2929, 2857,
NMR (300 MHz, CDCl3) d 7.74–7.64 (m, 4H), 7.43–7.34 (m, 6H),
5.84 (ddd, 1H, J = 16.8, 10.1, 5.4 Hz), 5.27 (d, 1H, J = 17.0 Hz), 5.11
(d, 1H, J = 10.1 Hz), 4.82 (d, 1H, J = 5.3 Hz), 3.81 (dt, 1H, J = 7.7,
4.2 Hz), 3.71 (dt, 1H, J = 7.9, 5.3 Hz), 2.60–2.58 (m, 2H), 1.62–1.23
(m, 18H), 1.08 (s, 9H), 0.87 (t, 3H, J = 6.9 Hz); 13C NMR (100 MHz,
CDCl3) d 137.3, 136.7, 136.5, 133.9, 133.6, 130.6, 128.3, 128.3,
116.6, 109.4, 81.1, 78.9, 77.3, 76.1, 71.1, 67.5, 65.7, 33.6, 32.5,
30.4, 29.9, 28.2, 27.8, 27.5, 26.7, 24.3, 23.4, 20.1, 14.8; HRMS for
1377, 1241, 1060 cmÀ1 1H NMR (400 MHz, CDCl3) d 6.54 (t, 1H,
;
J = 7.1 Hz), 3.70–3.62 (m, 2H), 2.42 (ddd, 1H, J = 11.2, 7.2, 4.1 Hz),
2.31 (dt, 1H, J = 13.7, 6.8 Hz), 1.60–1.28 (m, 18H), 0.88 (t, 3H,
J = 7 Hz); 13C NMR (100 MHz, CDCl3) d 134.3, 108.3, 90.6, 80.1,
78.7, 36.0, 32.7, 31.7, 29.6, 29.1, 27.3, 27.0, 26.0, 22.6, 14.0.
4.6. Preparation of (4R,5R)-4-heptyl-2,2-dimethyl-5-(prop-2-
ynyl)-1,3-dioxolane 12
C36H48O3Si + Na calcd 579.3270, found 579.3275.
To a solution of 11 (0.16 g, 0.4 mmol) in dry THF (8 mL) was
slowly added n-BuLi (0.4 mL, 1.2 mmol, 2.6 M in hexane) at
À78 °C and stirred at the same temperature for 30 min. The reac-
tion mixture was warmed to 0 °C and stirred for another 0.5 h.
Next, it was cautiously quenched with water (5 mL). The reaction
mixture was extracted with diethyl ether (3 Â 10 mL) and ether
extracts were washed with brine (10 mL), dried over Na2SO4.
Evaporation of the solvent and purification by silica gel column
4.9. Preparation of (3R,9R,10R)-heptadeca-1-en-4,6-diyne-
3,9,10-triol 1
To a solution of 13 (40 mg, 0.07 mmol) in MeOH (1 mL) was
added 4 M HCl (1 mL) and stirred at room temperature for 6 h.
After the reaction was complete (indicated by TLC), MeOH was re-
moved under reduced pressure, the residue was diluted with water
(2 mL) and extracted with ethyl acetate (3 Â 5 mL). The combined

K. R. Prasad, B. Swain / Tetrahedron: Asymmetry 22 (2011) 1261–1265
1265
organic layers were washed with brine (5 mL) and dried over
Na2SO4. Evaporation of the solvent and purification of the crude
by silica gel column chromatography gave panaxytriol 1 in 69%
16 (60 mg, 55% yield). [
a
]
D = +174.6 (c 1.6, CHCl3); IR (neat) 3369,
2955, 2929, 2857, 1113, 1059 cmÀ1 1H NMR (300 MHz, CDCl3) d
;
7.74–7.67 (m, 4H), 7.45–7.38 (m, 6H), 6.31 (dd, 1H, J = 15.8,
5.6 Hz), 5.87 (ddd, 1H, J = 16.6, 10.1, 5.4 Hz), 5.76 (d, 1H,
J = 15.9 Hz), 5.29 (d, 1H, J = 16.9 Hz), 5.13 (d, 1H, J = 10.1 Hz), 4.90
(d, 1H, J = 5.2 Hz), 4.20–4.19 (br m, 1H), 1.35–1.29 (m, 12H), 1.01
(s, 9H), 0.89 (t, 3H, J = 6.9 Hz); 13C NMR (100 MHz, CDCl3) d
149.4, 136.5, 135.9, 135.8, 133.1, 132.9, 129.8, 127.6, 127.5,
115.9, 108.3, 81.3, 76.9, 74.0, 72.1, 70.3, 65.1, 36.9, 31.7, 29.7,
29.4, 29.2, 26.8, 25.2, 22.6, 14.0; HRMS for C33H42O2Si + Na calcd
521.2852, found 521.2859.
(13 mg) yield. [
a
]
D = À17.7 (c 1.2, CHCl3); lit.9b
[
a]
D = À19.5 (c
0.83, CHCl3); IR (neat) 3330, 2926, 2854, 1466, 1266, 1120 cmÀ1
;
1H NMR (400 MHz, CDCl3) d 5.94 (ddd, 1H, J = 16.9, 10.1, 5.3 Hz),
5.47 (d, 1H, J = 17 Hz), 5.25 (d, 1H, J = 10.1 Hz), 4.92 (br d, 1H,
J = 4.3 Hz), 3.65–3.57 (m, 2H), 2.62–2.53 (m, 2H), 2.46 (br s, 1H),
2.15–2.03 (br m, 2H), 1.67–1.19 (m, 12H), 0.88 (t, 3H, J = 6.8 Hz);
13C NMR (100 MHz, CDCl3) d 136.0, 117.1, 78.1, 74.8, 73.1, 72.1,
70.9, 66.4, 63.4, 33.5, 31.8, 29.5, 29.2, 25.5, 24.9, 22.6, 14.1; HRMS
for C17H26O3 + Na calcd 301.1780, found 301.1784.
4.13. Preparation of panaxydiol ent-2
4.10. Preparation of (R,E)-dodec-3-en-1-yn-5-ol 14
To a solution of 16 (40 mg, 0.08 mmol) in MeOH (1 mL) was
added 4 M HCl (1 mL) and stirred at room temperature for 6 h.
After the reaction was complete (indicated by TLC), MeOH was re-
moved under reduced pressure, and the residue was diluted with
water (2 mL) and extracted with ethyl acetate (2 Â 5 mL). The com-
bined organic layers were washed with brine (5 mL) and dried over
Na2SO4. Evaporation of the solvent and purification of the crude by
silica gel column chromatography gave the (3S,10R)-panaxydiol
To a solution of 11 (0.3 g, 0.75 mmol) in dry THF (8 mL) was
added n-BuLi (1.1 mL, 3 mmol, 2.6 M in hexane) slowly at À78 °C
and stirred at the same temperature for 30 min. The reaction mix-
ture was warmed to room temperature and stirred for another 1 h.
Next, it was cooled to 0 °C, and then cautiously quenched with
water (5 mL). The reaction mixture was extracted with diethyl
ether (3 Â 10 mL) and the ether extracts were washed with brine
(10 mL), and dried over Na2SO4. Evaporation of the solvent and
purification by silica gel column chromatography with petroleum
ether/ethyl acetate (9:1) as eluent afforded alkyne 14 (80 mg,
ent-2 in 64% (12 mg) yield.
D = +30.3 (c 0.59, CHCl3); IR (neat) 3366, 2954, 2926, 2855,
1718, 1019 cmÀ1 1H NMR (400 MHz, CDCl3) d 6.33 (dd, 1H,
[a]
D = +25.4 (c 0.6, CHCl3) lit.14
[a]
;
59% yield) as a colorless oil. [
a]
D = À14.7 (c 2.1, CHCl3); IR (neat)
J = 15.9, 5.6 Hz), 5.95 (ddd, 1H, J = 16.7, 10.1, 5.3 Hz), 5.76 (d, 1H,
J = 15.9 Hz), 5.48 (d, 1H, J = 17.0 Hz), 5.26 (d, 1H, J = 10.1 Hz), 4.98
(d, 1H, J = 4.9 Hz), 4.19 (q, 1H, J = 6.0 Hz), 2.06–2.03 (br m, 2H),
1.67–1.07 (m, 12H), 0.88 (t, 3H, J = 6.9 Hz); 13C NMR (100 MHz,
CDCl3) d 149.9, 135.9, 117.2, 108.0, 80.3, 77.5, 73.4, 72.0, 70.8,
63.6, 36.9, 31.7, 29.3, 29.1, 25.2, 22.6, 14.0. HRMS for C17H24O2 + Na
calcd 283.1674, found 283.1674.
3313, 2956, 2928, 2857, 1465, 1020 cmÀ1
;
1H NMR (400 MHz,
CDCl3) d 6.24 (dd, 1H, J = 15.9, 5.9 Hz), 5.69 (dd, 1H, J = 15.9,
1.3 Hz), 4.16–4.15 (brm, 1H), 2.88 (d, 1H, J = 1.9 Hz), 1.64–1.27
(m, 13H), 0.87 (t, 3H, J = 6.9 Hz); 13C NMR (100 MHz, CDCl3) d
147.6, 108.5, 81.6, 77.7, 72.0, 36.8, 31.7, 29.4, 29.1, 25.2, 22.6, 14.0.
4.11. Preparation of (R,E)-1-bromododec-3-en-1-yn-5-ol 15
Acknowledgments
To a stirred solution of alkyne 14 (78 mg, 0.43 mmol) in dry ace-
tone (2 mL) were added NBS (125 mg, 0.7 mmol) and AgNO3 (6 mg,
0.035 mmol) and stirred for 1 h at room temperature. The reaction
mixture was diluted with hexane, filtered through a pad of Celite
and the Celite pad was washed with diethyl ether (10 mL). Residue
obtained after evaporation of the solvent was purified by silica gel
column chromatography with petroleum ether/ethyl acetate (9:1)
as eluent to afford 15 as colorless oil (95 mg, 85% yield).
We thank Ms. Kavya Bhat for her help in the synthesis of some
of the compounds. K.R.P. is a swarnajayanthi fellow of the Depart-
ment of Science and Technology (DST), New Delhi and thanks DST
for funding. B.S thanks Council of Scientific and Industrial Research
(CSIR) for a research fellowship.
[
a]
D = +10.5 (c 0.8, CHCl3); IR (neat) 3338, 2927, 2856, 2361,
References
2342, 1698, 1527 cmÀ1 1H NMR (400 MHz, CDCl3) d 6.20 (dd,
;
1. Kitagawa, I.; Yoshikawa, M.; Yoshihara, M.; Hayashi, T.; Taniyama, T. Yakugaku
Zasshi. 1983, 103, 612.
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1H, J = 15.9, 5.9 Hz), 5.68 (dd, 1H, J = 15.9, 1.1 Hz), 4.15 (dt, 1H,
J = 12.1, 6.0 Hz), 1.67–1.27 (m, 12H), 0.88 (t, 3H, J = 7.0 Hz); 13C
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29.4, 29.1, 25.2, 22.6, 14.0.
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To a stirred solution of n-BuNH2(0.4 mL, 4 mmol) and distilled
water (0.9 mL) was added CuCl (4 mg, 0.04 mmol) under a flow
of N2 at 0 °C, which resulted in a deep blue solution. A few crystals
of NH2OHÁHCl were added to give a colorless solution, which is
indicative of the presence of the required Cu(I) salt. A solution of
15 (64 mg, 0.2 mmol) in CH2Cl2 (2 mL) was added at the same tem-
perature resulting in
a yellow suspension. Then 3 (57 mg,
0.22 mmol) in CH2Cl2 (2 mL) was slowly added (NH2OHÁHCl should
be added whenever the color of the reaction mixture turns blue).
The reaction mixture was allowed to warm up to room tempera-
ture. After stirring for 0.5 h, the solution was extracted with CH2Cl2
(3 Â 10 mL), dried over Na2SO4, and concentrated in vacuo. The
crude product was purified by column chromatography using
petroleum ether/ethyl acetate (9:1) to yield the desired product