Asymmetric total syntheses of panaxytriol and panaxydol, potent antitumor agents from Panax ginseng

Article abstract of DOI:10.1016/S0040-4020(02)00423-4

A stereoselective syntheses of panaxytriol 1 and panaxydol 2 from D-arabinose using base induced double elimination of 4,5-O-isopropylidene propargyl chloride as a key step is described.

Full text of DOI:10.1016/S0040-4020(02)00423-4

TETRAHEDRON
Pergamon
Tetrahedron 58 12002) 4955±4961
Asymmetric total syntheses of panaxytriol and panaxydol, potent
antitumor agents from Panax ginsengq
J. S. Yadavp and Arup Maiti
Natural Products Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 16 October 2001; revised 19 March 2002; accepted 11 April 2002
AbstractÐA stereoselective syntheses of panaxytriol 1 and panaxydol 2 from d-arabinose using base induced double elimination of
4,5-O-isopropylidene propargyl chloride as a key step is described. q 2002 Elsevier Science Ltd. All rights reserved.
Red ginseng is the processed root of the most important
oriental medicinal plant, Panax ginseng C. A. Meyer. It
has been used as an analeptic, stomachic and erythopoietic
agent1 in Asian countries for thousand of years and is now
available as a commercial medicinal drug in Japan.2 Red
ginseng contains several chiral polyacetylenic alcohols3
including characteristic panaxytriol 13b and panaxydol 2,3a
which showed cytotoxic and antiplatelet activity,4 respec-
tively. Although these polyacetylenic alcohols have
received great attention as a potent new class of antitumor
propargyl chloride, the methodology that was recently
developed byus.
6
Retrosynthetically, panaxytriol can be divided into two
halves, an epoxide component 4 and a diacetylenic com-
ponent 3a, which could be coupled using the Yamaguchi
method7 as shown in Scheme 1.
Firstly, the diacetylenic intermediate 3a was constructed.
Accordingly d-arabinose was transformed to 2,3:4,5-diiso-
propylidene arabinose 5 following a known procedure.8
Compound 5 was converted to dibromovinyl 6 in the
presence of PPh3, CBr4 in DCM at 08C.9a When dibromo-
vinyl compound 6 was treated with 2.5 equiv. of LDA in
THF at 2788C and quenched with 1HCHO)n at 08C10 it
produced propargyl alcohol 7 in 82% yield. This was
5
agent, onlya few syntheses have been reported.
The structures of panaxytriol and panaxydol were evidenced
as 13R,9R,10R)-heptadec-1-ene-4,6-diyne-3,9,10-triol and
13R,9R,10S)-9,10-epoxy-heptadec-1-ene-4,6-diyn-3-ol,
respectively.5 Herein we describe the syntheses of both the
natural products from the same intermediate in detail. The
salient feature of our syntheses is the utilization of ef®cient
and practical preparation of chiral diacetylenic alcohols via
base mediated double elimination of 4,5-O-isopropylidene
converted to propargyl chloride 8 byre¯uxing with PPh
3
and CCl4 in presence of sodium bicarbonate.11 The
addition of 3 equiv. of LiNH2 in liq. NH3 to this chloride
8 produced chiral diacetylenic alcohol 3 in 85% yield. The
Scheme 1.
q IICT Communication no. 4781.
Keywords: asymmetric total synthesis; Panax ginseng; panaxytriol.
Corresponding author. Tel.: 191-40-7193434; fax: 191-40-7160512; e-mail: yadav@iict.ap.nic.in
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020102)00423-4

4956
J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
Scheme 2. Reagents and conditions: 1a) See Ref. 8; 1b) PPh3, CBr4, DCM, rt, 86%; 1c) LDA, 1HCHO)n, 2788C-rt, 82%; 1d) PPh3, CCl4, re¯ux, 96%; 1e) LiNH2,
liq. NH3, 85%; 1f) TBDPSCl, imidazole, DCM, rt, 88%.
Scheme 3. Reagents and conditions: 1a) Ti1OiPr)4, PMBOH, toluene, re¯ux, 84%; 1b) TBSCl, imidazole, DCM, rt, 88%; 1c) TsCl, Et3N, DCM, rt, 80%;
1d) TBAF, THF, rt, 92%.
hydroxyl group was protected as a silyl ether using
TBDPSCl and imidazole to give retron 3a in 88% yield
1Scheme 2).
yield. Finally, diol 15 was converted to ole®n 16 with
PPh3, I2, and imidazole in re¯uxing toluene15 in 89%
yield. Selective deprotection of the PMB group with DDQ
in aq. DCM16 afforded 17. This was treated with TBAF
affording panaxytriol 1; 13R,9R,10R)-heptadec-1-ene-4,6-
diyne-3,9,10-triol in 91% yield.
In order to synthesize the epoxide 4 we have prepared
epoxyalcohol 9 according to the known procedure.12 This
was subjected to Ti1iOPr)4 mediated regioselective open-
ing13 of the epoxide to afford 1,2 diol 10 in 84% yield as
single regioisomer. After silylation and tosylation of the
hydroxyl groups in 10, treatment with TBAF effected
deprotective elimination to yield 4 in 64% overall yield
1Scheme 3).
1
Synthetic panaxytriol 1 showed a superimposable H and
13C NMR spectra with the reported data of the natural
product.5d,e Moreover the optical rotation of synthetic 1
was close to the value reported for the natural sample:
25
synthetic {[a]D ˆ222.1 1c 1.5, CHCl3)} and natural
{[a]Dˆ225.4 1c 1.54, CHCl3)}.
The stage was now set to carryout the coupling of di-
acetylenic alcohol 3a and the epoxide 4 under Yamaguchi
conditions7 to afford regioselective ring opening product 13
in 75% yield as shown in the Scheme 4. The secondary
hydroxyl group in 13 was protected as its tert-butyl-
diphenylsilyl 1TBDPS) ether to yield 14, which was
subjected to selective acetonide deprotection with
CuCl2´2H2O in acetonitrile14 to produce diol 15 in 94%
Tosylation of the alcohol 17, followed bytreatment with
TBAF readilyafford panaxydol 2. This also showed H
1
and 13C NMR spectra in agreement with the natural
25
isomer and also showed {[a]D ˆ286.3 1c 1.5, CHCl3)}
which was also close to the reported values
25
25
{[a]D ˆ281.8 1c 1.52, CHCl3)} and {[a]D ˆ296.1 1c
1.30, CHCl3)} 1Scheme 5).5b

J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
4957
Scheme 4. Reagents and conditions: 1a) BuLi, BF3´OEt2, 2788C, 75%; 1b) TBDPSCl, imidazole, CH2Cl2, rt, 91%; 1c) CuCl2´2H2O, CH3CN, rt, 94%; 1d) PPh3,
I2, imidazole, toluene, re¯ux, 89%; 1e) DDQ, CH2Cl2, rt, 82%; 1f) TBAF, THF, rt, 91%.
Scheme 5. Reagents and conditions: 1a) TsCl, Et3N, DCM, rt, 81%; 1b) TBAF, THF, rt, 76%.
In conclusion, the synthesis of the title compounds
demonstrates the practical utilityof the methodology, the
preparation of chiral diacetylenic alcohols, developed by us
and will ®nd widespread application in the synthesis of this
type of compounds.
in handling all air and moisture-sensitive reagents. Reac-
tions were monitored by analytical thin layer chromato-
graphy1TLC) using 0.25 mm E.Merk precoated silicagel
plate 160F254). The spots were detected using UV light
1254 nm), blowing I2 or bydipping into anisaldehdye/
sulfuric acid 1A) or b-napthol/sulfuric acid 1B) solution
followed bycharring on a hot plate. Product puri®cation
by¯ash column chromatographywas performed using on
silica gel 1100±200 mesh). Solutions in organic solvents
were dried over anhydrous sodium sulfate and solvents
were stripped off with a Buchi rotaryevaporator connected
to water aspirator. Trace solvent was removed on a vacuum
pump. All compounds were stored at 258C in vials ¯ushed
with nitrogen. Compound names were given according to
IUPAC nomenclature using ACD/Name software version
1.0b.
1.Experimental
1.1. General remarks
Melting points were recorded on a Buchi R-535 apparatus.
Infrared 1IR) spectra were recorded on a Perkin±Elmer-
Infrared-683 spectrophotometer with NaCl optics. Proton
magnetic resonance 11H NMR) and carbon magnetic
resonance 113C NMR) spectra were recorded on Varian
GEMINI-200, Varian UNITY-400 and Varian INOVA-
500 NMR spectrometer in deuteriochloroform unless other-
wise stated. In the 1H NMR spectra tetramethysilane 1TMS)
1d 0 ppm) was used as an internal reference, where as for
13C NMR spectra, CDCl3 1d 77.0 ppm) was used as an inter-
nal reference. Chemical shifts were reported in ppm down-
®eld from TMS and were given on the d-scale. The
multiplicity, coupling constants 1hertz), and number of
protons were indicated in parentheses and were speci®ed
as s 1singlet), d 1doublet), t 1triplet), q 1quartet), m 1multiplet
for unresolved lines), br 1broad) etc.13C spectra were
obtained with proton decoupling. Mass measurements
were carried out on either on Fnnigan-MAT1020B or
MicroMass VG70-70H mass spectrometer operating at
70 eV using direct inlet system and were given in the
mass units 1m/z). Unless otherwise stated, all nonaqueous
reactions were performed under an atmosphere of nitrogen
in ¯ame-dried glass equipped with stir bar and a rubber
septum. Standard inert atmosphere techniques were used
Pyridine and triethylamine 1Et3N) were dried over KOH.
Solvents were dried and puri®ed in the following fashion:
toluene and benzene was distilled over P2O5; Et2O and THF
were distilled from sodium-benzophenone ketyl; dichloro-
methane 1CH2Cl2) and dimethyl sulphoxide 1DMSO)
distilled from calcium hydride and methanol was distilled
from magnesium methoxide.
1.1.1.
4-'2,2-Dibromovinyl)-5-[2,2-dimethyl-'4R)-1,3-
dioxolan-4-yl]-2,2-dimethyl-'4R,5S)-1,3-dioxolane '6).
To a stirred solution of CBr4 14.30 g, 13.0 mmol) in dry
DCM 180 mL) under nitrogen, was added dropwise at
2208C a solution of PPh3 15.12 g, 19.56 mmol) in dry
DCM 150 mL). An intense yellow color developed which
darkened after 30 min at this temperature. Then a solution of
aldehyde 5 11.5 g, 6.52 mmol) and Et3N 10.90 mL,
6.5 mmol) in dryDCM 150 mL) was added at the same
temperature. The mixture was allowed to warm to 08C.

4958
J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
After stirring at 08C for 30 min, the reaction mixture was
warmed to room temperature and concentrated to 90 mL the
mixture was poured into 450 mL of hexane. The mixture
was ®ltered through a Celite pad and the solid was washed
with cold ether. The ®ltrate was concentrated under reduced
pressure, and the product was puri®ed by¯ash column chro-
matographyto yield 2.17 g of 6 in 86% yield. Rfˆ0.33 110%
amide 1prepared from 0.1 g, 14.28 mg atom of Li) in liquid
ammonia 120 mL), propargyl chloride 8 11.0 g, 3.64 mmol)
in THF/HMPA 15:1, 2 mL) was added and stirred for
30 min. The reaction was quenched with solid ammonium
chloride 11 g) and excess ammonia was evaporated. The
residue was dissolved in water and extracted with ether.
The organic layer was washed, dried, and evaporated
under reduced pressure. The crude product was puri®ed
by¯ash column chromatography1eluent: 15% ethyl acetate
in hexane) to afford diacetylenic alcohol 3 10.55 g, 85%) as
a colorless oil. Rfˆ0.48 125% EtOAc in hexane);
25
EtOAc/hexane; A: greenish blue); [a]D ˆ11.18 1c 3.77,
CHCl3); IR 1®lm) nmax 2990, 2935, 2884, 1630, 1455, 1380,
1216, 1155, 1067, 879 cm21; 1H NMR 1200 MHz, CDCl3) d
1.35, 1.41 12s, 12H, 2£C1CH3)2), 3.75 1m, 2H, CH21O)),
4.10 1m, 2H, CH1O)CH1O)), 4.52 1m, 1H, Br2CCHCH1O)),
6.45 1d, Jˆ7.5 Hz, 1H, Br2CCH); 13C NMR 150 MHz,
CDCl3) d 25.27, 26.72, 26.98 12C), 66.84, 76.06, 79.18,
80.26, 94.65, 109.65, 110.26, 135.59; Anal. Calcd for
C12H18Br2O4: C 37.33, H 4.70. Found: C 37.30, H 4.85.
25
[a]D ˆ18.3 1c 1.0, CHCl3); IR 1neat) nmax 3450, 3310,
2220 cm21; H NMR 1400 MHz, CDCl3) d 1.35, 1.42 12s,
1
6H, C1CH3)2), 2.11 1s, 1H, CuCH), 2.20 1br s, 1H, OH,
exchangeable with D2O), 4.0±4.2 1series m, 3H), 4.33 1m,
1H, CHOH); 13C NMR 150 MHz, CDCl3) d 25.73, 26.96,
63.89, 64.84, 66.09, 66.59, 69.27, 69.43, 74.54, 111.02;
Mass 1m/z) 165 1M12CH3, 30), 101 1100), 43 1100);
Anal. Calcd for C10H12O3: C 66.65, H 6.71. Found: C
66.62, H 6.79.
1.1.2. 3-[5-[2,2-Dimethyl-'4R)-1,3-dioxolan-4-yl]-2,2-di-
methyl-'4R,5S)-1,3-dioxolane-4-yl]-2-propyn-1ol '7). To
a stirred solution of 6 11.5 g, 3.89 mmol) in dryTHF
115 mL) was added a freshlyprepared solution of LDA
1prepared from 4.49 mL of 2.6 M BuLi in hexane and
1.64 mL of DIPA) at 2788C. After 2 h, the reaction mixture
was allowed to warm to 08C. To this 1HCHO)n 10.24 g,
8.0 mmol) was added and stirring was continued for
10 min at 08C and 2.5 h at room temperature. Saturated
NH4Cl solution was added to the reaction mixture and the
reaction product was extracted with ethyl acetate. The
extract was washed with water, brine, dried and concen-
trated at reduced pressure. Column chromatographed of
the crude product gave 0.81 g of propargyl alcohol 7 in
82% yield. Rfˆ0.25 110% EtOAc/hexane; A: green);
1.1.5. 1-[2,2-Dimethyl-'4R)-1,3-dioxolan-4-yl]-'1S)-2,4-
pentadiyn-1-ol '3a). TBDPSCl 10.85 mL, 3.34 mmol)
was added dropwise over 1 min to a stirred solution of
diacetylenic alcohol 3 10.5 g, 2.78 mmol) and imidazole
10.58 g, 8.5 mmol) in dryDCM 110 mL) at 0 8C under nitro-
gen. The reaction mixture was stirred at room temperature
for 24 h. The mixture was then diluted with DCM and
washed with water, brine, dried over Na2SO4, ®ltered and
concentrated giving a residue that was puri®ed bychromato-
graphy. Elution with ethyl acetate/hexane 1:9 gave
compound 3a 11.05 g, 88%) as a colorless liquid. Rfˆ0.62
25
25
[a]D ˆ124.12 1c 1.08, CHCl3); IR 1®lm) nmax 3490,
125% EtOAc/hexane); [a]D ˆ189.36 1c 2.87, CHCl3);
1
3330, 2210, 1455, 1375, 1250, 1092, 1030 cm21; H NMR
IR 1®lm) nmax 3280, 3050, 2210, 2064, 1590, 1470, 1380,
1
1200 MHz, CDCl3) d 1.31, 1.39, 1.42, 1.45 14s, 12H,
2£C1CH3)2), 3.88±4.12 1series m, 4H), 4.30 1d,
Jˆ10.0 Hz, 2H, CH2OH), 4.61 1m, 1H, CuCCH1O)); 13C
NMR 150 MHz, CDCl3) d 24.86, 25.89, 26.28, 26.64, 50.20,
66.32, 67.92, 75.67, 81.67, 82.45, 84.84, 109.67, 110.57;
Mass 1m/z) 256 1M1), 238 1M12H2O); HRMS Calcd for
C13H20O5: 256.3013. Found: 256.3010.
1260, 1111, 1074, 820, 704 cm21; H NMR 1200 MHz,
CDCl3) d 1.10 1s, 9H, SiC1CH3)3), 2.08 1s, 1H, CuCH),
3.70 1m, 2H, CH21O)), 3.82 1m, 1H, CH21O)CH1O)), 4.45
1d, Jˆ2.3 Hz, 1H, CHOTBDPS), 7.38 1m, 6H, aromatic H),
7.69 1m, 4H, aromatic H); 13C NMR 175 MHz, CDCl3)
d 19.36, 25.28, 26.41, 26.82, 26.90 12C), 64.77, 65.88,
67.43, 68.21, 70.40, 74.83, 78.49, 110.09, 127.52
12C), 127.69 12C), 129.94 12C), 132.67, 135.86, 135.91,
135.99, 136.12 12C); Mass 1m/z) 441 1M11Na); Anal.
Calcd for C26H30O3Si: C 74.60, H 7.22. Found: C 74.48,
H 7.26.
1.1.3. 4-'3-Chloro-1-propynyl)-5-[2,2-dimethyl-'4R)-1,3-
di-oxolano-4-yl]-2,2-dimethyl-'4R,5S)-1,3-dioxolane '8).
A mixture of propargyl alcohol 7 10.8 g, 3.12 mmol), tri-
phenylphosphine 11.64 g, 6.24 mmol) and sodium bicarbo-
nate 10.1 g) in carbon tetrachloride 115 mL) was heated at
re¯ux for 4 h. The solid was ®ltered, and the solvent was
evaporated and the residue was puri®ed bychromatography
to give propargyl chloride 8 0.82 g in 96% yield as a color-
less liquid. Rfˆ0.7 110% EtOAc/hexane; A: green);
1.1.6. 3-'4-Methoxybenzyloxy)-'2S,3R)-decane-1,2-diol
'10). To a stirred solution of epoxyalcohol 9 14.0 g,
23.25 mmol) and PMBOH 15.49 g, 46.5 mmol) in toluene
1100 mL), Ti1OiPr)4 110.4 mL, 34.9 mmol) was added under
nitrogen at room temperature. The reaction mixture was
then re¯uxed for 2 h. The solvent was removed under
reduced pressure and the reaction mixture diluted with
ether. Then 10% NaOH solution 125 mL) in brine was
added to this and stirred overnight. Next this was ®ltered
through a pad of Celite, washed with CHCl3, dried and
concentrated. The crude product was chromatographed to
afford 6.1 g of diol 10 in 84% yield as a colorless oil.
25
[a]D ˆ11.8 1c 1.0, CHCl3); IR 1®lm) nmax 3420, 2220,
;
1450, 1380, 1269, 1029 cm21 1H NMR 1200 MHz,
CDCl3) d 1.36, 1.39, 1.42, 1.48 14s, 12H, 2£C1CH3)2),
3.85±4.10 1series m, 4H), 4.15 1s, 2H, CH2Cl), 4.61 1m,
1H, CuCCH1O)); 13C NMR 150 MHz, CDCl3) d 24.90,
26.02, 26.27, 26.66, 34.32, 66.38, 67.92, 75.68, 80.34,
81.02, 82.55, 109.70, 110.37; Mass 1m/z) 276 1M112),
274 1M1); HRMS Calcd for C13H1935ClO4: 274.7469.
Found: 274.7482.
25
Rfˆ0.55 170% EtOAc/hexane); [a]D ˆ26.41 1c 2.64,
CHCl3); IR 1®lm) nmax 3416, 2950, 2875, 1612, 1513,
1
1462, 1377, 1248, 1176, 1038, 822, 756 cm21; H NMR
1.1.4. 1-[2,2-Dimethyl-'4R)-1,3-dioxolan-4-yl]-'1S)-2,4-
pentadiyn-1ol '3). To a stirred suspension of lithium
1200 MHz, CDCl3) d 0.87 1t, Jˆ7.0 Hz, 3H, CH3), 1.20±
1.70 1series m, 12H, 6£CH2), 2.50 and 2.89 1m, 2H, 2£OH),

J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
4959
3.45±3.78 1series m, 4H, CH21O)CH1O)CH1O)), 3.79 1s,
3H, OCH3), 4.42, 4.55 12d, Jˆ8.9 Hz, 2H, Benzylic CH2),
6.81 1d, Jˆ6.2 Hz, 2H, aromatic H), 7.20 1d, Jˆ6.2 Hz, 2H,
aromatic H); 13C NMR 150 MHz, CDCl3) d 13.97, 22.52,
25.26, 29.14, 29.63, 30.36, 31.70, 55.11, 63.30, 72.16,
72.63, 80.63, 113.73 12C), 129.40 12C), 130.25, 158.99;
Mass 1m/z): 292 1M12H2O); Anal. Calcd for C18H30O4: C
69.64, H 9.74. Found: C 69.62, H 9.80.
1.1.9. 2-[1-'4-Methoxybenzyloxy)-'1R)-octyl]-'2R)-oxirane
'4). To a solution of 12 15.0 g, 8.62 mmol) in dryTHF
150 mL) was added Bu4NF 11.0 M solution in THF,
34.5 mL, 34.5 mmol) at 08C with vigorous stirring and
was allowed to warm to room temperature. The reaction
mixture was stirred for 3 h. Saturated NH4Cl solution
110 mL) was added and resulting mixture was stirred for
few minutes. Then the mixture was diluted with water and
extracted with EtOAc. The combined organic extracts were
washed with brine, dried 1Na2SO4) and evaporated under
reduced pressure. The crude product was puri®ed by¯ash
chromatographygave epoxide 4 12.3 g, 92%) as a colorless
1.1.7. 3-'4-Methoxybenzyloxy)-1-tert-butyldimethylsilyl-
TBDMSCl
oxy-'2S,3R)-decan-2-ol
'11).
12.67 g,
17.8 mmol) was added portionwise over 5 min to a stirred
solution of diol 10 15.0 g, 16.13 mmol) and imidazole
11.65 g, 24.2 mmol) in dryDCM 150 mL) at 0 8C under
nitrogen. The reaction mixture was stirred at room tempera-
ture for 6 h. The mixture was then diluted with DCM and
washed with water. The organic layer was dried over
Na2SO4, ®ltered, and concentrated under reduced pressure.
The crude product was puri®ed bycolumn chromatography
to give mono silylated product 11 16.1 g, 88%) as a colorless
25
liquid. Rfˆ0.52 125% EtOAc/hexane); [a]D ˆ119.2 1c
2.3, CHCl3); IR 1®lm) nmax 2928, 2857, 1612, 1587, 1513,
1
1463, 1248, 1175, 1090, 1037, 919, 821, 758 cm21; H
NMR 1200 MHz, CDCl3) d 0.88 1t, Jˆ7.0 Hz, 3H, CH3),
1.35 1m, 12H, 6£CH2), 2.40 1dd, Jˆ4.8, 2.9 Hz, 1H,
Oxirane H), 2.71 1dd, Jˆ4.8, 4.2 Hz, 1H, Oxirane H),
2.90±3.01 1series m, 2H, CH1O)CH1O)), 3.79 1s, 3H,
OCH3), 4.58, 4.61 12d, Jˆ8.6 Hz, 2H, Benzylic CH2),
6.83 1d, Jˆ8.7 Hz, 2H, aromatic H), 7.25 1d, Jˆ8.7 Hz,
2H, aromatic H); 13C NMR 150 MHz, CDCl3) d 13.78,
22.25, 25.25, 28.92, 29.30, 31.55, 32.11, 42.81, 54.80,
54.92, 71.06, 79.79, 113.46 12C), 129.09 12C), 130.65,
158.90; Anal. Calcd for C18H28O3: C 73.94, H 9.65.
Found: C 73.67, H 9.98.
25
liquid. Rfˆ0.65 125% EtOAc/hexane); [a]D ˆ21.63 1c
1.7, CHCl3); IR 1®lm) nmax 3565, 2872, 1613, 1585, 1513,
1
1467, 1302, 1256, 1119, 1074, 939, 831, 777 cm21; H
NMR 1200 MHz, CDCl3) d 0.05 1s, 6H, Si1CH3)2), 0.89 1t,
Jˆ7.0 Hz, 3H, CH3), 0.90 1s, 9H, SiC1CH3)3), 1.20±1.60
1series m, 12H, 6£CH2), 2.30 1br s, 1H, CHOH exchange-
able with D2O), 3.35 1m, 1H), 3.54±3.71 1series m, 3H),
3.69 1s, 3H, OCH3), 4.47 1s, 2H, Benzylic CH2), 6.82 1d,
Jˆ6.2 Hz, 2H, aromatic H), 7.25 1d, Jˆ6.2 Hz, 2H,
aromatic H); 13C NMR 175 MHz, CDCl3) d 25.44,
25.42, 14.03, 18.20, 22.57, 25.16, 25.31, 25.61, 25.89,
29.74, 30.14, 31.61, 31.70, 55.16, 63.87, 71.91, 72.93,
79.01, 113.73 12C), 129.67 12C), 130.81, 159.18; Mass
1m/z) 409 1M12CH3); Anal. Calcd for C24H44O4Si: C
67.88, H 10.44. Found: C 67.62, H 10.31.
1.1.10. 1-[2,2-Dimethyl-'4R)-1,3-dioxolan-4yl]-8-'4-meth-
oxybenzyloxy)-1-tert-butyldiphenylsilyloxy-'1S,7R,8R)-
2,4-pentadecadiyn-7ol '13). A solution of diacetylene 3a
11.0 g, 2.39 mmol) in 10 mL THF was stirred at 2788C. A
solution of BuLi 10.95 mL, 2.4 M solution in hexane,
2.3 mmol) was added dropwise. The resulting dark brown
mixture was stirred for 30 min and then to this BF3´OEt2
10.23 mL, 2.3 mmol) was added. After another 30 min a
solution of epoxide 4 10.82 g, 2.8 mmol) in 3 mL THF
was added dropwise and stirred for 1 h at 2788C. After
that, the reaction mixture was quenched with saturated
NH4Cl solution and extracted with ethyl acetate. The extract
was washed with water, brine and dried over Na2SO4, then
concentrated under reduced pressure, puri®ed bycolumn
chromatographyto afford 1.28 g, 75% of 13 as a colorless
1.1.8. Nonyl-1-'tert-butyldimethylsilyloxymethyl)-'2R)-
'4-methoxy-benzyloxy)-'1R)-4-methyl-benzenesulfonate
'12). TsCl 12.5 g, 13.2 mmol) was added portionwise to a
stirred solution of 11 15.0 g, 11.79 mmol) and Et3N 12.5 mL,
17.97 mmol) in dryDCM at 0 8C under nitrogen. The reac-
tion mixture was stirred at room temperature for 48 h. The
mixture was then diluted with DCM and washed with water,
brine and dried over Na2SO4. Organic layer was concen-
trated, and puri®ed by¯ash column chromatographyelution
with EtOAc/hexane 1:50 to give 12 15.45 g, 80%) as a color-
25
oil. Rfˆ0.35 125% EtOAc/hexane); [a]D ˆ112.8 1c 1.07,
CHCl3); IR 1®lm) nmax 3437, 2930, 2858, 2256, 1612, 1513,
1
1463, 1427, 1374, 1249, 1073, 821, 771, 704 cm21; H
NMR 1500 MHz, CDCl3) d 0.88 1t, Jˆ7.0 Hz, 3H, CH3),
1.08 1s, 3H, CCH3), 1.09 1s, 9H, SiC1CH3)3), 1.30 1m, 10H,
5£CH2), 1.35 1s, 3H, CCH3), 1.60 1m, 2H, CH2CHOPMB),
2.27 1d, Jˆ7.1 Hz, 1H, CHOH), 2.49 1m, 2H, CuCCH2),
3.45 1dt, Jˆ6.1, 3.7 Hz, 1H, CH1OPMB)CH2), 3.69 1m, 1H,
CHH1O)CH1O)CH1OTBDPS)), 3.80 1s, 3H, OCH3), 3.90
1m, 1H, CHH1O)CH1O)CH1OTBDPS)), 4.01 1ddd,
Jˆ11.8, 8.2, 2.1 Hz, 1H, CHOH), 4.18 1m, 1H, CH1O)CH
1OTBDPS)), 4.41 1d, Jˆ2.1 Hz, 1H, CHOTBDPS), 4.50,
4.52 12d, Jˆ10.1 Hz, 2H, benzylic CH2), 6.88 1d,
Jˆ8.6 Hz, 2H, aromatic H), 7.25 1d, Jˆ8.6 Hz, 2H,
aromatic H), 7.40 1m, 6H, aromatic H), 7.71 1m, 4H,
aromatic H); 13C NMR 150 MHz, CDCl3) d 14.04, 19.31,
22.60, 24.69, 25.23, 25.29, 26.35, 26.86 13C), 29.18, 29.75,
30.31, 31.75, 55.19, 64.73, 65.80, 66.26, 70.89, 71.04,
72.34, 74.44, 77.51, 78.59, 79.67, 109.94, 113.83 12C),
127.39 12C), 127.58 12C), 129.52 12C), 129.72, 129.82,
130.20, 132.75, 135.87 12C), 135.97, 136.10 12C), 159.30;
25
less oil. Rfˆ0.65 110% EtOAc/hexane); [a]D ˆ214.62 1c
0.95, CHCl3); IR 1®lm) nmax 2929, 2857, 1612, 1513, 1463,
1367, 1300, 1251, 1177, 1096, 1036, 911, 839, 779 cm21
;
1H NMR 1200 MHz, CDCl3) d 0.05 1s, 6H, Si1CH3)2), 0.85
1s, 9H, SiC1CH3)3), 0.89 1t, Jˆ6.9 Hz, 3H, CH3), 1.15±1.40
1series m, 12H, 6£CH2), 2.42 1s, 3H, C6H4±CH3), 3.65 1m,
1H), 3.81 1s, 3H, OCH3), 3.89 1series m, 2H), 4.40, 4.50 12d,
Jˆ8.6 Hz, 2H, Benzylic CH2), 4.55 1m, 1H), 6.82 1d,
Jˆ7.2 Hz, 2H, aromatic H), 7.15 1d, Jˆ7.2 Hz, 2H,
aromatic H), 7.29 1d, Jˆ6.8 Hz, 2H, aromatic H), 7.80 1d,
Jˆ6.8 Hz, 2H, aromatic H); 13C NMR 150 MHz, CDCl3) d
25.58, 25.50, 14.02, 18.18, 21.49, 22.58, 25.48, 25.78
13C), 29.10, 29.39, 30.73, 31.75, 55.18, 61.39, 72.36,
77.31, 84.12, 113.67 12C), 127.89 12C), 129.47 12C),
129.54 12C), 130.40, 134.34, 144.34, 159.20; Anal.
Calcd for C31H50O6SSi: C 64.32, H 8.71. Found: C 64.26,
H 9.01.

4960
J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
Mass 1m/z) 734 1M11Na), 712 1M111); HRMS Calcd for
C44H59O6Si: 712.0216. Found: 712.0260.
H), 7.67 1m, 8H, aromatic H); 13C NMR 1100 MHz, CDCl3)
d 14.10, 19.31, 19.34, 22.64, 26.13, 26.94 17C), 28.57,
29.26, 29.59, 31.80, 55.20, 62.99, 65.63 13C), 71.84 12C),
72.56, 72.81, 74.41, 80.17, 113.54 12C), 127.55 12C),
127.60 12C), 127.64 13C), 127.83 13C), 129.29, 129.73,
129.80, 129.97, 130.10, 130.64, 132.33, 132.44, 133.36,
133.73, 135.80 12C), 135.94 12C), 136.02 12C), 136.13,
159.03; Mass 1m/z) 914 1M11Na2H2O).
1.1.11. 4-[8-'4-Methoxybenzyloxy)-1,7-di'tert-butyldi-
phenylsilyloxy)-'1S,7R,8R)-2,4-hexadecadiynyl]-2,2-di-
methyl-'4R)-1,3-dioxolane '14). TBDPSCl 10.48 mL,
1.9 mmol) was added portionwise over 5 min to a stirred
solution of alcohol 13 11.1 g, 1.55 mmol) and imidazole
10.68 g, 10.0 mmol) in dryDCM 15 mL) at 0 8C under nitro-
gen. The reaction mixture was stirred at room temperature
for 6 h. The mixture was then diluted with DCM and washed
with water. The organic layer was dried over Na2SO4,
®ltered, and concentrated under reduced pressure. The
crude product was puri®ed bycolumn chromatography
giving 14 11.34 g 91%) as a colorless liquid. Rfˆ0.69
1.1.13.
1-[1-Heptyl-2,8-di'tert-butyldiphenylsilyloxy)-
'1R,2R,8R)-9-decen-4,6-diynyloxymethyl]-4-methoxy-
benzene '16). The diol 15 10.9 g, 0.99 mmol), PPh3 11.0 g,
4.0 mmol) and imidazole 10.272 g, 4.0 mmol) were re¯uxed
in toluene 110 mL) with stirring. I2 10.76 g, 3.0 mmol) was
added in small portions. After 3 h, the reaction mixture was
cooled and decanted into excess aqueous sodium bicarbo-
nate and sodium thiosulfate in a separating funnel. The
residue in the ¯ask was extracted with several portions of
toluene, and the combined toluene extract was shaken with
thiosulfate until a colorless solution appeared. The organic
phase was washed with water, brine, dried over Na2SO4 and
concentrated, and the residue was puri®ed bycolumn chro-
matographyto afford ole®n 16 10.77 g, 89%) as a colorless
25
110% EtOAc/hexane); [a]D ˆ111.86 1c 2.02, CHCl3);
IR 1®lm) nmax 2925, 2860, 2250, 1613, 1376, 1219, 1107,
772 cm21; 1H NMR 1500 MHz, CDCl3) d 0.85 1t, Jˆ7.0 Hz,
3H, CH3), 1.06 1s, 3H, CCH3), 1.07 1s, 9H, Si1CH3)3), 1.09
1s, 9H, Si1CH3)3), 1.22 1m, 10H, 5£CH2), 1.35 1s, 3H,
CCH3), 1.65 1m, 2H, CH2CHOPMB), 2.43 1dd Jˆ17.2,
7.1 Hz, 1H, CuCCHH), 2.45 1dd Jˆ17.2, 7.1 Hz, 1H,
CuCCHH), 3.17 1dt, Jˆ8.8, 3.1 Hz 1H, CHOPMB), 3.77
1s, 3H, OCH3), 3.96±4.20 1series m, 6H), 4.42 1d, Jˆ5.1 Hz,
1H, CuCCHOTBDPS), 6.78 1d, Jˆ8.6 Hz, 2H, aromatic
H), 7.04 1d, Jˆ8.6 Hz, 2H, aromatic H), 7.37 1m, 12H,
aromatic H), 7.71 1m, 8H, aromatic H); 13C NMR
1100 MHz, CDCl3) d 14.09, 18.96, 22.63, 25.31, 26.12,
26.36, 26.52 14C), 26.92 12C), 26.97 12C), 28.56, 29.26,
29.59, 31.79, 55.19, 64.61 12C), 65.71, 65.91, 71.38,
71.67, 73.71, 78.72, 79.62, 80.59, 109.94, 113.59 12C),
127.44, 127.57 12C), 127.62 12C), 127.66 13C), 129.27
12C), 129.59 12C), 129.77, 130.67, 132.78, 132.94,
133.32, 133.84, 134.76 14C), 135.16, 135.89 12C), 136.12
12C), 159.01; Anal. Calcd for C60H76O6Si2: C 75.90, H 8.07.
Found: C 75.69, H 8.20.
25
liquid. Rfˆ0.76 125% EtOAc/hexane); [a]D ˆ17.84 1c
2.01, CHCl3); IR 1®lm) nmax 2926, 2855, 2256, 1613,
1592, 1512, 1465, 1426, 1302, 1247, 1108, 821, 772,
702 cm21
;
1H NMR 1500 MHz, CDCl3) d 0.89 1t,
Jˆ7.08 Hz, 3H, CH3), 1.07 1s, 9H, Si1CH3)3), 1.09 1s, 9H,
Si1CH3)3), 1.26 1m, 10H, 5£CH2), 1.65 1m, 2H,
CH2CHOPMB), 2.43 1dd, Jˆ17.2, 7.1 Hz, 1H, CuCCHH),
2.46 1dd, Jˆ17.2, 7.1 Hz, 1H, CuCCHH), 3.18 1dt, Jˆ3.1,
9.0 Hz, 1H, CH2CHOPMB), 3.77 1s, 3H, OCH3), 3.99 1m,
1H, CH2CHOTBDPS), 4.05, 4.09 12d, Jˆ10.2 Hz, 2H,
benzylic CH2), 4.83 1dt, Jˆ5.3, 1.3 Hz, 1H,
CH2vCHCHOTBDPS), 5.11 1dt, Jˆ10.1, 1.3 Hz, 1H, ole-
®nic H), 5.26 1dt, Jˆ16.9, 1.3 Hz, 1H, ole®nic H), 5.85
1ddd, Jˆ16.9, 10.1, 5.3 Hz, 1H, ole®nic H), 6.77 1d,
Jˆ8.6 Hz, 2H, aromatic H), 7.03 1d, Jˆ8.6 Hz, 2H,
aromatic H), 7.37 1m, 12H, aromatic H), 7.70 1m, 8H,
aromatic H); 13C NMR 150 MHz, CDCl3) d 14.02, 19.33,
22.61, 22.76, 26.16, 26.85, 27.01 14C), 28.68, 29.24 12C),
29.61 12C), 31.79, 55.19, 65.07 13C), 71.86 12C), 74.56,
79.81, 80.73, 113.65 12C), 115.62, 127.53 19C), 129.22
12C), 129.72 14C), 130.81, 133.05, 133.42, 133.95, 135.77
12C), 135.93 14C), 136.14 12C), 136.93, 159.08; Anal. Calcd
for C57H70O4Si2: C 78.21, H 8.07. Found: C 78.18, H 8.20.
1.1.12. 10-'4-Methoxybenzyloxy)-2,9-di'tert-butyldiphe-
nylsilyloxy)-'2R,3S,9R,10R)-4,6-heptadecadinyne-1,2-
diol '15). To a stirred solution of 14 11.1 g, 1.16 mmol) in
5 mL acetonitrile, crystals of CuCl2´2H2O 10.4 g,
2.35 mmol) was added at 08C. The solution was allowed
to warm to room temperature and stirred for 3 h. After
completion of the reaction most of the solvent was removed
at room temperature under vacuum. The crude was taken in
ether and washed with aq. NaHCO3 solution, brine and dried
over Na2SO4. Solvent was removed and puri®ed over silica
gel to give diol 15 10.99 g, 94%) as a colorless liquid.
1.1.14. 1-Heptyl-2,8-di'tert-butyldiphenylsilyloxy)-'1R,
2R,8R)-9decen-4,6-diynyl-alcohol '17). Compound 16
10.75 g, 0.86 mmol) was taken in 4 mL aq. DCM 1DCM/
H2O 19:1), DDQ 10.295 g, 1.3 mmol) was added to it and
the reaction mixture was stirred for 1 h at room temperature.
The reaction mixture was ®ltered off and the ®ltrate was
washed with 5% NaHCO3 solution, brine, and dried over
Na2SO4. Puri®ed bycolumn chromatographygave 0.53 g of
17 in 82% yield. Rfˆ0.76 125% EtOAc/hexane);
25
Rfˆ0.25 125% EtOAc/hexane); [a]D ˆ123.2 1c 2.35,
CHCl3); IR 1®lm) nmax 3480, 3072, 2930, 2858, 2255,
1612, 1589, 1513, 1466, 1428, 1375, 1249, 1109, 822,
;
704 cm21 1H NMR 1500 MHz, CDCl3) d 0.89 1t,
Jˆ7.08 Hz, 3H, CH3), 1.06 1s, 9H, Si1CH3)3), 1.10 1s, 9H,
Si1CH3)3), 1.25 1m, 10H, 5£CH2), 1.64 1m, 2H,
CH2CHOPMB), 1.83 1br s, 1H, CH2OH), 2.41 1dd,
Jˆ17.0, 7.3 Hz, 1H, CuCCHH), 2.43 1dd, Jˆ17.0,
7.3 Hz, 1H, CuCCHH), 2.43 1d, Jˆ5.4 Hz, 1H, CHOH),
3.15 1dt, Jˆ9.0, 3.3 Hz, 1H, CHOPMB), 3.66 1m, 2H,
CH2OH), 3.76 1s, 3H, OCH3), 3.83 1m, 1H, CHOH), 3.95
1dt, Jˆ7.3, 4.3 Hz, 1H, CH2CHOTBDPS), 4.0, 4.09 12d,
Jˆ8.8 Hz, 2H, benzylic CH2), 4.46 1d, Jˆ4.6 Hz, 1H,
CuCCHOTBDPS), 6.73 1d, Jˆ8.6 Hz, 2H, aromatic H),
6.98 1d, Jˆ8.6 Hz, 2H, aromatic H), 7.36 1m, 12H, aromatic
25
[a]D ˆ24.79 1c 0.90, CHCl3); IR 1®lm) nmax 3450, 2930,
1
2853, 2250, 1522, 1430, 1108 cm21; H NMR 1400 MHz,
CDCl3) d 0.89 1t, Jˆ7.08 Hz, 3H, CH3), 1.06 1s, 9H,
Si1CH3)3), 1.08 1s, 9H, Si1CH3)3), 1.25 1m, 12H, 6£CH2),
1.91 1m, 1H, OH exchangeable with D2O), 2.43 1dd,
Jˆ16.9, 7.3 Hz, 1H, CuCCHH), 2.43 1dd, Jˆ16.9,
7.3 Hz, 1H, CuCCHH), 3.60 1m, 2H, CH1O)CH1O)), 4.78

J. S. Yadav, A. Maiti / Tetrahedron 58 -2002) 4955±4961
4961
1dt, Jˆ5.5, 1.4 Hz, 1H, CvCCH1OTBDPS)), 5.10 1dt,
Jˆ10.2, 1.4 Hz, 1H, ole®nic H), 5.22 1dt, Jˆ17.2, 1.4 Hz,
1H, ole®nic H), 5.80 1ddd, Jˆ17.2, 10.2, 5.5 Hz, 1H, ole-
®nic H), 7.35 1m, 12H, aromatic H), 7.70 1m, 8H, aromatic
H); Anal. Calcd for C49H62O3Si2: C 77.94, H 8.28. Found: C
77.99, H 8.40.
CHCl3). All other data are in agreement with the earlier
report.5
Acknowledgements
One of the authors A. M. thanks CSIR, New Delhi, India for
®nancial assistance.
1.1.15. '3R,9R,10R)-1-Heptadecen-4,6-diyne-3,9,10-triol
'1). To a solution of 17 10.25 g, 0.33 mmol) in dryTHF
4 mL was added Bu4NF 11.0 M solution in dryTHF,
1.2 mL, 1.2 mmol) at 08C under nitrogen and the resulting
solution was allowed to attain room temp. The mixture was
stirred for 3 h and next quenched with 2 mL of NH4Cl
solution. Then diluted with water and extracted with ethyl
acetate. The combined organic layer was washed with brine,
dried and evaporated under reduced pressure. The crude
References
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1b) Saita, T.; Matsunaga, H.; Yamamoto, H.; Nagumo, F.;
Fujito, H.; Mori, M.; Katano, M. Biol. Pharm. Bull. 1994,
17, 789.
2. Matsunaga, H.; Katano, M.; Yamamoto, H.; Mori, M.; Takata,
K. Chem. Pharm. Bull. 1989, 37, 1279.
product was puri®ed by¯ash chromatographygave
1
184 mg, 91%) as a white glassywax. Rfˆ0.42 150%
data are in agreement with the earlier report.5
3. 1a) Poplawshi, J.; Wrobel, J. T.; Glinka, T. Phytochemistry
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chemistry 1995, 35, 1255.
25
EtOAc/hexane); [a]D ˆ220.1 1c 1.54, CHCl3). All other
1.1.16. 1-Heptyl-2,8-di'tert-butyldiphenylsilyloxy)-'1R,
2R,8R)-9-decen-4,6-diynyl-4-methyl-1-benzenesulfonate
'18). TsCl 195 mg, 0.5 mmol) was added portion wise to a
stirred solution of 17 1250 mg, 0.33 mmol), Et3N 10.2 mL,
1.5 mmol) and catalytic DMAP in dry DCM at 08C under
nitrogen. The reaction mixture was stirred at room tempera-
ture for 48 h. The mixture was then diluted with DCM and
washed with water, brine and dried over Na2SO4. Organic
layer was concentrated and puri®ed by ¯ash column chro-
matographyto give 18 240 mg, 81% as a colorless oil.
4. 1a) Katano, M.; Yamamoto, H.; Matsung, H.; Mori, M.;
Takata, K.; Nakamura, M. Gan to Kagakuyoho 1990, 17,
1045. 1b) Matsunaga, H.; Katano, M.; Saito, T.; Tamamoto,
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Fujito, H.; Mori, M.; Katano, M. Biol. Pharm. Bull. 1994,
17, 789.
25
Rfˆ0.25 110% EtOAc/hexane, B: red); [a]D ˆ11.02 1c
5. 1a) Satosh, M.; Takenchi, N.; Fujimoto, Y. Chem. Pharm.
Bull. 1997, 45, 1114. 1b) Lu, W.; Zheng, G.; Aisa, H. A.;
Cai, J. Tetrahedron Lett. 1998, 39, 9521. 1c) Lu, W.; Zheng,
G.; Cai, J. Synlett 1998, 737. 1d) Zheng, G.; Lu, W.; Aisa,
H. A.; Cai, J. Tetrahedron Lett. 1999, 40, 2181. 1e) Lu, W.;
Zheng, G.; Gao, D.; Cai, J. Tetrahedron 1999, 55, 7157.
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1999, 55, 12563.
0.85, CHCl3); IR 1®lm) nmax 2930, 2857, 2255, 1613,
1513, 1462, 1370, 1258, 1180, 1090 cm21 1H NMR
;
1200 MHz, CDCl3) d 0.89 1t, Jˆ7.0 Hz, 3H, CH3), 1.07 1s,
9H, Si1CH3)3), 1.09 1s, 9H, Si1CH3)3), 1.26 1m, 10H,
5£CH2), 1.65 1m, 2H, CH2CHOTs), 2.35 1m, 2H,
CuCCH2), 2.40 1s, 3H, aromatic CH3), 3.91±4.08 1series
m,
2H,
CH1O)CH1O)),
4.81
1m,
1H,
CH2vCHCHOTBDPS), 5.17 1dt, Jˆ9.8, 1.1 Hz, 1H, ole-
®nic H), 5.26 1dt, Jˆ16.9, 1.1 Hz, 1H, ole®nic H), 5.85
1ddd, Jˆ16.9, 9.8, 5.3 Hz, 1H, ole®nic H), 7.26±7.43 1m,
14H, aromatic H), 7.61±7.81 1m, 10H, aromatic H); Anal.
Calcd for C56H68O5SSi2: C 73.95, H 7.56. Found: C 73.59, H
7.64.
6. Yadav, J. S.; Maiti, A. Tetrahedron Lett. 2001, 42, 3909.
7. Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983, 24, 391.
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109, 5765. 1b) Li, Y.-L.; Mao, X.-H.; Wu, Y.-L. J. Chem.
Soc., Perkin Trans. 1 1995, 1559.
1.1.17. 8-[3-Heptyl-'2R,3S)-oxiran-2-yl]-'3R)-1-octen-
4,6-diyn-3-ol '2). To a solution of 18 10.24 g, 0.26 mmol)
in dryTHF 4 mL was added Bu NF 11.0 M solution in dry
4
10. 1a) McIntosh, M. C.; Weinreb, S. M. J. Org. Chem. 1983, 48,
4823. 1b) Grandjean, D.; Pale, P.; Chuche, J. Tetrahedron Lett.
1994, 35, 3529.
THF, 1.5 mL, 1.5 mmol) at 08C under nitrogen and the
resulting solution was allowed to attain room temperature.
The mixture was stirred for 3 h and next quenched with
2 mL of NH4Cl solution. Then diluted with water and
extracted with ethyl acetate. The combined organic layer
was washed with brine, dried and evaporated under reduced
pressure. The crude product was puri®ed by¯ash chromato-
graphygave 2 151 mg, 76%) as a colorless oil. Rfˆ0.25
11. Lee, J. B. J. Am. Chem. Soc. 1966, 88, 3440.
12. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769.
13. Caron, M.; Sharpless, K. B. J. Org. Chem. 1985, 50, 1557.
14. Saravanan, P.; Chandrasekhar, M.; Anand, R. V.; Singh, V. K.
Tetrahedron Lett. 1998, 39, 3091.
15. Garegg, P. J.; Samuelsson, B. Synthesis 1979, 469.
16. Oikawa, Y.; Yoshioka, T.; Yanemitsn, O. Tetrahedron Lett.
1982, 23, 885.
25
110% EtOAc/hexane, B: red); [a]D ˆ286.3 1c 1.5,