A new chiral synthesis of bullfrog bile sterol 5β-ranol

Article abstract of DOI:10.1039/a607850h

(24R)-27-Nor-5β-cholestane-3α,7α,12α,24,26-pentol (5β-ranol) has been synthesised by the Wittig olefinic coupling of a steroidal module and a side-chain module followed by reduction and deprotection. The steroidal module is derived from cholic acid by a one-carbon degradation of the side chain to produce norcholic acid followed by the loss of a second carbon in an iododecarboxylation and then synthesis of the triphenylphosphonium iodide. The side-chain module is derived from (S)-(-)-butane-1,2,4-triol by benzylidene protection of the 2,4-diol followed by Swern oxidation to the aldehyde. This general synthetic scheme could be used to produce a range of bile sterols with the (24R)-hydroxy moiety which may have significant hepatoprotective activity against liver damage induced by free radicals or reactive metabolites.

Full text of DOI:10.1039/a607850h

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A new chiral synthesis of bullfrog bile sterol 5â-ranol
Don W. Harney and Theodore A. Macrides
Biochemistry Unit, Department of Medical Laboratory Science, RMIT University,
GPO Box 2476V, Melbourne, Vic. 3001, Australia
(24R)-27-N or-5â-cholestane-3á,7á,12á,24,26-pentol (5â-ranol) has been synthesised by the Wittig olefinic
coupling of a steroidal module and a side-chain module followed by reduction and deprotection. The
steroidal module is derived from cholic acid by a one-carbon degradation of the side chain to produce
norcholic acid followed by the loss of a second carbon in an iododecarboxylation and then synthesis of
the triphenylphosphonium iodide. The side-chain module is derived from (S)-(Ϫ)-butane-1,2,4-triol by
benzylidene protection of the 2,4-diol followed by Swern oxidation to the aldehyde. This general synthetic
scheme could be used to produce a range of bile sterols with the (24R)-hydroxy moiety which may have
significant hepatoprotective activity against liver damage induced by free radicals or reactive metabolites.
Introduction
A bile alcohol, 5β-ranol is the major bile constituent of the
bullfrog Rana catesbeina and has been shown to be (24R)-27-
nor-5β-cholestane-3α,7α,12α,24,26-pentol.1 Another bile alco-
hol, 5β-scymnol (Fig. 1), isolated from shark bile and contain-
ing the chiral 24R alcohol substituent has been identified as
(24R)-5β-cholestane-3α,7α,12α,24,26,27-hexol.2
5β-Scymnol
has been recognised as having a role in the treatment of liver
dysfunction and skin complaints,3 and is used in the treat-
ment of acne where it is known to reduce oil production in
sebaceous skin glands.4 In vivo testing has shown 5β-scymnol is
hepatoprotective against acetaminophen,5 carbon tetrachloride
and the mushroom toxin α-amanitin.6 In vitro, 5β-scymnol has
potent hydroxyl quenching activity where it is able to markedly
inhibit deoxyribose degradation in a ferrous-ascorbate Fenton
reaction system.5 Because of our interest in the (24R)-hydroxy
sterols derived from bile, we decided to develop a general
method for the synthesis of this class of sterol and for 5β-ranol
14 in particular.
Scheme 1 shows the retrosynthetic strategy envisaged for the
preparation of the required sterol. A side-chain degradation of
the C23 and C24 from cholic acid would incorporate the required
steroidal ring component. The side-chain module for 5β-ranol
14 incorporating the correct chirality for the alcohol substituent
at the C24 position utilises (S)-(Ϫ)-butane-1,2,4-triol as starting
material.
Results and discussion
In Scheme 2 the conversion of cholic acid 1 into triformylcholic
acid 2 (85%) is shown. Treatment of 2 with sodium nitrite
in trifluoroacetic acid (TFA) and trifluoroacetic anhydride
(TFAA) gave the nitrile, which after alkaline hydrolysis pro-
Scheme 1 General scheme for the preparation of 5β-ranol
OH
vided norcholic acid 3 (78%).7 Treatment of 3 with formic acid
in acetic anhydride and perchloric acid provided triformylnor-
cholic acid 4.8 3α,7α,12α-Triformyloxy-22-iodo-23,24-bisnor-
5β-cholane 5 was prepared from 4 by iododecarboxylation,
using a procedure which had previously been successfully
employed in the synthesis of 3α,7α,12α-triformyloxy-23-iodo-
24-nor-5β-cholane.9 The triformate 5 was converted into
CH2OH
OH
CH2OH
HO
OH
H
3α,7α,12α-trihydroxy-22-iodo-23,24-bisnor-5β-cholane
6 by
base-catalysed alcoholysis with methanol and the labile tri-
formyl derivative was easily removed without substantial
Fig. 1 5β-Scymnol from shark bile [(24R)-5β-cholestane-3α,7α,12α,
24,26,27-hexol]
J. Chem. Soc., Perkin Trans. 1, 1997
1353

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Table 1 5β-ranol 14 side-chain 13C NMR chemical shifts compared
with reported values1
Carbon no.
24S
24R
Synthetic ranol 14
20
21
22
23
24
25
26
36.2
18.1
32.5
35.3
70.5
40.7
60.4
36.2
18.0
32.4
35.2
70.1
40.7
60.4
36.3
18.0
32.5
35.2
70.1
40.7
60.4
Scheme 2 Reagents and conditions: i, HCO2H, Ac2O, HClO4 (85%); ii,
NaNO2, TFA, TFAA, KOH (78%); iii, HCO2H, Ac2O, HClO4 (88%); iv,
Pb(OAc)4, I2, CCl4 reflux; (91%); v, NaOMe, MeOH (80%); vi, Ph3P
(5 mol), MeCN, 44 h reflux (68%)
decomposition of the iodide. Preparation of 3α,7α,12α-
trihydroxy-23,24-bisnor-5β-cholan-22-yl(triphenyl)phosphon-
ium iodide 7 was carried out by reaction of triphenylphosphine
(5 mol equiv.) in acetonitrile under prolonged reflux.10
Attempts to prepare 3α,7α,12α-trihydroxy-22-iodo-23,24-
bisnor-5β-cholane 6 from the triacetate resulted in solvolysis of
the iodide during deacetylation. Attempts at reductive deacetyl-
ation with a mixture of aluminium chloride and lithium
aluminium hydride11 were also unsuccessful.
Scheme 3 shows the synthesis of the side-chain module and
Scheme 4 Reagents and conditions: i, PhLi–diethyl ether, 0 ЊC, 10 min,
room temp., 1 h; ii, 10 in diethyl ether added, 20 h room temp. (19%); iii,
PtO2, MeOH, 24 h room temp. (96%); iv, TSA cat., MeOH, 24 h, room
temp. (71%)
Scheme 3 Reagents and conditions: i, PhCHO, cyclohexane, TSA cat.
(72%); ii, Ϫ50 ЊC, CH2Cl2, oxalyl chloride, DMSO, Et3N (50%)
begins with the conversion of (S)-(Ϫ)-butane-1,2,4-triol 8 into
(2S-cis)-2-phenyl-1,3-dioxane-4-methanol 9 by the general
method for chiral aldehydes.12 Oxidation of alcohol 9 by
the Swern procedure13 gave (2S-cis)-2-phenyl-1,3-dioxane-4-
carbaldehyde 10 which oligomerises when stored.14 In refluxing
methanol the oligomer was both depolymerised and solubilised
prior to its use in the synthesis.
Scheme 4 shows the coupling of the steroidal and side-chain
modules by a Wittig reaction using freshly prepared phenyl-
lithium in diethyl ether to give a mixture of cis-12a and
trans-12b (19%). The olefin mixture of 12a and 12b was reduced
in the presence of a platinum catalyst to give (24R)-24,26-O-
benzylidene-3α,7α,12α,24,26-pentahydroxy-27-nor-5β-cholest-
ane 13 (96%). The reduction of the olefin required a second
charge of catalyst to initiate reduction and we ascribe this
to the presence of sulfur impurities from the Swern oxid-
ation which had poisoned the catalyst. Deprotection of the
benzylidene protected diol moiety yielded 5β-ranol 14 (71%).
Pure product was recovered only after chromatographic
removal of toluene-4-sulfonic acid catalyst which had an RF
value similar to 5β-ranol 14.
The 13C NMR data for the synthetic ranol product 14 was
compared with the literature values1 and is summarised in
Table 1.
The C24 chemical shift differentiates the two isomers. 13C
NMR indicated that the 5β-ranol prepared was the 24R isomer
and from the signal to noise ratio in the region of the (24S)
isomer at 70.5, it was calculated that the 24S isomer was present
in <5% by weight.
Experimental
1H NMR spectra were recorded on a Varian Gemini-200 (200
MHz) instrument using deuteriochloroform (or other indicated
solvents) as reference or an internal deuterium lock. The
1354
J. Chem. Soc., Perkin Trans. 1, 1997

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multiplicity of the signal is indicated as s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, br = broad, dd = doublet
of doublets, dt = doublet of triplets, etc. and J values are
expressed in Hz. 13C NMR spectra were recorded on a Varian
Gemini-200 (50.28 MHz) instrument using an internal deuter-
ium lock and proton decoupling. The chemical shift data is
given in units of δ relative to tetramethylsilane (TMS), where
δ (TMS) = 0. When required, COSY, APT, DEPT and spin
decoupling were used to assist in NMR peak assignments. High
resolution fast atom bombardment (FAB) mass measurements
were performed on a JOEL JMS-DX 300 instrument by Mr
Stuart Thomson of the Victorian College of Pharmacy,
Monash University, Melbourne, Australia using a matrix of 3-
nitrobenzyl alcohol. Novel steroidal compounds were charac-
terised by mass spectral analysis. Microanalysis was not used
for characterisation since our experience shows that steroids
often retain significant traces of solvent, despite long periods of
vacuum stripping. Analytical TLC was carried out on pre-
coated 0.25 mm thick Merck Kieselgel 60 F254 silica plates.
Visualisation was by absorption of UV light and/or by spraying
with 5% phosphomolybdic acid and 7.5% sulfuric acid in acetic
acid followed by thermal development. Flash chromatography
was carried out using Merck Kieselgel 60 (230–400 mesh). Mps
are uncorrected. Reagents were purified and dried by standard
techniques.15 THF and diethyl ether were dried from sodium
using benzophenone ketyl as indicator. Ether refers to diethyl
ether. Light petroleum refers to the fraction boiling in the range
60–80 ЊC. All reactions were performed under an atmosphere
of dry nitrogen unless indicated to the contrary. All reagents
were analytical grade and were purchased from regular com-
mercial sources.
[Found (FAB) (Mϩ Ϫ 3HCOOH), 423.155 29. C22H32I requires
423.154 88].
3á,7á,12á-Trihydroxy-22-iodo-23,24-bisnor-5â-cholane 6
To a solution of sodium (56 mg, 2.4 mmol) in dry methanol
(48 cm3) stirred under N2 was added triformyl iodide 5 (1.10 g,
1.96 mmol) in one portion. The stirred mixture was allowed to
react at room temperature for 24 h, after which time saturated
aqueous ammonium chloride (25 cm3) was added to it and
methanol was removed by rotary evaporation at 30 ЊC (caution,
this procedure causes excessive foaming). The reaction mixture
was extracted with dichloromethane (3 × 50 cm3) and the com-
bined extracts were washed with 20% aqueous sodium chloride
(8 cm3), dried (Na2SO4) and evaporated to yield the crude
product. Purification by column chromatography using a step-
wise elution of 1, 2, 3 and 5% methanol in dichloromethane
gave fractions which were monitored by TLC. Title compound 6
was isolated as a white crystalline solid (744 mg, 80%); mp
softens 108 ЊC and melts 116.5 ЊC; RF 0.47 (MeOH–CH2Cl2,
10:90); δH (200 MHz; CDCl3) 0.69 (3 H, s, 18-H), 0.85 (3 H, s,
19-H), 1.10 (3 H, d, J 6.0, 21-H), 3.13 (1 H, dd J 9.6 and 5.7, 22-
CH2), 3.33 (1 H, dd, J 9.6 and 2.4, 22-CH2), 3.43 (1 H, br m, w/2
13, 3-βH), 3.84 (1 H, m, w/2 8, 7-βH) and 3.95 (1 H, m, w/2 8,
12-βH) [Found (FAB) (Mϩ Ϫ 3H2O), 423.155 67. C22H32I
requires 423.154 88].
3á,7á,12á-Trihydroxy-23,24-bisnor-5â-cholan-22-yl(triphenyl)-
phosphonium iodide 7
To a solution of the iodo compound 6 (3.00 g, 6.29 mmol) in
anhydrous acetonitrile (65 cm3) was added triphenylphosphine
(8.25 g, 31.5 mmol) and the resulting mixture was refluxed
under N2 for 44 h; it was then evaporated to give a pale yellow
solid. The crude reaction product was broken up, washed with
dry ether (3 × 25 cm3) and filtered. Purification of the crude
product by flash chromatography using a stepwise elution of 1,
2.5, 5, 10 and 15% methanol in dichloromethane gave fractions
which were monitored by TLC. Title compound 7 was isolated
as a pale yellow crystalline solid (3.15 g, 68%); mp 176–178 ЊC;
RF 0.40 (MeOH–CH2Cl2, 12.5:87.5); δH (200 MHz; CDCl3)
0.49 (3 H, s, 18-H), 0.80 (3 H, s, 19-H), 1.08 (3 H, d, J 6.6,
21-H), 2.3–2.5 (1 H, m, 20-CH), 2.9–3.2 (1 H, t, 22-CHa), 3.32
(1 H, br m, w/2 22, 3-βH), 3.76 (1 H, m, w/2 11, 7-βH), 3.79 (1
H, m, w/2 10, 12-βH), 3.95–4.12 (1 H, m, 22-CHb) and 7.6–7.9
(15 H, m, ArH) [Found (FAB) (Mϩ Ϫ I), 611.367 53. C40H52-
O3P requires 611.365 42].
3á,7á,12á-Triformyloxy-24–nor-5â-cholan-5â-oic acid 4
Norcholic acid 3 (5.75 g, 14.6 mmol) was dissolved in 88%
formic acid (26 cm3) and 70% perchloric acid (0.25 cm3) and
heated at 50–60 ЊC for 1.5 h. The mixture was cooled to room
temperature and acetic anhydride (19 cm3 in total) was added
portionwise to it. The exothermic reaction was maintained at
50–60 ЊC until bubbles (CO) were produced. The reaction mix-
ture was then allowed to stand at 60 ЊC for a further 15 min,
after which it was immediately poured into a well stirred ice–
water mixture (250 cm3). Crystals developed on storage of the
mixture and after 30 min were filtered off, and washed well with
water to give the title compound 4 which was air-dried to afford
a white crystalline solid (6.11 g, 88%); mp 112.5–116.5 ЊC
(as isolated); RF 0.6 (5:95, MeOH–CH2Cl2); δH (200 MHz;
CD3OD) 1.01 (3 H, s, 18-H), 1.10 (3 H, d, J 5.0, 21-H), 1.16 (3
H, s, 19-H), 4.85 (1 H, br m, w/2 10, 3-βH), 5.22 (1 H, m, w/2 10,
7-βH), 5.43 (1 H, m, w/2 8, 12-βH), 8.20 (1 H, s, CHO), 8.30 (1
H, s, CHO) and 8.37 (1 H, s, CHO).
(2S-cis)-2-Phenyl-1,3-dioxane-4-methanol 9
To a solution of (S)-butane-(Ϫ)-1,2,4-triol 8 (1.06 g, 10 mmol)
in cyclohexane (100 cm3) was added benzaldehyde16 (1.07 g, 10
mmol) and toluene-4-sulfonic acid hydrate (20 mg, 0.11 mmol).
The resulting mixture was heated under Dean–Stark conditions
for 7 h after which it was diluted with ether (30 cm3). The ether
extract was immediately washed with 1  aqueous sodium
carbonate (10 cm3) and water (5 cm3), dried (Na2SO4) and
evaporated to give the crude product as an oil, purification of
which by flash chromatography (ethyl acetate–hexane, 1:2)
furnished title compound 9 as a colourless oil (1.40 g, 72%); RF
0.40 (MeOH–CH2Cl2, 2:98); δH (200 MHz; CDCl3)13 1.37 (1
H, d, J 13.3, CHeq), 1.83 (1 H, ddt, 13.3, 12.3 and 5.25, CHax),
2.9 (1 H, s, OH), 3.6 (2 H, m, CH2OH), 3.8–4.0 (2 H, m, OCHax,
OCHCH2OH), 4.24 (1 H, ddd, J 11.4, 5.2 and 1.3, OCHeq), 5.48
(1 H, s, ArCH), 7.25–7.4 (3 H, m, ArH) and 7.4–7.5 (2 H, m,
ArH).
3á,7á,12á-Triformyloxy-22–iodo-23,24-bisnor-5â-cholane 5
A dry flask was charged with triformylnorcholic acid 4 (2.30 g,
4.81 mmol) and lead tetraacetate (2.75 g, 6.2 mmol) in dry CCl4
(100 cm3) and the mixture was stirred under N2 at reflux while
being irradiated with an Atlas 275 W IR lamp. Iodine (1.32 g,
5.2 mmol) dissolved in CCl4 (70 cm3) was added to the above
refluxing mixture and heated at reflux for a further 1.5 h. The
reaction mixture was then allowed to cool to room temperature
after which the resulting precipitate was filtered off and washed
with CCl4 (70 cm3). The combined filtrate and washings were
washed with 10% aqueous sodium thiosulfate, water, saturated
aqueous sodium hydrogen carbonate and finally with more
water. The solution was then dried (MgSO4), filtered and con-
centrated on a rotary evaporator to give the title compound 5
(2.45 g, 91%); mp 81–84 ЊC (as isolated); δH (200 MHz; CDCl3)
0.77 (3 H, s, 18-Me), 0.91–0.92 (6 H, m, 21-H and 19-H),
3.05–3.2 (2 H, m, 22-CH2), 4.7 (1 H, br m, w/2 20, 3-βH), 5.05
(1 H, m, w/2 10, 7-βH), 5.22 (1 H, m, w/2 8, 12-βH), 8.0
(1 H, s, CHO), 8.08 (1 H, s, CHO) and 8.18 (1 H, s, CHO)
(2S-cis)-2-Phenyl-1,3-dioxane-4-carbaldehyde 10
A solution of oxalyl chloride (0.91 g, 7.17 mmol) in dichloro-
methane (10 cm3) was stirred and cooled to Ϫ50 ЊC after which
DMSO (1.01 g, 12.9 mmol) was added to it, the temperature
being kept constant. The complex was allowed to form over 20
min after which time compound 9 (1.01 g, 5.23 mmol) in dry
dichloromethane (12 cm3) was added to it over 8 min at Ϫ50 ЊC.
J. Chem. Soc., Perkin Trans. 1, 1997
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Stirring was continued for a further 20 min after which time
triethylamine (3.27 g, 32.3 mmol) was added over 5 min to the
mixture which was then stirred and allowed to warm to room
temperature during 1 h. The mixture was poured into water (20
cm3) and the dichloromethane layer was separated and washed
with 20% aqueous sodium chloride (2 × 10 cm3), dried
(MgSO4) and evaporated to give an oil. Purification of this by
flash chromatography, using a stepwise elution of 15, 20, 30 and
100% dichloromethane in light petroleum afforded from
column fractions the CH2Cl2–light petroleum, 3:7 eluted with
the title compound 1013 initially as an oil before oligomerisation
occurred (502 mg, 50%); δH (200 MHz; CDCl3) 1.35–2.2 (2 H,
m), 3.6–4.6 (3 H, m), 5.3–5.7 (1 H, m) and 9.7 (0.5 H, s, CHO),
partially oligomerised.
CDCl3) 0.66 (3 H, s, 18-H), 0.85 (3 H, s, 19-H), 0.97 (3 H, d, J
5.6, 21-H), 3.40 (1 H, br m, w/2 22, 3-βH), 3.5–4.05 (4 H, m,
7-βH, OCH , 12-βH, OCHCH᎐), 4.06–4.32 (1 H, m, OCH ),
᎐
ax
eq
5.48 (1 H, s, ArCH) and 7.27–7.54 (5 H, m, ArH) [Found (FAB)
(Mϩ ϩ 1), 527.375 80. C33H51O5 requires 527.373 66].
(24R)-27-Nor-5â-cholestane-3á,7á,12á,24,26-pentol 14
A mixture of reduced benzylidene 13 (48.2 mg, 0.09 mmol) and
toluene-4-sulfonic acid hydrate (4.7 mg, 0.009 mmol) in metha-
nol (9 cm3) was stirred at room temperature for 24 h. The reac-
tion was quenched by addition of potassium carbonate (9 mg,
0.065 mmol) and evaporated to afford a crude solid. The crude
material was redissolved in a little methanol to which silica (2
g) was then added; methanol was again removed by evapor-
ation. The silica was added to the top of a silica column and the
reaction product purified by flash chromatography using a
stepwise elution of 5, 10, 15 and 20% methanol in dichloro-
methane. Title compound 14 was eluted in 15% methanol and
was contaminated with some toluene-4-sulfonic acid which was
washed out by dissolving in ethyl acetate–butanol (1:1) (5 cm3)
and washing with potassium carbonate (3 × 0.5 cm3) and water
(5 cm3). The organic phase was dried (MgSO4) and evaporated
to give pure ranol 14 (28.5 mg, 71%) as a crystalline solid; RF
0.35 (15:85, MeOH–CH2Cl2); δH (200 MHz; [2H5]pyridine)
0.85 (3 H, s, 18-H), 1.03 (3 H, s, 19-H), 1.27 (3 H, d, J 5.4, 21-
H), 3.77 (1 H, br m, w/2 18, 3-βH), 4.12 (1 H, m, w/2 11, 7-βH),
4.25 (2 H, t, 26-CH2OH) and 4.29 (1 H, m, w/2 12, 12-βH)
(24R)-24,26-O-Benzylidene-3á,7á,12á,24,26-pentahydroxy-27-
nor-5â-cholest-22(Z)-ene 12a and 22(E)-ene 12b
A solution of triphenylphosphonium iodide 7 (719 mg, 0.97
mmol) in anhydrous ether (35 cm3) was stirred under N2 and
cooled to 4 ЊC after which 1.37  phenyllithium (5.1 cm3, 7
mmol) in dry ether was added to it and the temperature kept
constant for 10 min. Stirring was continued for a further 1 h at
room temperature during which time the mixture turned a deep
orange colour, indicating formation of phosphorane. In a
second flask a solution of the carbaldehyde 11 (215 mg, 1.12
mmol) in dry ether (5 cm3) was prepared and stirred under N2.
The orange phosphorane solution was pressure siphoned with
N2 into the aldehyde 11 solution and a thick white slurry
resulted with the orange colour fading rapidly. The mixture was
stirred for a further 20 h after which time it was diluted with
dichloromethane (100 cm3) and worked up by washing with
water (2 × 15 cm3). The organic extract was dried (Na2SO4) and
evaporated to yield the crude product, purification of which by
flash chromatography using a stepwise elution of 1, 2, 3, 3.5, 4
and 5% methanol in dichloromethane afforded from column
fractions 21–27 (3.5% methanol) the E-olefin 12b (56.8 mg,
11%). Fraction 30 was further chromatographed on a silica gel
plate to give E-olefin 12b (2.6 mg); RF 0.63 (MeOH–CH2Cl2,
10:90) and Z-olefin 12a (5.2 mg); Rf 0.57 (MeOH–CH2Cl2,
10:90). Title compounds 12a and 12b from fractions 28–36
were obtained as glassy solids (67.1 mg, 8%).
Acknowledgements
This work was supported by a grant from McFarlane Labora-
tories (Aust) Pty Ltd, Melbourne, Australia. The authors thank
Dr R. Gary Amiet for NMR interpretation, Ms Nicolette
Kalafatis for technical laboratory support and Mr Stuart
Thomson for mass spectral analysis.
References
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Data for Z-olefin 12a: δH (200 MHz; CDCl3) 0.7 (3 H, s, 18-
H), 0.88 (3 H, s, 19-H), 1.04 (3 H, d, J 6.6, 21-H), 3.40 (1 H, br
m, w/2 22, 3-βH), 3.77–4.14 (3 H, m, 7-βH, 12-βH, OCHax),
5 T. A. Macrides, L. M. Naylor, N. Kalafatis, A. Shihata and
P. F. A. Wright, Fundam. Appl. Toxicol., 1996, 33, 31.
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presented in part at the 7th International Congress of Toxicology,
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8 K.-Y. Tserng and P. D. Klein, Steroids, 1976, 29, 635.
9 R. Monks and I. L. Thomas, J. Labelled Compd. Radiopharm., 1983,
20, 463.
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11 E. L. Eliel, Rec. Chem. Prog., 1961, 22, 129.
12 J. F. Normant, A. Alexakis, A. Ghribi and P. Mangeney,
Tetrahedron, 1989, 45, 507.
4.2–4.37 (1 H, m, OCH ), 4.58–4.77 (1 H, m, OCH-CH᎐), 5.34
᎐
eq
(1 H, d, J 4, 22-CH᎐CH), 5.37 (1 H, s, 23-CH᎐CH) and 7.26–
᎐
᎐
7.6 (5 H, m, ArH) [Found (FAB) (Mϩ Ϫ ArCO) 419.318 15.
C26H43O4 requires 419.316 13].
Data for E-olefin: 12b 0.69 (3 H, s, 18-H), 0.87 (3 H, s, 19-H),
1.08 (3 H, d, J 6.6, 21-H), 3.40 (1 H, br m, w/2 22, 3-βH), 3.85 (1
H, m, w/2 8, 7-βH), 3.90–4.05 (2 H, m, 12-βH, OCHax), 4.2–4.35
(2 H, m, OCH , OCHCH᎐), 5.46 (1 H, dd, J 15.5 and 5.7,
᎐
eq
22-CH᎐CH), 5.52 (1 H, s, ArCH), 5.58 (1 H, dd, J 15.5 and
᎐
7.7, 23-CH᎐CH), 7.25–7.53 (5 H, m, ArH) [Found (FAB)
᎐
(Mϩ Ϫ ArCO), 419.317 05. C26H43O4 requires 419.316 13].
13 M. Thiam, A. Slassi, F. Chastrette and M. Chastrette, Synth.
Commun., 1992, 22, 83.
14 F. H. Sangsari, F. Chastrette and M. Chastrette, Synth. Commun.,
1988, 18, 1343.
15 D. D. Perrin and W. L. F. Amarego, in Purification of Laboratory
Chemicals, 3rd edn., Pergamon, Oxford, 1988.
16 Washed with aqueous sodium carbonate, dried and vacuum
distilled under nitrogen.
(24R)-24,26-O-Benzylidene-27-nor-5â-cholestane-3á,7á,12á,
24,26-pentol 13
A mixture of platinum oxide catalyst (45 mg) in methanol (10
cm3) was flushed and stirred under an atmosphere of hydrogen
for 20 min. The E-12b and Z-12a olefin mixture (55.6 mg, 0.106
mmol) in methanol (2 cm3) was then added to the catalyst mix-
ture and stirred for 24 h under an atmosphere of hydrogen. A
further charge of platinum oxide (39 mg) was added to the
mixture and stirring continued under hydrogen for 24 h after
which the reaction mixture was filtered through Celite and
evaporated to afford title compound 13 as a glassy solid (53.5
mg, 96%); RF 0.63 (MeOH–CH2Cl2, 10:90); δH (200 MHz;
Paper 6/07850H
Received 19th November 1996
Accepted 13th January 1997
1356
J. Chem. Soc., Perkin Trans. 1, 1997