Towards synthesis of calysterols, marine sterols with cyclopropene moiety in the side chain: Synthesis of 26,27-Dinor-23H-isocalysterol

Article abstract of DOI:10.1135/cccc19981575

26,27-Dinor-23H-isocalysterol 24 has been synthesized in 19% yield (6 steps) from ethyl 6β-methoxy-3α,5-cyclo-5α-pregnan-21-oate (18). For construction of the side chain, alkylation of lithium salt of ester 18 with 1-bromo-1,2-dimethyl-c-3-iodomethyl-c-2-(trimethylsilyl)cyclopropane 16 was used. It has been shown that reduction of the ester group in position 21 and rearrangement of the 3,5-cyclosteroid system are compatible with the sidechain functionalities. It has been found that methylation of 1,1-dibromo-2-(trimethylsilyl)cyclopropane is accompanied by an rearrangement involving 1,2-migration of the trimethylsilyl group.

Full text of DOI:10.1135/cccc19981575

Synthesis of 26,27-Dinor-23H-isocalysterol
1575
TOWARDS SYNTHESIS OF CALYSTEROLS, MARINE STEROLS
WITH CYCLOPROPENE MOIETY IN THE SIDE CHAIN:
SYNTHESIS OF 26,27-DINOR-23H-ISOCALYSTEROL
1
2,
Alicja KUREK-TYRLIK , Kazimierz MINKSZTYM and Jerzy WICHA *
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warsaw,
Poland; e-mail: 1 alicja@aichf.edu.pl, 2 jwicha@ichf.edu.pl
Received April 24, 1998
Accepted June 15, 1998
Dedicated to Dr Jan Fajkos on the occasion of his 75th birthday.
26,27-Dinor-23H-isocalysterol 24 has been synthesized in 19% yield (6 steps) from ethyl 6β-methoxy-
3α,5-cyclo-5α-pregnan-21-oate (18). For construction of the side chain, alkylation of lithium salt of
ester 18 with 1-bromo-1,2-dimethyl-c-3-iodomethyl-c-2-(trimethylsilyl)cyclopropane 16 was used. It
has been shown that reduction of the ester group in position 21 and rearrangement of the 3,5-cyclos-
teroid system are compatible with the sidechain functionalities. It has been found that methylation of
1,1-dibromo-2-(trimethylsilyl)cyclopropane is accompanied by an rearrangement involving 1,2-migra-
tion of the trimethylsilyl group.
Key words: Steroids; Cyclopropanes; Cyclopropenes; Steroid side chain construction; Marine natural
products; Total synthesis.
Calysterols are a class of marine sterols1 of considerable interest because of their un-
usual structure and assumed biological function as a cell membrane component2. Calys-
terol (1) (first reported by the Napoli group3), and its isomers differing in the double
bond position: (23R)-23H-isocalysterol4 (2a) and (24S)-24H-isocalysterol5 (3), have
been isolated from the Mediterranean sponge Calyx niceaensis where they occur as the
principal sterol constituents. The 23-epimer of compound 2a, (23S)-23H-isocalysterol
(2b), together with compounds 1 and 3 and 5,6-dihydro derivatives of compounds 1, 2b
and 3, have been isolated from the Bahamas sponge Calyx podatypa6. Studies by Djer-
assi and coworkers on marine sterols have resulted in the elucidation of calysterol bio-
synthesis7 and have contributed a great deal to the understanding of their chemical and
spectral properties8.
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1576
Kurek-Tyrlik, Minksztym, Wicha:
Calysterols have not yielded to synthesis from a readily available steroid starting
material9. The difficulties in the unsuccessful attempts10 ensue mainly from the high
reactivity of the cyclopropene system11. On the other hand, the cyclopropene double
bond in these compounds is sterically shielded by the isopropyl group and the large
steroid fragment. This suggested that steric congestion may be another major obstacle
in assembling the properly functionalized, cyclopropene-containing side chain in syn-
thetic intermediates.
25
23 24
H
H
28
H
H
HO
HO
Calysterol 1
(23R)-23H-Isocalysterol 2a
H
H
H
H
HO
HO
(23S)-23H-Isocalysterol 2b
(24S)-24H-Isocalysterol 3
In work aimed at the synthesis of a representative calysterol we have chosen 23H-
isocalysterol (2, 23,28-cyclostigmasta-5,24(28)-dien-3β-ol) as the target compound
since both its C-23 epimers 2a and 2b are fully characterized. To handle the chemical
instability of the cyclopropene moiety, it was planned to introduce the double bond into
cyclopropane ring at the terminal stages of synthesis using a preformed cyclopropane
intermediate A (Scheme 1). Elimination of halogen atom and the adjacent trialkyl/aryl-
silyl group appeared most promising with regard to mildness of the reaction conditions12
although elimination of two halogen atoms (X and Y = halogen) could lead to the goal
as well13. Two alternative approaches to the intermediate A were considered: (i) con-
struction of the suitable cyclopropane precursor C and its coupling with steroid build-
ing block B and (ii) assembling the side chain stepwise which would involve
cyclopropanation of the double bond in the intermediate D; the latter would be prepared
from B via E.
In practical terms, it was expected that analytical monitoring of the intermediate A
(R = 2-propyl) would be extremely difficult due to the presence of several isomers
(3 stereogenic centers in the cyclopropane ring). Under these circumstances, a study on
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1577
synthesis of the model cyclopropene derivative 4 (with the hydroxy group and the
double bond in rings A and B protected) could provide a useful guidance. The respec-
tive intermediate A (R = Me) would be formed as a mixture of isomers. However,
elimination of XY would remove the stereogenic centers in the cyclopropane ring and
afford a single and relatively easy to characterize cyclopropene derivative (4). In this
paper we describe our studies on synthesis of compounds of type 4.
R
R
EtOOC
R
X
Y
X
I
H
H
H
H
+
Y
B
C
A
2, R = CH(CH )
3 2
4, R = Me
EtOOC
Y
Y
X = halogen
Y = trialkyl/arylsilyl group
R
H
R
H
D
E
SCHEME 1
Our first objective was the synthesis of iodide 16 (Scheme 2). Silylated propargylic
alcohol14 5 was transformed in the usual way into the highly crystalline trityl deriva-
tive15 6. The latter compound was subjected first to hydroalumination with diisobutyl-
Br
Br
SiMe
3
TrO
(ii)
(iii)
ROCH
(i)
SiMe
Me
2
3
R
H
Me
SiMe
3
5, R = H
6, R = Tr
7
8, R = OTr
9, R = OH
(iv)
(v)
10, R = OTs
11, R = I
8
(vi)
(vii)
SiMe
Me
Me
Br
3
Br
Me
Me
Br
(viii)
(ix)
Me
Me
+
+
TrO
TrO
TrO
X
SiMe
SiMe
Me
SiMe
3
3
3
14
15, X = OH
16, X = I
12
13
Tr = trityl
(i) TrCl/pyridine; (ii) a) diisobutylaluminium hydride/ether-toluene, b) MeLi/ether, c) MeI; (iii) CHBr ,
3
R
50% aq. NaOH, Cetrimide, EtOH/CH Cl ; (iv) MeOH, Amberlist ; (v) TsCl/pyridine; (vi) NaI/Me CO;
2
2
2
(vii) a) MeI/THF-HMPA, b) butyllithium/hexanes; (viii) MeOH, reflux; (ix) a) TsCl/pyridine, b) NaI/Me CO
2
SCHEME 2
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1578
Kurek-Tyrlik, Minksztym, Wicha:
aluminium hydride, then the intermediate was treated with methyllithium (to effect for-
mation of an “ate” complex) and then with methyl iodide16. Product 7 with Z configu-
ration of the double bond was obtained exclusively. Transformation of 7 into 8 was
conducted by the method of Makosza and Fedorynski17 using bromoform, 50% NaOH
and benzyltriethylammonium chloride or Cetrimid® as the phase-transfer catalyst.
Treatment of a solution of 8 and methyl iodide in tetrahydrofuran (THF) containing
hexamethylphosphoric triamide (HMPA) with 1-butyllithium at –95 °C according to the
general procedure of Kitatani et al.18 yielded a mixture of three products in 5.4 : 2.6 : 1
ratio (98%) which were separated by chromatography. To the major product, the struc-
tures 12 and 13 were assigned on the basis of their 1H NMR spectra. In the spectrum of
12, the cyclopropane proton signal appeared at δ 0.70 ppm, as dd, J = 7.6 and 6.4 Hz,
whereas the corresponding signal in the spectrum of 13, at δ 1.55 ppm, dd, J = 8.7 and
6.7 Hz. Chemical shifts of these protons are in agreement with those described for
similar compounds18a. Compound 13 decomposed on storage at –18 °C during a few
days in contrast to its isomer 12 which was virtually completely stable. Chemical insta-
bility of 13 supports the assigned structure with trans oriented and strongly interacting
by the push-pull mechanism bromine atom and the trimethylsilyl group.
The minor component of the mixture was devoid of bromine atoms. Its molecular
formula obtained from high resolution mass spectrum corresponded to the cyclo-
1
propene derivative 14. This structure was fully confirmed by H and 13C NMR meas-
urements, including C–C spin–spin coupling constants19.
Proportion of the methylation (12 and 13) to the rearrangement product (14)
depended upon the temperature, reaction scale and amount of HMPA. Thus, the reac-
tion at –78 °C afforded a larger amount of the cyclopropene derivative with the ratio of
12/13/14 being 3.1 : 2.2 : 1, starting from 0.6 mmol of 8 and 2.2 : 1.4 : 1, starting from
6 mmol of 8. When a mixture of 8 and methyl iodide was treated with BuLi (at –78 °C)
with no HMPA added, cyclopropene 14 was formed as the only product (isolated in
92% yield). However, all our attempts to exclude completely formation of 14 failed.
Mechanism of formation of cyclopropene 14 and the role HMPA in this reaction
deserve a comment. The postulated mechanism of debromination is illustrated in
Scheme 3. An anion-induced silyl group 1,2 migration is followed by bromide anion
elimination. The presence of HMPA in the reaction medium activates methyl iodide as
external electrophile whereas it does not affect significantly the carbon–silicon bond in 8.
Br
Me Si
3
Br
Me Si
3
Li
(i)
Li
SiMe
Me
3
8
TrO
TrO
TrO
-LiBr
Me
Me
14
(i) butyllithium/THF
SCHEME 3
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1579
This explains the crucial role of HMPA for the proportion of methylation and rear-
rangement products. When our work was in progress a mechanistically similar rear-
rangements occurring with a silyl group migration have been reported20.
Having in mind the synthesis of calysterols 2a and 2b, we have briefly examined
isopropylation of 8. With replacement of methyl iodide with isopropyl iodide or triflate
in the above discussed reaction (–95 °C, THF–HMPA), only the rearrangement product
14 was obtained. No trace of the isopropyl analogue of 12 could be detected.
Our next goal on the synthetic route was to remove the protecting trityl group in 12
and 13 and transform the respective alcohols into iodides 16. For these reactions, we
have used the crude mixture of alkylation products since the relative stereochemistry of
the bromine atom and the trimethylsilyl group in the cyclopropane ring had no conse-
quences for the final product stereochemistry.
Our initial attempts to cleave the trityloxy group in 12 and accompanying products
under conditions of acid-catalyzed hydrolysis yielded complex mixtures of products.
Ultimately, it was found that heating of the mixture of trityl ethers in anhydrous
methanol results in transestherification. Chromatography of the crude product gave tri-
1
tylmethyl ether and the desired alcohols 15 (5.2 : 1 ratio by H NMR, 74% yield). The
fate of the minor component in the starting mixture, 14, was not followed.
The mixture of alcohols was tosylated and the crude unstable tosylates were immedi-
ately subjected to the reaction with sodium iodide in acetone. The iodide 16 was ob-
1
tained in 61% yield (one isomer, as shown by H NMR).
With iodide 16 in hand the stage was set for the alkylation reaction. Ester 18
(Scheme 4), prepared as previously described21 was treated with lithium diisopropyl-
amide and then with 2 equivalents of 16 in the presence of HMPA. The reaction was
rather slow and was accompanied by decomposition of the iodide. However, the alkyl-
ation product 19 was obtained in sufficient yield (32%) to study further transformations.
Reduction of the ester group in 19 with diisobutylaluminium hydride yielded alcohol
20 which was further reduced into the methyl derivative 22 via tosylate 21. The signals
of C-21 protons in the NMR spectra of alcohol 20, tosylate 21 and the methyl deriva-
tive 22 indicated that the alkylation was completely stereoselective with respect to the
stereogenic center at C-20.
After obtaining the intermediate 22 with the pre-prepared cyclopropene unit, we ap-
proached removal of the protecting 3,5-cyclo-steroid system. Hydrolysis of methyl
ether 22 with 4-toluenesulfonic acid in aqueous dioxane under reflux22 yielded
smoothly the corresponding homoallylic alcohol 23.
It was of interest to investigate coupling of ester 18 with cyclopropene building
block at earlier stages of transformation. To this end, dibromide 8 was subjected to
methanolysis to give alcohol 9 which was then transformed into iodide 11 in the usual
way. Our attempts to couple ester 18 and iodide 11 under alkylation reaction conditions
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1580
Kurek-Tyrlik, Minksztym, Wicha:
were unsuccessful. The reaction was sluggish even at higher temperature (–20 to 0 °C);
the only product that could be isolated was ester 18 with bromine in position 20.
Finally, treatment of 23 with tetrabutylammonium fluoride followed by flash chro-
matography of the product provided the target calysterol analogue 24 (100% yield). In
1
its H NMR spectrum six proton singlet at δ 1.95 ppm appeared corresponding to the
methyl groups on the cyclopropene ring. The cyclopropene derivative 24 could be
stored as an oil for a few hours without a visible decomposition as could be judged
1
from its H NMR spectra.
Br
EtOOC
Me
Me
COOEt
O
H
H
(i)
(ii)
SiMe
3
18
17
AcO
19
(iii)
OMe
OMe
Br
24
Br
RH C
Me
Me
2
Me
Me
23
H
H
28
(viii)
SiMe
3
SiMe
3
HO
23
(ix)
OMe
20, R = OH
21, R = OTs
22, R = H
(vi)
H
(vii)
HO
24
21
(i) ref. ; (ii) a) lithium diisopropylamide/THF, b) 16, HMPA; (iii) diisobutylaluminium hydride/CH Cl -toluene;
2
2
(iv) TsCl/pyridine; (v) LiEt BH/THF; (vi) TsCl/pyridine; (vii) LiEt BH/THF; (viii) TsOH/aqueous dioxane;
3
3
(ix) tetrabutylammonium fluoride/THF
SCHEME 4
In conclusion, calysterol analogue 24 has been synthesized by a convergent route
involving separate preparation of cyclopropane building block 16. It has been shown
that reduction of the ester group into the methyl group (19→22) and the deprotection of
the 3,5-cyclo-steroid system (22→23) are compatible with the side chain functionality.
However, a low yield of the coupling of the steroid and cyclopropane building blocks
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1581
suggests using a stepwise construction of the side chain in an approach to 23H-iso-
calysterols. An interesting migration of the trimethylsilyl group in the cyclopropane
ring has been noted.
EXPERIMENTAL
Melting points were determined on a hot-stage apparatus and are uncorrected. NMR spectra were
1
recorded in CDCl3 solutions, H at 200 MHz and 13C at 50 MHz with Varian Gemini instrument and
1H at 500 MHz and 13C at 125 MHz with Bruker AMX. Chemical shifts are reported in ppm (δ-scale),
coupling constants (J) in Hz. IR spectra were recorded on Perkin–Elmer 1670 FT unit, wavenumbers in cm–1.
Mass spectra (electron impact, 70 eV) were taken on AMD 604 (AMD Intectra GmbH, Germany).
Anhydrous solvents were obtained by distillation from benzophenone ketyl (ether, THF) or calcium
hydride (dioxane, toluene). Air-sensitive reactions were performed in oven- or flame-dried glassware
under argon. Organic extracts were dried with anhydrous Na2SO4 and solvents were evaporated on a
rotary evaporator. Column chromatography was performed on Merck silica gel 60, 230–400 mesh,
and TLC on Merck aluminium sheets, silica gel 60 F254 G. Optical rotations were measured with a
Perkin–Elmer Model 141 polarimeter using a 1 ml capacity cell (10 cm path length) for CHCl3 solu-
tions and are given in 10–1 deg. For preparative HPLC, column Macherey–Nagel Duren Nucleosil®,
flow 8 ml/min, was used.
1-Trimethylsilyl-3-trityloxyprop-1-yne (6)
A mixture of tritylchloride (11.58 g, 41.5 mmol), pyridine (3.4 ml, 42 mmol), alcohol14 5 (5.35 g,
41.5 mmol) and CH2Cl2 (17 ml) was stirred at room temperature for 10 h. Then CH2Cl2 (180 ml),
cold aqueous 3% HCl (15 ml) and ice (ca 5 g) were added. The organic layer was separated and
washed successively with saturated aqueous NaHCO3 solution (20 ml) and water (45 ml). The solvent
was evaporated, the residue dissolved in hexane and filtered through silica gel (30 g) to give 6 (14.9 g,
pure by TLC). This product was crystallized from methanol (130 ml)/water (2 ml) and dried in high
vacuum to give 6 (11.57 g, 75%), m.p. 93–94 °C, identical in all respects with an authentic sample15.
(Z)-3-Trimethylsilyl-1-trityloxybut-2-ene (7)
To a stirred solution of 6 (3.7 g, 9.96 mmol) in ether (18 ml) a solution of 1.2 M diisobutylaluminium
hydride in toluene (10 ml, 11.95 mmol) was added dropwise at 4 °C and the mixture was stirred at
room temperature until the starting material was consumed (TLC, hexane/toluene/ethyl acetate 10 : 1 : 0.02,
ca 5 h). Then the mixture was cooled to 0–5 °C and was treated with 1.6 M methyllithium in ether
(8.1 ml, 12.95 mmol) followed (after 30 min) with methyl iodide (2.1 ml, 32.4 mmol). The mixture
was stirred at room temperature for 22 h and then heated at the reflux for 1 h. After cooling, the
reaction was quenched by careful by careful addition of ice water. The mixture was partitioned be-
tween ether (70 ml) and 1 M HCl (40 ml). The aqueous layer was extracted with ether (2 × 20 ml).
The combined organic extracts were washed with saturated aqueous NaHCO3 solution and water. The
solvent was evaporated and the residue was dissolved in hexane and filtered through silica gel (38 g)
1
to give 7 (3.6 g, 94%). An analytical sample was crystallized from methanol: m.p. 73–74 °C. H NMR
spectrum (200 MHz) : 0.12 (s, 9 H, (CH3)3Si); 1.82 (dt, J = 1.5, 1.3, 3 H, CH3); 3.61 (dq, J = 6.5,
1.3, 2 H, CH2); 6.31 (tq, J = 6.5, 1.7, 1 H, C=CH); 7.19–7.53 (m, 15 H, arom. H). 13C NMR spec-
trum (50 MHz): –0.85 ((CH3)3Si)); 24.31 (CCH3); 63.89 (CH2); 86.68 (PhC); 127.04 (Cp); 127.90
(Cm); 128.90 (Co); 138.48 (C=CH); 138.73 (C=CSi); 144.50 (Cipso). For C26H30OSi (386.61) calcu-
lated: 80.77% C, 7.82% H; found: 80.81% C, 7.79% H.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1582
Kurek-Tyrlik, Minksztym, Wicha:
1,1-Dibromo-2-methyl-r-2-trimethylsilyl-c-3-(trityloxymethyl)cyclopropane (8)
A mixture of 7 (2.55 g, 6.59 mmol), CH2Cl2 (3.5 ml), bromoform (2.3 ml, 26.4 mmol), Cetrimide (46 mg),
50% aqueous NaOH (2.85 g, 71.3 mmol) and ethanol (20 µl) was vigorously stirred (with a mechani-
cal stirrer) at room temperature for 1 h and then at 50 °C for 18 h and then it was cooled to __ °C
and partitioned between water (15 ml) and CH2Cl2 (50 ml). The aqueous layer was extracted with
CH2Cl2 (2 × 25 ml). The combined organic extracts were washed with HCl (3%, 2 ml) and then with
saturated aqueous NaHCO3 solution (3 ml) and water (20 ml). The solvent was evaporated and the
residue was dissolved in hexane and filtered through silica gel (30 g). The filtrate was concentrated
and the precipitate collected to give 8 (2 g, 68%). An analytical sample was recrystallized twice from
hexane, m.p. 149–151 °C. 1H NMR spectrum (200 MHz): 0.03 (s, 9 H, (CH3)3Si); 1.30 (s, 3 H,
CH3); 1.48 (dd, J = 7.4, 6.7, 1 H, CH); 3.23 (dd, J = 10.8, 6.7, 1 H, CH2); 3.40 (dd, J = 10.8, 7.4,
1 H, CH2); 7.20–7.53 (m, 15 H, arom. H). 13C NMR spectrum (50 MHz): 0.34 ((CH3)3Si); 24.43
(CH3CSi); 25.87 (CH3); 41.71 (CH); 44.77 (CBr2); 64.33 (CH2); 87.04 (Ph3C); 127.03 (Cp); 127.80
(Cm); 128.84 (Co); 144.50 (Cipso). Mass spectrum, m/z (%): 558 (M+); 481, 368, 243 (C6H5I3C+, 100);
165, 75. For C27H30Br2OSi (558.42) calculated: 58.07% C, 5.42% H; found: 58.19% C, 5.21% H.
1,1-Dibromo-c-3-hydroxymethyl-2-methyl-r-2-(trimethylsilyl)cyclopropane (9)
A mixture of 8 (2.33 g, 4.18 mmol), methanol (25 ml) and Amberlyst-15 (100 mg) was heated under
reflux for 1 h, cooled and the precipitate (Ph3COMe) was removed and washed with methanol. The
filtrate was evaporated and the residue was chromatographed on silica gel (20 g). Elution with hexane–ether,
(20 : 1), gave some additional Ph3COMe and elution with hexane–ether (6 : 1) afforded 9 (1.23 g,
1
93%). A sample was purified by sublimation at 65 °C/65 Pa), m.p. 103–104 °C. H NMR spectrum
(200 MHz): 0.23 (s, 9 H, (CH3)3Si); 1.33 (s, 3 H, CH3); 1.58 (dd, J = 9.1, 6.1, 1 H, CH); 3.79 (part B
of ABX system, J = 11.7, 6.1, 1 H, CH2); 3.87 (part A of ABX system, J = 11.7, 9.1, 1 H, CH2).
13C NMR spectrum (50 MHz): 0.70 (CH3Si); 25.08 (CH3CSi); 25.97 (CH3); 43.87 (CH); 44.54
(CBr2); 63.01 (CH2). IR spectrum: 3 640. For C8H16Br2OSi (316.1) calculated: 30.39% C, 5.11% H;
found: 30.39% C, 5.14% H.
1,1-Dibromo-2-methyl-c-3-tosyloxymethyl-r-2-(trimethylsilyl)cyclopropane (10)
A mixture of 9 (520 mg, 1.63 mmol), tosyl chloride (390 mg, 2 mmol) and pyridine (2 ml) was
stirred at 5 °C for 16 h and then partitioned between ether (25 ml) and ice-cold 4 M HCl (8 ml). The
aqueous layer was extracted with ether (2 × 20 ml) and the combined organic extracts were washed
with saturated aqueous NaHCO3 solution and brine. The solvent was evaporated and the residue was
1
chromatographed on silica gel (10 g, 0.3% of ethylacetate in hexane) to give 10 (480 mg, 62%). H NMR
spectrum (200 MHz): 0.19 (s, 9 H, (CH3)3Si); 1.28 (s, 3 H, CH3); 1.59 (dd, J = 7.8, 7.6, 1 H, CH);
2.46 (s, 3 H, tosyl); 4.15 (dd, J = 10.8, 7.6, 1 H, CH2); 4.34 (dd, J = 10.8, 7.8, 1 H, CH2); 7.36 (d,
J = 8.6, 2 H, tosyl); 7.83 (d, J = 8.6, 2 H, tosyl). C15H22Br2O3SSi (470.3) calculated: 38.31% C,
4.72% H; found: 38.60% C, 4.72% H.
1,1-Dibromo-c-3-iodomethyl-2-methyl-r-2-(trimethylsilyl)cyclopropane (11)
A mixture of 10 (470 mg, 1 mmol), NaI (220 mg, 1.5 mmol) and acetone (16 ml) was heated under
reflux for 2 h. After cooling, the solvent was evaporated and the residue was chromatographed on
silica gel (10 g, hexane) to give 11 (360 mg, 85%). 1H NMR spectrum (200 MHz): 0.30 (s, 9 H,
(CH3)3Si); 1.32 (s, 3 H, CH3); 1.80 (dd, J = 8.7, 7.6, 1 H, CH); 3.26 (dd, J = 10.1, 8.7, 1 H, CH2);
3.48 (dd, J = 10.1, 7.6, 1 H, CH2). 13C NMR spectrum (50 MHz): 0.88 ((CH3)3Si); 5.68 (CH2); 26.00
(CH3); 28.92 (CH3CSi); 45.41 (CH); 48.16 (CBr2). Mass spectrum, m/z (%): 347, 345 (M+ – Br,
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1583
<0.1); 301, 299, 297 (M+ – I, 0.2); 73 (Me3Si+, 100). For C8H15Br2ISi (426.0) calculated: 22.55% C,
3.55% H; found: 22.63% C, 3.69% H.
Reaction of Ester 18 with Iodide 11
To a solution of lithium diisopropylamide, prepared from diisopropylamine (39 µl, 0.28 mmol) and
1.6 M butyllithium in hexanes (175 µl, 0.28 mmol), in THF (250 µl) a solution of 18 (30 mg, 0.08
mmol) in THF (250 µl) was added at –78 °C. The mixture was stirred for 1 h and then a solution of
11 (80 mg, 0.19 mmol) in THF (100 µl) and HMPA (100 µl) was added. Stirring at –70 °C was
continued for 2.5 h and the mixture was set aside at 0 °C for 12 h. The reaction was quenched with
water and the product was extracted with hexane (2 × 20 ml). The solvent was evaporated and the
residue was chromatographed on SiO2 (1 g, toluene/hexane 2 : 1) to give ethyl (20 R/S)-bromo-6β-
methoxy-3α,5-cyclo-5α-pregnan-21-oate (10 mg, 30%) and a mixed fraction consisting of this pro-
duct and 18 (14 mg).
1
Ethyl (20 R/S)-bromo-6β-methoxy-3α,5-cyclo-5α-pregnan-21-oate. H NMR spectrum (200 MHz):
0.41 (dd, J = 8.1, 5.2, 1 H, 4α-H); 0.62 (t, J = 4.4, 1 H, 4β-H); 0.74 (s, 3 H, 3 × 18-H); 0.98 (s, 3 H,
3 × 19-H); 1.29 (t, J = 7.1, 3 H, CH3CH2O); 2.72–2.77 (m, 1 H, 6-H); 3.30 (s, 3 H, CH3O); 4.14 (d,
J = 9.1, 1 H, CHBr); 4.18 (dq, J = 7.1, 1.3, 2 H, CH3CH2O). IR spectrum (film): 1 740, 1 755. Mass
spectrum, m/z (%): 454, 452 (M+, 27); 439, 437 (M+ – CH3, 57); 422, 420 (M+ – CH3OH, 59); 399,
397 (M+ – C4H7, 100); 359 (M – Br – CH3, 12); 342 (M+ – Br – CH3OH, 54).
Methylation of Dibromocyclopropane 8
To a mixture of 8 (136 mg, 0.24 mmol), HMPA (270 µl, 1.6 mmol), methyl iodide (126 µl, 1.92 mmol)
and THF stirred at –95 °C, (1.8 ml) 1.4 M butyllithium in hexanes (345 µl, 0.48 mmol) was added.
After 2 h at –95 °C ether (5 ml) was added followed by water (0.5 ml). The mixture was partitioned
between ether (20 ml) and water (15 ml). The aqueous layer was extracted with ether (20 ml). The
combined extract was evaporated and the residue was dissolved in hexane and filtered through silica
gel (1.5 g) to give a mixture of 12, 13 and 14 in a ratio of 5.4 : 2.6 : 1 (120 mg, 98%). The products
were separated by preparative HPLC (0.2% ethylacetate in hexane, detection at λ 253 nm).
1
r-1-Bromo-1,2-dimethyl-c-2-trimethylsilyl-c-3-(trityloxymethyl)cyclopropane (12). Rt 17.49 min. H NMR
spectrum (200 MHz): –0.03 (s, 9 H, (CH3)3Si); 0.70 (dd, J = 7.6, 6.4, 1 H, CH); 1.06 (s, 3 H,
(CH3)CSi); 1.90 (s, 3 H, (CH3)CBr); 3.30 (dd, J = 10.0, 6.4, 1 H, CH2); 3.38 (dd, J = 10.0, 7.6, 1 H,
CH2); 7.15–7.55 (15 H, arom. H). 13C NMR spectrum (50 MHz): 0.52 ((CH3)3Si); 19.53 ((CH3)CSi);
20.14, 28.01 ((CH3)CBr) and ((CH3)CSi); 37.54 (CH); 49.20 ((CH3)CBr); 65.40 (CH2); 86.79 (Ph3C);
126.88 (Cp); 127.69 (Cm); 128.84 (Co); 144.38 (Cipso). Mass spectrum, m/z (%): 494, 492 (M+); 382,
332, 243 (Ph3C+, 100); 165 (25); 73 ((CH3)3Si+, 52). HR MS, for C28H33BrOSi calculated:
492.14840; found: 492.14791.
r-1-Bromo-1,2-dimethyl-t-2-(trimethylsilyl)-t-3-(trityloxymethyl)cyclopropane (13). Rt 16.76 min.
1H NMR spectrum (200 MHz): –0.13 (s, 9 H, (CH3)3Si); 1.32 (s, 3 H, (CH3)CSi); 1.55 (dd, J = 8.7,
6.7, 1 H, CH); 1.70 (s, 3 H, CH3CBr); 2.96 (dd, J = 9.9, 6.7, 1 H, CH2); 3.17 (dd, J = 9.9, 8.7, 1 H,
CH2); 7.15–7.50 (15 H, arom. H). 13C NMR spectrum (50 MHz): 0.38 ((CH3)3Si); 19.28 ((CH3)CSi);
25.49, 26.38 ((CH3)CSi) and ((CH3)CBr); 39.31 (CH); 50.81 ((CH3)CBr); 61.95 (CH2); 86.57
(Ph3C); 126.96 (Cp); 127.79 (Cm); 128.66 (Co); 144.15 (Cipso).
1
1-Methyl-2-(trimethylsilyl)-3-(trityloxymethyl)cyclopropene (14). Rt 15.90 min. H NMR spectrum
(200 MHz): 0.13 (s, 9 H, (CH3)3Si); 1.59 (dd, J = 5.6, 4.5, 1 H, CHCH2O); 2.21 (s, 3 H, CH3); 2.77
1
(dd, J = 9.2, 4.5, 1 H, CH2); 2.99 (dd, J = 9.2, 5.6, 1 H, CH2); 7.15–7.50 (m, 15 H, arom. H). H NMR
spectrum (200 MHz, dioxane-d8): 0.14 (s, 9 H, (CH3)3Si); 1.59 (dd, J = 5.7, 4.3, 1 H, CHCH2O);
2.18 (s, 3 H, CH3); 2.71 (dd, J = 9.2, 4.5, 1 H, CH2); 3.02 (dd, J = 9.2, 5.7, 1 H, CH2); 7.10–7.60 (m, 15 H, arom. H).
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1584
Kurek-Tyrlik, Minksztym, Wicha:
13C NMR spectrum (50 MHz, dioxane-d8): –0.86 ((CH3)3Si); 13.48 (CH3); 20.25 (CHCH2); 72.07
(CH2); 86.64 (Ph3C); 112.87 ((CH3)3SiC); 127.31 (Cp); 128.22 (Cm); 129.39 (Co); 135.84 (C=C–C);
145.60 (Cipso). IR spectrum (film): 1 810. Mass spectrum, m/z (%): 398 (M+); 368 (M+ – 2(CH3));
243 (75, Ph3C+); 165 (65); 155 (M+ – Ph3C, 40); 125 (M+–Ph3COCH2, 72); 73 ((CH3)3Si+, 100). HR MS,
for C27H30OSi calculated: 398.20659; found: 398.20655.
An analogous reaction carried out at –78 °C yielded compounds 12, 13 and 14 in a ratio of 3.1 : 2.2 : 1
(94%). Compound 13 was unstable on storage.
1-Methyl-2-trimethylsilyl-3-(trityloxymethyl)cyclopropene (14)
To a mixture of 8 (435 mg, 0.78 mmol), methyliodide (408 µl, 6.24 mmol) and THF (8 ml), stirred
at –78 °C, 1.4 M butyllithium in hexanes (1.39 ml, 1.95 mmol) was added dropwise during 10 min.
Stirring was continued for 1 h and then the reaction was quenched with ether (5 ml) and water (0.5 ml)
and the mixture was partitioned between ether (20 ml) and water (10 ml). The aqueous layer was
extracted with ether and the combined organic extract was evaporated. The residue was dissolved in
hexane and filtered through silica gel to give 14 (286 mg, 92%) identical with the product described
above.
r-1-Bromo-1,2-dimethyl-c-3-hydroxymethyl-c-2-(trimethylsilyl)cyclopropane (15a) and
r-1-Bromo-1,2-dimethyl-t-3-hydroxymethyl-t-2-(trimethylsilyl)cyclopropane (15b)
A mixture of 12, 13 and 14 (481 mg, in 3.8 : 2.5 : 1 ratio) obtained as described above, was dis-
solved in methanol (16 ml) and heated under reflux for 1 h. After cooling, the mixture was diluted
with toluene (15 ml) and concentrated on a rotary evaporator. The residue (ca 10 ml) was transferred
onto a silica gel (10 g) column. Elution of the column afforded: Ph3COCH3 and some unchanged
starting material (hexane/ethylacetate 25 : 1) and a mixture of 15a and 15b (156 mg, 74%) in 5.2 :
1
1 ratio by H NMR spectrum (hexane/ethyl acetate 20 : 1).
An analogous reaction of 12 (isolated by HPLC) yielded 68% of 15a.
r-1-Bromo-1,2-dimethyl-c-3-hydroxymethyl-c-2-(trimethylsilyl)cyclopropane (15a)
1H NMR spectrum (200 MHz): 0.18 (s, 9 H, (CH3)3Si); 0.83 (dd, J = 8.0, 6.8, 1 H, CH); 1.06 (s, 3 H,
(CH3)CSi); 1.90 (s, 3 H, (CH3)CBr); 3.81–3.91 (m, 2 H, CH2). IR spectrum (CHCl3): 3 620. Mass
spectrum, m/z (%): 237, 235 (M+ – CH3); 219, 217 (M+ – CH3 – H2O); 171 (M+ – Br); 162, 160 (M+ –
(CH3)3SiOH, 18); 81 (M+ – (CH3)3SiOH – Br, 100); 73 ((CH3)3Si+, 62). HR MS, for C8H16OBrSi
(M+ – CH3) calculated: 235.01538; found: 235.01542.
1-Bromo-1,2-dimethyl-c-3-iodomethyl-c-2-(trimethylsilyl)cyclopropane (16)
A mixture of alcohols 15a and 15b (in 5.2 : 1 ratio, 245 mg, 0.98 mmol) was dissolved in pyridine
(2.3 ml) and treated with tosyl chloride (206 mg, 1.08 mmol) at 0 °C. The mixture was set aside at
0 to 4 °C for 18 h and then was partitioned between ether (20 ml) and water (10 ml). The aqueous
layer was extracted with ether (20 ml). The combined organic extract was evaporated. The residue
was dissolved in acetone (7 ml), NaI (220 mg, 1.47 mmol) was added and the mixture was heated
under reflux for 1.5 h. The solvent was evaporated and the residue was transferred with pentane onto
1
a silica gel (8 g) column. Elution of the column with pentane gave iodides 16 (215 mg, 61%). H NMR
spectrum (200 MHz): 0.22 (s, 9 H, (CH3)3Si); 1.07 (s, 3 H, (CH3)CSi); 1.08 (t, J = 7.9, 1 H, CH);
1.87 (s, 3 H, (CH3)CBr); 3.44 (d, J = 7.9, 2 H, CH2). 13C NMR spectrum (50 MHz): 0.90 ((CH3)3Si);
9.35 (CH2); 24.57 ((CH3)CSi); 20.14, 27.36 ((CH3)CSi) and ((CH3)CBr); 41.57 (CH); 53.42
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1585
((CH3)CBr). Mass spectrum, m/z (%): 281 (M+ – Br); 235, 233 (M+ – I); 162, 161 (M+ – (CH3)3SiI);
81 (M+ – ((CH3)3SiI – Br, 100); 73 ((CH3)3Si+, 47). For C9H18BrISi (361.1) calculated: 29.93% C,
5.02% H; found: 29.98% C, 5.11% H.
(23R*,24R*,28R*)-Ethyl 24-Bromo-6β-methoxy-28-(trimethylsilyl)-3α,5:23,28-dicyclo-26,27-dinor-
5α-stigmastan-21-oate (19)
To a solution of lithium diisopropylamide prepared from diisopropylamine (52 µl, 0.37 mmol) and
1.38 M butyllithium in hexanes (270 µl) in THF (350 µl), stirred at –78 °C, a solution of 18 (68 mg,
0.182 mmol) in THF (540 µl) was added. The mixture was stirred at –78 °C for 1 h and a solution
of 16 (128 mg, 0.36 mmol) in THF and HMPA (500 µl and 370 µl, respectively) was added drop-
wise during 10 min. The mixture was stirred at –23 °C for 3 h and the reaction was quenched with
water (2 ml). The mixture was extracted with ether (3 × 20 ml) and the combined extracts were
washed with water and brine. The solvent was evaporated and the residue was chromatographed on
silica gel (3 g) to give: 16 (hexane), 19 (35.2 mg, 32%, hexane/toluene 3 : 1), 19 contamined with
18 (7.6 mg) and 18 contaminated with unidentified side products (33.6 mg, toluene–acetone 4 : 1).
Compound 19. 1H NMR spectrum (200 MHz): 0.14 (s, 9 H, (CH3)3Si); 0.76 (s, 3 H, 3 × 18-H);
0.99 (s, 6 H, 3 × 19-H and 3 × 29-H); 1.26 (m, 3 H); 1.85 (s, 3 H, 3 × 25-H); 2.70–2.80 (m, 1 H,
6-H); 3.30 (s, 3 H, CH3O); 4.10 (m, 2 H, CH3CH2O). IR spectrum (film): 1 730. Mass spectrum, m/z (%):
593, 591 (M+ – (CH3), 1.4); 563, 561 (M+ – Et, 1.4); 547 (1); 527 (47); 513 (4); 446 (77); 431 (6);
373 (6); 353 (4); 349 (5); 279 (4); 267 (7); 253 (78); 239 (8); 277 (9); 213 (12); 199 (100); 173 (9);
159 (10); 149 (8); 140 (15); 133 (6); 121 (8); 105 (7); 95 (8); 81 (9); 73 (30). HR MS, for
C32H52O3BrSi (M+ – CH3) calculated: 591.28691; found: 591.28639.
(23R*,24R*,28R*)-24-Bromo-6β-methoxy-28-(trimethylsilyl)-3α,5:23,28-dicyclo-26,27-dinor-5α-
stigmastan-21-ol (20)
To a stirred solution of 19 (116 mg, 0.19 mmol) in CH2Cl2 (3.2 ml) 0.75 M diisobutylaluminium
hydride in toluene (1 ml, 0.75 mmol) was added at –23 °C. Stirring at –23 °C was continued for 45 min
and the reaction was quenched with ether (10 ml) and water (15 ml). The aqueous layer was extracted
with ether (3 × 25 ml) and the combined organic extracts were washed with brine. The solvent was
evaporated and the residue was chromatographed on silica gel (10 g, 0.6% acetone in hexane) to give 20
(96.5 mg, 90%). 1H NMR spectrum (200 MHz): 0.15 (s, 9 H, CH3Si); 0.44 (dd, J = 8.0, 4.5, 1 H,
4α-H); 0.66 (t, J = 4.5, 1 H, 4β-H); 0.76 (s, 3 H, 3 × 18-H); 1.01 (s, 3 H, 3 × 19-H); 1.05 (s, 3 H, 3 × 29-H);
1.88 (s, 3 H, 3 × 25-H); 2.72–2.79 (m, 1 H, 6-H); 3.31 (s, 3 H, CH3O); 3.65–3.90 (m, 2 H, CH2OH).
IR spectrum (film): 3 480. Mass spectrum, m/z (%): 566, 564 (M+, 0.3); 551, 549 (M+ – CH3, 0.2); 534,
532 (M+ – CH3OH, 0.1); 519, 517 (M+ – CH3 – CH3OH, 0.2); 511, 509 (M+ – C4H7, 0.4); 484 (12);
469 (53); 453 (3); 437 (2); 411 (42); 397 (9); 357 (2); 308 (3); 281 (3); 253 (40); 239 (5); 227 (7);
213 (9); 197 (17); 183 (12); 170 (55); 155 (100); 141 (15); 125 (22); 107 (19); 95 (19); 84.82 (18);
73 (58); 67 (16); 55 (12). HR MS, for C27H46O2BrSi (M+ – C4H7) calculated: 509.24509; found
509.24474.
(23R*,24R*,28R*)-24-Bromo-6β-methoxy-21-tosyloxy-28-(trimethylsilyl)-3α,5:23,28-dicyclo-26,27-
dinor-5α-stigmastane (21)
A mixture of 21 (41 mg, 0.073 mmol), pyridine (50 µl, 0.63 mmol), tosyl chloride (43 mg, 0.146 mmol)
and CH2Cl2 (0.5 ml) was stirred at room temperature for 16 h and then partitioned between ether (20 ml)
and water (5 ml). The aqueous layer was extracted with ether (20 ml) and the combined organic
extract was washed with water and brine. The solvent was evaporated and the residue was filtered
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1586
Kurek-Tyrlik, Minksztym, Wicha:
through silica gel (3 g, 0.7% of acetone in hexane) to give 21 (49.6 mg, 94%). 1H NMR spectrum
(200 MHz): 0.12 (s, 9 H, (CH3)3Si); 0.41 (dd, J = 7.9, 5.2, 1 H, 4α-H); 0.66 (s, 3 H, 3 × 18-H); 0.87
(s, 3 H, 3 × 29-H); 0.98 (s, 3 H, 3 × 19-H); 1.70 (s, 3 H, 3 × 25-H); 2.41 (s, 3 H, tosyl); 2.70–2.78
(m, 1 H, 6-H); 4.14 (q, J = 9.6, 2 H, CH2OTs); 7.31 (d, J = 8.2, 2 H, tosyl); 7.80 (d, J = 8.2, 2 H,
tosyl). Mass spectrum, m/z (%): 718 (M+, 0.1); 705, 703 (M+ – CH3, 0.1); 689, 687 (0.1); 673, 671
(0.4); 663, 665 (0.1); 638 (0.4); 623 (0.2); 606 (0.2); 593, 591 (0.2); 583 (0.2); 565 (2); 557 (0.3);
551 (0.4); 534 (0.4); 511 (0.7); 499, 501 (0.6); 466 (5); 427 (12.5); 411 (3); 395 (3); 379 (3.5); 361,
363 (3.5); 281 (7); 267 (7); 259 (7); 253 (100); 245 (5); 239 (4); 229 (17); 213 (12); 199 (9); 185
(8); 171 (8); 159 (17); 147, 145 (17); 133 (16); 121 (19); 107 (24); 95 (14); 91 (15); 81 (15); 81
(15); 73 (51); 66 (22).
(23R*,24R*,28R*)-24-Bromo-6β-methoxy-28-(trimethylsilyl)-3α,5:23,28-dicyclo-26,27-dinor-5α-
stigmastane (22)
To a solution of 21 (18.7 mg, 0.026 mmol) in THF (0.4 ml), 1 M LiEt3BH (Super Hydride®) in THF
(0.1 ml, 0.1 mmol) was added at 0 °C. The mixture was stirred at 0 °C for 4.5 h and the reaction was
quenched with ether (10 ml) and water (10 ml). The aqueous layer was extracted with ether (2 × 20 ml),
and the combined organic extracts were washed with water and brine, the solvent was evaporated and
1
the residue was filtered through silica gel (1.5 g, hexane/toluene 6 : 1) to give 22 (11 mg, 77%). H NMR
spectrum (200 MHz): 0.19 (s, 9 H, (CH3)3Si); 0.39–0.52 (m, 2 H, 4α-H and 23-H); 0.67 (t, J = 4.6,
1 H, 4β-H); 0.78 (s, 3 H, 3 × 18-H); 1.02 (d, J = 6.4, 3 H, 3 × 21-H); 1.05 (s, 3 H, 3 × 19-H); 1.08
(s, 3 H, 3 × 29-H); 1.91 (s, 3 H, 3 × 25-H); 2.76–2.84 (m, 1 H, 6-H); 3.35 (s, 3 H, CH3O). IR
spectrum (film): 2 970, 2 890, 1 450, 1 380, 1 245, 1 090, 830. Mass spectrum, m/z (%): 548 (M+,
0.1); 535, 533 (M+ – CH3, 0.2); 518, 516 (M+ – CH3OH, 0.1); 503, 501 (M+ – CH3OH – CH3, 0.5);
495, 493 (M+ – C4H7, 0.3); 468 (2); 453 (0.6); 437, 436 (1); 421 (0.4); 413 (0.9); 396, 395 (1); 381
(3); 364, 363 (2); 349 (2); 341 (4); 335 (0.5); 328 (0.9); 314 (1.6); 311 (0.6); 307 (0.6); 299 (4); 283
(10); 267 (4); 259 (7); 253 (100); 241 (3); 227 (7); 213 (8); 201, 199 (6); 187 (6); 173 (6); 159 (10);
154 (8); 147, 145 (11); 139 (8); 133 (9); 121 (13); 109 (16); 95 (10); 81 (13); 73 (48); 67 (28). HR
MS, for C31H53OBrSi (M+ – CH3) calculated: 533.2814; found: 533.2815.
(23R*,24R*,28R*)-24-Bromo-28-(trimethylsilyl)-23,28-cyclo-26,27-dinorstigmast-5-en-3β-ol (23)
A solution of 22 (11 mg, 0.02 mmol) in a mixture dioxane–water 4 : 1 (3 ml) containing a catalytic
amount of 4-toluenesulfonic acid, was heated under reflux for 3 h. After cooling, the mixture was
diluted with ether (25 ml). The aqueous layer was extracted with ether (25 ml) and the combined
organic extract was washed with water and brine. The solvent was evaporated and the residue was
1
chromatographed on silica gel (1 g, hexane/ether 6 : 1) to give 23 (10 mg, 93%). H NMR spectrum
(200 MHz): 0.14 (s, 9 H, (CH3)3Si); 0.42 (dd, J = 9.2, 3.8, 1 H, 23-H); 0.69 (s, 3 H, 3 × 18-H); 0.97
(d, J = 5.3, 3 H, 3 × 21-H); 0.99 (s, 3 H, 3 × 19-H); 1.04 (s, 3 H, 3 × 29-H); 1.87 (s, 3 H, 3 × 25-H);
3.40–3.60 (m, 1 H, 3-H); 5.33 (d, J = 5.2, 1 H, 6-H). IR spectrum (CHCl3): 3 620. Mass spectrum,
m/z (%): 534 (M+, 0.04); 521, 519 (M+ – CH3, 0.1); 503, 501 (M+ – CH3OH, 0.4); 454 (M+ – HBr, 5);
439 (0.8); 421 (0.4); 381 (1.6); 367 (3); 353 (1); 349 (2); 343 (0.4); 335 (0.3); 325 (0.7); 314 (4);
300 (10); 283 (10); 271 (80); 253 (16); 241 (6); 227 (4); 213 (10); 199 (5); 187 (7); 173 (8); 159 (21);
154 (23); 145 (17); 139 (12); 133 (22); 121 (17); 109 (25); 95 (17); 81 (24); 73 (100); 67 (48); 55 (11);
41 (6). HR MS, for C29H48OBrSi (M+ – CH3) calculated: 519.26578; found 519.26586.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Synthesis of 26,27-Dinor-23H-isocalysterol
1587
23,28-Cyclo-26,27-dinorstigmast-5,23(28)-dien-3β-ol (24)
To a solution of 23 (3.7 mg, 0.007 mmol) in THF (1 ml) tetrabutylammonium fluoride (26 mg, 0.08 mmol)
was added and the mixture was stirred at room temperature for 20 h and then heated under reflux for
1 h. After cooling, the mixture was partitioned between ether (20 ml) and water (5 ml). The aqueous
layer was extracted with ether (2 × 20 ml) and the combined organic extracts were washed with
water and brine. The solvent was evaporated and the residue was chromatographed on silica gel (1 g,
hexane/ether 6 : 1) to give 24 (3.3 mg, 100%). 1H NMR (200 MHz): 0.67 (s, 3 H, 3 × 18-H); 0.98
(d, J = 4.9, 3 H, 3 × 21-H); 0.99 (s, 3 H, 3 × 19-H); 1.95 (s, 6 H, 2 × =C–CH3); 3.40–3.60 (m, 1 H,
3-H); 5.33 (d, J = 5.3, 1 H, 6-H). Mass spectrum, m/z (%): 382 (3, M+); 367 (M+ – CH3, 3); 364 (M+ – H2O,
0.7); 353 (0.9); 349 (M+ – CH3 – H2O, 2); 339 (0.3); 336 (0.3); 325 (0.5); 312 (2); 300 (8); 297 (2);
283 (17); 271 (100); 267 (10); 253 (16); 241 (7); 227 (6); 215, 213 (11); 199 (6); 187 (8); 173 (11);
159 (26); 145 (20); 132 (26); 121 (16); 109 (27); 95 (19); 81 (3); 67 (64); 55 (14); 41 (10). HR MS,
for C27H42O (M+) calculated: 382.32356; found: 382.32356.
REFERENCES AND NOTES
1. Falkner D. J.: Nat. Prod. Rep. 1991, 8, 97.
2. Mena P. L., Djerassi C.: Chem. Phys. Lipids 1985, 37, 257.
3. Fattorusso E., Magno S., Mayol L., Santacroce C., Sica D.: Tetrahedron 1975, 31, 1715.
4. Li L. N., Li L. H.-t., Lang R. W., Itoh T., Sica D., Djerassi C.: J. Am. Chem. Soc. 1982, 104,
6726.
5. Itoh T., Sica D., Djerassi C.: J. Org. Chem. 1983, 48, 890.
6. Doss G. A., Djerassi C.: J. Am. Chem. Soc. 1988, 110, 8124.
7. Djerassi C., Silva C. J.: Acc. Chem. Res. 1991, 24, 371; and references therein.
8. For an example, see: Itoh T., Djerassi C.: J. Am. Chem. Soc. 1983, 105, 4407.
9. A preliminary communication on our synthesis of calysterols has been published: Kurek-Tyrlik
A., Minksztym K., Wicha J.: J. Am. Chem. Soc. 1995, 117, 1849.
10. a) Steiner E., Djerassi C., Fattorusso E., Magno S., Mayol L., Santacroce C., Sica D.: Helv.
Chim. Acta 1977, 60, 475. b) For a review on sterol side chain construction, see: Piatak D. M.,
Wicha J.: Chem. Rev. 1978, 78, 199.
11. For reviews on cyclopropenes, see: a) Closs G. L. in: Advances in Alicyclic Chemistry (H. Hart
and G. J., Karabatsos, Eds), Vol. 1., p. 53. Academic Press, New York 1966; b) Halton B.,
Banwell M. G. in: The Chemistry of the Cyclopropyl Group (S. Patai and Z. Rappoport, Eds),
Vol. 2, Chap. 21. Wiley, Chichester 1987; c) Baird M. S.: Top. Curr. Chem. 1988, 144, 137.
12. For some examples, see: a) Billups W. E., Lin L.-J., Arney B. E., Jr., Rodin W. A., Casserly E.
W.: Tetrahedron Lett. 1984, 25, 3935; b) Chan T. H., Massuda D.: Tetrahedron Lett. 1975, 3383.
13. a) Baird M. S., Fitton H. L., Clegg W., McCamley A.: J. Chem. Soc., Perkin Trans. 1 1993, 321;
b) Wiberg K. B., Artis D. R., Bonneville G.: J. Am. Chem. Soc. 1991, 113, 7969; c) Dent B. R.,
Halton B., Smith A. M. F.: Aust. J. Chem. 1986, 39, 1621; d) Baird M. S., Hussain H. H.,
Nethercott W.: J. Chem. Soc., Perkin Trans. 1 1986, 1845.
14. Jones T. K., Denmark S. E.: Org. Synth. 1986, 64, 182.
15. Achmatowicz B., Raubo P., Wicha J.: J. Org. Chem. 1992, 57, 6593.
16. a) Eisch J. J., Damsevitz G. A.: J. Org. Chem. 1976, 41, 2214; b) Uchida K., Utimoto K., Nozaki H.:
J. Org. Chem. 1976, 41, 2215; c) See also: Oda H., Sato M., Morizawa Y., Oshima K., Nozaki H.:
Tetrahedron 1985, 41, 3257.
17. a) Makosza M., Fedorynski M.: Synth. Commun. 1973, 3, 305; b) See also: Doss G. A., Silva C. J.,
Djerassi C.: Tetrahedron 1989, 45, 1273.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

1588
Kurek-Tyrlik, Minksztym, Wicha:
18. a) Kitatani K., Hiyama T., Nozaki H.: Bull. Chem. Soc. Jpn. 1977, 50, 3288; b) For a review,
see: Kostikov R. R., Molchanow A. P., Hopf H.: Top. Curr. Chem. 1990, 155, 41.
19. Jankowski P., Kamienska-Trela K., Minksztym K., Wicha J.: J. Organomet. Chem. 1993, 460, 15.
20. a) Baird M. S., Dale C. M., Al-Dulayyami J. R.: J. Chem. Soc., Perkin Trans. 1 1993, 1373; b)
Menichetti S., Griffiths G., Stirling C. J. M.: J. Chem. Soc., Chem. Commun. 1992, 54; c) Creary X.,
Wang Y.-X.: Tetrahedron Lett. 1989, 30, 2493; d) Krims M., Primke A. H., Stolhmeier M., de
Meijere A.: Rec. Trav. Chim. Pays-Bas 1986, 105, 462.
21. a) Wicha J., Bal K., Piekut S.: Synth. Commun. 1977, 7, 215; b) Zarecki A., Wicha J.: Synthesis
1996, 455.
22. Narwid T. A., Cooney K. E., Uskokovic M. R.: Helv. Chim. Acta 1974, 57, 771.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)