Synthesis of the C/D/E and A/B rings of xestobergsterol-(A)

Article abstract of DOI:10.1021/jo982319w

The A/B and the C/D/E rings of the xestobergsterol skeleton have been stereoselectively synthesized starting with testosterone and epiandrosterone, respectively. A deconjugative ketalization of the A-ring enone of testosterone provided a handle for functionalization of the B-ring. A stereoselective aldol condensation was used to incorporate the E-ring.

Full text of DOI:10.1021/jo982319w

J . Org. Chem. 1999, 64, 2475-2485
2475
Syn th esis of th e C/D/E a n d A/B Rin gs of Xestober gster ol-(A)
M. E. Krafft,* O. A. Dasse, and Z. Fu
Department of Chemistry, Florida State University, Tallahassee, Florida 32306-4390
Received November 24, 1998
The A/B and the C/D/E rings of the xestobergsterol skeleton have been stereoselectively synthesized
starting with testosterone and epiandrosterone, respectively. A deconjugative ketalization of the
A-ring enone of testosterone provided a handle for functionalization of the B-ring. A stereoselective
aldol condensation was used to incorporate the E-ring.
Marine sponges have been a rich source of new types
of steroids, typified by unique side-chain structures and
unusual functionalization. Recently, isolation of steroids
in a novel class, the xestobergsterols, has been reported,1
and these compounds showed strong pharmacological
properties. Our interest in the xestobergsterol steroids
was stimulated by their potent biological activity and the
challenging C/D/E ring system.
We have recently reported a synthesis of the C/D/E
skeleton of the xestobergsterols using an intramolecular
Pauson-Khand reaction (eq 1).3,4 Unfortunately, the key
Xestobergsterol-(A), 1, and xestobergsterol-(B), 2, are
unique pentacyclic steroids with unusual cis fused C/D
ring junctions. They were isolated in 1992 from the crude
extract of the Okinawan sponge Xestospongia bergquistia
Fromont.1 In 1995, xestobergsterol-(C), 3, was isolated
from the extracts of the Okinawan marine sponge Ircinia
sp.2 The structures were elucidated using primarily NMR
spectroscopic techniques. In 1995, reexamination of the
NMR spectroscopic data of xestobergsterol-(A), 1, and
xestobergsterol-(B), 2, by Kobayashi et al. resulted in a
revision of the configuration at C-23 and of the conforma-
tion of the C-ring in both 1 and 2.2 Xestobergsterol-(A),
1, and xestobergsterol-(C), 3, exhibit cytotoxicity against
cycloaddition step provided the pentacyclic steroid skel-
eton in only modest yield. This prompted us to pursue
an alternate route to the C/D/E portion of the skeleton.
In addition, we have now successfully synthesized the
A/B rings of xestobergsterol-(A). During the course of our
work, J ung and co-workers reported a synthesis of
7-deoxyxestobergsterol-(A) from stigmasterol using a ring
closing aldol to form the E-ring and a Breslow remote
functionalization reaction as key transformations.5
Our approach to the synthesis of the xestobergsterols
begins with a functionalization of commercially available
tetracyclic steroids. Testosterone, 4, and epiandrosterone,
5, proved to be suitable starting materials because they
provided not only a rapid entry into a substantial portion
of the carbon framework but also a source of the neces-
sary chirality.
L-1210 murine leukemia cells with IC50 values of 4.0 µg/
mL and 4.1 µg/mL, respectively.2 Additionally, xestoberg-
sterol-(A), 1, and xestobergsterol-(B), 2, have been shown
to strongly inhibit histamine release from rat peritoneal
mast cells induced by anti-IgE in a dose-dependent
manner.
Our original plan for the stereoselective synthesis of
the C/D/E portion of 1 is outlined in Scheme 1. We
(1) Shoji, N.; Umeyama, A.; Shin, K.; Takeda, K.; Arihara, S. J . Org.
Chem. 1992, 57, 2996.
(2) Kobayashi, J .; Shinonaga, H.; Shigemori, H. J . Nat. Prod. 1995,
58, 312.
(3) Krafft, M. E.; Chirico X. Tetrahedron Lett. 1994, 35, 4511.
(4) Krafft, M. E.; Shao, B.; Dasse, O. A Tetrahedron 1998, 54, 7033-
7044.
(5) J ung, M. E.; J ohnson, T. W. J . Am. Chem. Soc. 1997, 119, 12412.
10.1021/jo982319w CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/18/1999

2476 J . Org. Chem., Vol. 64, No. 7, 1999
Krafft et al.
Sch em e 1
Our plan was then to introduce a functionalized side-
chain by 1,4-cuprate addition to alkylidene epoxide 12
from the less sterically demanding R-face.9-11 However,
all attempts to stereo- and regioselectively introduce a
side chain moiety using cuprates 14-17 or allyl or vinyl
cuprates failed and only mixtures of 1,2- and 1,4-addition
adducts were obtained.
We turned our attention to an alternate approach for
the introduction of the side chain (Scheme 3). Addition
Sch em e 3
envisioned that we could introduce the side-chain, which
would be used to close the last ring, via a 1,4-nucleophilic
addition of a properly functionalized cuprate to alkylidene
epoxide 6, readily synthesized from epiandrosterone 5,
to give rise to keto-alcohol 7 (Scheme 1). Further hydro-
genation of the ∆16-steroid from the R-face, giving 8 with
the proper stereochemistry at C-17, oxidation and aldol
ring closure with concomitant C-14 epimerization would
then lead to the fully functionalized C/D/E ring system
of the xestobergsterols, i.e., 9.
Epoxidation of enone 104,6 on the â-face using tert-butyl
hydroperoxide in THF/H2O at 0 °C provided epoxyketone
11 in 85% yield (Scheme 2). Wittig olefination at 0 °C
Sch em e 2
of 2-lithio-2-methyl-1,3-dithiane to enone 18, obtained in
quantitative yield from epiandrosterone 5 via a Pd-
mediated trimethylsilyl enol ether oxidation, proceeded
smoothly (95% yield) at room temperature from the less-
hindered R-face.14 The resulting tertiary alcohol 19 was
then subjected to reaction with aqueous sulfuric acid in
(11) Normant, J . F.; Alexakis, A.; Cahiez, G. Synthesis 1978, 528.
(12) Corey, E. J .; Enders, D.; Bock, M. G. Tetrahedron Lett. 1976,
17, 7. Corey, E. J .; Enders, D. Tetrahedron Lett. 1976, 17, 3. Corey, E.
J .; Enders, D. Tetrahedron Lett. 1976, 17, 11. Yamamoto, K.; Iijima,
M.; Ogimura, Y. Tetrahedron Lett. 1982, 23, 3711.
(13) Gardette, M.; Alexakis, A.; Normant, J . F. Tetrahedron 1985,
41, 5887. Germon, C.; Alexakis, A.; Normant, J . F. Synthesis 1984,
43. Normant, J . F.; Cahiez, G.; Alexakis, A.; Villieras, J . Bull. Soc.
Chim. Fr. 1977, 693. Foulon, J . P.; Commercon-Bourgain, M.; Normant,
J . F. Tetrahedron 1986, 42, 1389. Normant, J . F.; Alexakis, A. Synthesis
1981, 841. Normant, J . F.; Cahiez, G.; Bourgain, M.; Chuit, C.;
Villieras, J . Bull. Soc. Chim. Fr. 1974, 1656. Lipshutz, B. H.; Sengupta,
S. Org. React. 1992, 41, 135.
provided a 9/1 mixture of desired epoxyalkene 12 and
isomer 13 in 80% yield. Although most reports on similar
steroids cite formation of the E-isomer only, we still de-
tected the Z-isomer under identical reaction conditions.7-10
(6) Ito, Y.; Hirao, T.; Saegusa, T. J . Org. Chem. 1978, 43, 1011.
(7) Moon, S.; Stuhmiller, L. M.; Chadha, R. J .; McMorris, T. C.
Tetrahedron 1990, 46, 2287.
(8) Takahashi, T.; Ootake, A.; Tsuji, J .; Tachibana, K. Tetrahedron
1985, 41, 5747.
(9) Marino, J . P.; Abe, H. J . Am. Chem. Soc. 1981, 103, 2907.
(10) Liu, D.; Stuhmiller, L. M.; McMorris, T. C. J . Chem. Soc., Perkin
Trans. 1 1988, 2161.
(14) Corey, E. J .; Crouse, D. J . Org. Chem. 1968, 33, 298. Corey, E.
J .; Erickson, B. W. J . Org. Chem. 1971, 36, 3553. J ones, J . B.;
Grayshan, R. Can. J . Chem., 1972, 50, 1414.

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)
J . Org. Chem., Vol. 64, No. 7, 1999 2477
Sch em e 4
THF to provide rearranged C-15 hydroxylated pregnane
derivative 21 in 80% yield along with diene 20 (10%
yield). The hydrolysis was best performed with 300 mol
% of sulfuric acid. An increase in acid concentration
resulted in extensive diene formation. It is not clear
whether diene 20 arises directly from tertiary alcohol 19
or from alcohol 21. The stereochemistry at C-15 was
1
determined by a combination of H NMR DQCOSY and
NOESY experiments. The substitution reaction leading
to alcohol 21 can occur by either a syn SN2′ or SN1
pathways. The high stereoselectivity of an addition would
tend to point toward a syn-SN2′ pathway;15 however, it
is known that the addition of alcohols to the C-15 enone
position results in the stereoselective formation of 15â-
ethers.16
Deprotection of the masked ketone proved to be chal-
lenging. Attempts to hydrolyze dithiane 21 using MeI/
THF/water17 resulted in extensive formation of dienone
23, presumably due to HI-catalyzed hydrolysis. Addition
of solid bicarbonate resulted in only a small amount of
dithiane cleavage and mostly recovered starting material.
Enone 22 was obtained in 40% yield along with other
products when the thioketal was cleaved by reaction with
NCS/AgNO3/THF/CH3CN/H2O18,19 or iodine/ether/sodium
bicarbonate.20 Deprotection with thallium nitrate in
MeOH/THF proved to be suitable conditions and provided
dihydroxyenone 22 in satisfactory yield (62%).21,22 Selec-
tive protection of the 3â-hydroxyl group with tert-bu-
tyldimethylsilyl trifluoromethanesulfonate in pyridine/
methylene chloride at -78 °C provided hydroxyenone 24
in 91% yield.23 Further hydrogenation (1 atm H2, ambient
temp, EtOH) from the more accessible R-face using
rhodium/alumina as a catalyst provided hydroxyenone
25 in quantitative yield.8,24,25 The stereochemistry at C-17
Further oxidation of the C-15 alcohol with PCC in
methylene chloride gave a 1:1 mixture of diones 29a and
29b, epimeric at the C-20 methyl group (86% yield).27,28
Examination of a molecular model for the aldol reaction
revealed that, in the case of the C-20 nonnatural epimer
29b, a very severe 1,3-C-13 methyl to C-20-methyl
interaction on the concave face of the bicyclo[3.3.0]octane
ring system would develop in the transition state. For
natural epimer 29a , the C-20 methyl group is placed on
the convex face of the bicyclo[3.3.0]octane therefore
eliminating the significant steric interaction (Figure 1).
1
was determined by a combination of H NMR DQCOSY
and NOESY experiments. Attempts to carry out the
hydrogenation with other catalysts such as Pd/C or PtO2
resulted in extensive hydrogenolysis of the allylic 15â-
alcohol. We did not observe any hydrogenolysis when the
rhodium/alumina catalyst was used. At this point, we
have now introduced the correct functionalization at
C-15, set the stereochemistry at C-17, and can use the
C-20 ketone as a handle for elaboration of the side-chain.
Wittig olefination of hydroxyketone 25 provided nitrile
26 in 88% yield (Scheme 4). Addition of isobutylmagne-
sium chloride to nitrile 26 in refluxing benzene gave
enone 27 in 88% yield.26 Hydrogenation of 27 in 50/1
mixture of dioxane and acetic acid provided a 1/1 mixture
of C-20 epimers 28 in 90% yield. The lack of selectivity
in the alkene hydrogenation is presumably due to a small
energy difference between rotamers around the C-17/C-
20 bond which reveals both alkene faces for reduction.
F igu r e 1.
As we expected, treatment of a mixture of diketones 29a /
29b with aqueous sodium hydroxide in methanol at room
temperature provided the desired aldol product 30 along
with unreacted 29b.29 The reaction was quantitative
based on unreacted starting material. The stereochem-
istry of aldol product 30 was confirmed by a combination
(15) Magid, R. M. Tetrahedron 1979, 36, 1901.
(16) Kelly, R. W.; Sykes, P. J . J . Chem. Soc. (C) 1968, 416.
(17) Takano, S.; Hatakeyama, M.; Ogasawasa, H. J . Chem Soc.,
Chem. Commun. 1977, 68.
(18) Corey, E. J .; Erickson, B. W. J . Org. Chem. 1971, 36, 3553.
(19) Rama Rao, A. V.; Venkatswamy, G.; J aveed, S. M.; Deshpande,
V. H.; Rao, B. R. J . Org. Chem. 1983, 48, 1552.
(20) Chattopadhyaya, J . B.; Rama Rao, A. V. Tetrahedron Lett. 1973,
14, 3735.
1
of H NMR DQCOSY and NOESY experiments (Figure
2, Table 1).
(21) Lipshutz. B. H.; Moretti, R.; Crow, R. Tetrahedron Lett. 1989,
30, 15.
(22) Smith, R. A.; Hannah, D. J . Synth. Commun. 1979, 9, 301.
(23) Askin, D.; Angst, D.; Danishefsky, S. J . Org. Chem. 1987, 52,
622.
(24) J oannou, G. E.; Reeder, A. Y. Steroids 1996, 61, 82.
(25) J oannou, G. E.; Reeder, A. Y. Steroids 1996, 61, 74.
(26) Canonne, P.; Foscolos, S.; Lemay, F. Tetrahedron Lett. 1980, 155.
Even though we had successfully synthesized the fully
functionalized C/D/E ring system of the xestobergsterol
(27) Corey, E. J .; Bock, M. G. Tetrahedron Lett. 1975, 2643.
(28) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 40, 2554.
(29) Heathcock, C. H. in Comprehensive Organic Synthesis; Trost,
B. M., kEd.; Pergamon: Oxford, 1991; Vol. 2, p 133.

2478 J . Org. Chem., Vol. 64, No. 7, 1999
Krafft et al.
F igu r e 2.
Ta ble 1. 1H NMR NOE En h a n cem en ts for 30
irradiation
NOE (%)
16R-H
17R-H, 24-H (6)
12R-H (4)
20â-H
14â-H
17R-H
14â-H (5)
22â-H (3)
18-H (2)
8â-H (4)
16R-H, 12R-H, 21-H (3)
steroids, the lack of stereocontrol during the hydrogena-
tion step was not satisfying. Our approach was therefore
modified in order to introduce the C-20 stereogenic center
with total stereocontrol. Wittig olefination of hydroxy
ketone 25 provided hydroxy alkene 31 in 73% yield
(Scheme 5). Hydroboration with dicyclohexyl borane in
THF at 0 °C followed by borane oxidation provided only
one isomer, diol 32 (79% yield).30-33
F igu r e 3. Side-chain conformers of alkene 31.
The stereochemical outcome of the reaction can be
explained in terms of steric hindrance to approach of the
borane. MM2 calculations [Molecular Mechanics, Version
4.0, CAChe system, Oxford Molecular group] indicated
the presence of two favored conformers whose energy
differs by 0.4 kcal (Figure 3). In A, the si face is blocked
by C-18 and C-12. However, the re face is relatively
unhindered toward approach of the bulky borane. In
conformer B, the re face is blocked by C-18, and approach
of the reagent to the si face will be hindered by C-16.
Thus, the observed stereochemical outcome for the
conversion of 31 to 32 is most readily rationalized by the
approach of the borane to the re face of conformer A.
Selective tosylation of the primary alcohol in pyridine
(90% yield) followed by displacement with potassium
cyanide in DMSO provided the desired nitrile 34 in 84%
yield.34
Sch em e 5
Addition of isobutylmagnesium chloride in refluxing
benzene provided ketone 35 after imine hydrolysis on
silica gel (86%). PCC oxidation provided diketone 29a
which was cyclized with concomitant C-14 epimerization
to hydroxy ketone 30 in quantitative yield. The C-20
stereocenter, derived from the hydroboration, was there-
fore confirmed by successful cyclization. We therefore
have effectively synthesized the C/D/E ring system of the
xestobergsterol steroids with complete stereocontrol.
With the C/D/E rings in place, we turned our attention
to incorporating the alcohols at C-3, C-6, and C-7 in
xestobergsterol-A by transformation of testosterone, 4.
Deconjugative ketalization of testosterone,35 gave the
corresponding â,γ-deconjugated ketal alcohol 36 in 85%
yield (Scheme 6). Subsequent protection using KH/MeI
provided methyl ether 37 in 95% yield. Allylic oxidation
(34) Konno, K.; Ojima, K.; Hayashi, T.; Takayama, H. Chem. Pharm.
Bull. 1992, 40, 1120.
(35) Nitz, T. J .; Paquette, L. A. Tetrahedron Lett. 1984, 25, 3047.
Choe, Y. S.; Katzenellenbogen, J . A. Steroids 1995, 60, 414. Corey, E.
J .; Ohno, M.; Mitra, R. B.; Vatakencherry, P. A. J . Am. Chem. Soc.
1964, 86, 478.
(30) Midland, M. M.; Kwon, Y. C. J . Am. Chem. Soc. 1983, 105, 5725.
(31) Midland, M. M.; Kwon, Y. C. Tetrahedron Lett. 1984, 25, 5981.
(32) Midland, M. M.; Kwon, Y. C. Tetrahedron Lett. 1985, 26, 5017.
(33) Stoilov, I.; Kolaczkowska, E.; Watt, D. S.; St. Pyrek, J .; Carlson,
R. M. K.; Fago, F. J .; Maldowan, J . M. J . Org. Chem. 1993, 58, 3444.

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)
J . Org. Chem., Vol. 64, No. 7, 1999 2479
Sch em e 6
In summary, we have now successfully, in separate
compounds, synthesized both ends of the xestobergsterol
skeleton. By taking advantage of the rigidity of the
steroid skeleton we were able to carry out the aldol ring
closure5 and C-14 epimerization stereoselectively. Fur-
ther studies toward achieving the total synthesis of 1 are
currently in progress.
Exp er im en ta l Section
Tetrahydrofuran (THF) and diethyl ether (Et2O) were
distilled from potassium-benzophenone ketyl prior to each
use. Methylene chloride (CH2Cl2) and pyridine were distilled
from calcium hydride. Hexane, chloroform (CHCl3), methanol
(MeOH), and ethyl acetate (EtOAc) were distilled prior to use.
Toluene was distilled from sodium metal prior to use. All
reactions were performed under an atmosphere of nitrogen.
Chromatography refers to flash chromatography as reported
by Still.39 All protons were assigned using 1H NMR decoupling
and NOE experiments.
of 37 with Collins reagent,36 followed by lithium-am-
monia reduction of the resulting enone 38 resulted in the
formation of ketone 39 in 76% overall yield. Ketone 39
was then converted into the corresponding trimethylsilyl
enol ether 40 by reaction with LDA and TMSCl. Hy-
droboration of 40 with BH3-THF complex gave the
desired diol 41 in 65% yield from 39. The stereochemical
outcome of the enol ether hydroboration can be explained
by approach of the reagent from the R-face via a boatlike
conformation of the transition state to avoid 1,3 diaxial
interactions between the incoming boron reagent and the
C-10 methyl group. This explanation is in accord with
the stereochemical outcome of enolate alkylations in six-
membered rings.37 The stereochemistry was confirmed
by 1H NOE experiments on mono benzoate 42, which was
obtained by selective benzylation of 41 with benzyl
chloride in the presence of triethylamine.
3â-(Meth oxym eth oxy)-5r-a n d r ost-15-en -17-on e (10). To
i
a solution of Pr2NH (5 mL, 36 mmol) in THF (84 mL) cooled
to -78 °C was added a solution of BuLi in hexanes (22.8 mL,
36 mmol). The mixture was stirred at -78 °C for 15 min. A
solution of 3â-(methoxymethoxy)-5R-androstan-17-one (6 g, 18
mmol) in THF (18 mL) was added dropwise over a 30-min
period, and the reaction mixture was stirred at -78 °C for an
additional 15 min. Then, NEt 3 (7.5 mL, 54 mmol) and TMSCl
(3.4 mL, 24.3 mmol) were added. The mixture was warmed to
rt and stirred for an additional 25 min and then quenched with
saturated NaHCO3. The aqueous layer was extracted twice
with EtOAc, and the combined organic layers were dried over
MgSO4 and condensed under vacuum. The crude enol ether
was then dissolved in CH2Cl2 (15 mL) and CH3CN (75 mL).
Palladium acetate (4.4 g, 19 mmol) was added in one portion.
The reaction mixture was stirred for 2 h at rt. It was filtered
twice through silica gel pads (3/1 hexane EtOAc). Purification
of the residue by flash chromatography on silica gel (3/1 hexane
1
EtOAc) gave 10 as white needles (5.72 g, 96%). 500-MHz H
With the B ring completely functionalized, modification
of the A ring was straightforward. Deprotection of ketal
41 with acetone and a catalytic amount of p-TsOH
provided the keto diol 43 which was reduced using
L-Selectride38 to give triol 44. The relative stereochem-
NMR: δ 0.80 (m, 1H, H-9R), 0.89 (s, 3H, H-19), 1.00 (ddd, J )
3.9, 13.8, 13.8, 1H, H-1R), 1.06 (m, 3H, H-18), 1.10 (m, 1H,
H-7R), 1.18 (m, 1H, H-5R), 1.32 (m, 1H, H-6â), 1.35 (m, 2H,
H-4â, H-6R), 1.47 (m, 1H, H-2â), 1.49 (m, 1H, H-11â), 1.50 (m,
1H, H-12R), 1.65 (m, 1H, H-4R), 1.70 (m, 1H, H-11R), 1.71 (m,
1H, H-1â), 1.78 (m, 1H, H-8â), 1.85 (m, 1H, H-12â), 1.86 (m,
1H, H-2R), 1.99 (dddd, J ) 12.8, 3.9, 3.9, 3.9, 1H, H-7â), 2.27
(ddd, J ) 11.4, 2.3, 2.3, 1H, H-14R), 3.37 (s, 3H, CH3O), 3.51
(dddd, J ) 5, 5, 11.2, 11.2, 1H, H-3R), 4.67 (bs, 2H, OCH2O),
6.01 (dd, J ) 3, 6, 1H, H-16), 7.50 (ddd, J ) 1, 3, 6, 1H, H-15).
75-MHz 13C NMR: δ 12.06, 20.03, 20.45, 28.18, 28.48, 29.09,
30.67, 32.31, 35.11, 35.92, 36.63, 45.10, 51.03, 55.01, 55.80,
56.92, 76.15, 94.70, 131.95, 158.61, 213.46. IR (cm-1): 2909,
1696. Mass spectrum m/e (PCI:isobutane): 333 (M+ + 1, 100).
Anal. Calcd for C21H32O3‚0.4H2O: C, 74.26; H, 9.61. Found:
C, 74.27; H, 9.58. Mp (°C): 56-58. [R]25D -52 (c ) 17.4, CHCl3).
3â-(Meth oxym eth oxy)-5r-a n d r osta n -17-on e. To a solu-
tion of 3â-hydroxy-5R-androstan-17-one (20 g, 66.8 mmol) and
iPr2NEt (23.2 mL, 133.6 mmol) in CH2Cl2 (330 mL) cooled to
0 °C was added methoxymethyl chloride (7.6 mL, 100.2 mmol).
The solution was kept at 0 °C and stirred for 1 h. It was then
allowed to warm to rt and stir overnight. The mixture was
1
istry of 44 was determined by difference H NOE experi-
ments and coupling constants. The coupling constants
of equatorial H3 (dddd, J ) 2.9, 2.9, 2.9, 2.9 Hz), axial
H6 (dd, J ) 11.2, 8.6 Hz), and axial H7 (dd, J ) 9.9, 8.6
Hz) determined the R-(C3 and C6) and â-(C7) oriented
hydroxyl groups. The NOE between H3 and both R-H4
and â-H4 also supports the axial hydroxyl group at the
C-3 position. The NOE between H6 and â-H4, H8 and
19-CH3, confirmed the C6 configuration. The NOE ob-
served between H7 and H5, H9 and H14, indicated a
â-hydroxyl group at the C7 position.
(36) Kato, M.; Kurihara, H.; Yoshikoshi, A. J . Chem. Soc., Perkin
Trans. 1 1979, 2740.
(37) Evans, D. in Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic: Orlando, 1984; Chapter 1, Vol. 3.
(38) Brown, H. C.; Krishnamurthy, S. J . Am. Chem. Soc. 1972, 94,
7159.
(39) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923

2480 J . Org. Chem., Vol. 64, No. 7, 1999
Krafft et al.
then diluted with CH2Cl2 and washed with water, 10% HCl,
saturated NaHCO3, and brine. The organic layer was then
dried over anhydrous MgSO4 and condensed to give a white
solid. Purification by flash chromatography on silica gel (3/1
hexane/EtOAc) gave 3â-(methoxymethoxy)-5R-androstan-17-
1.96-2.03 (m, 1H), 2.00 (s, 3H), 2.72-2.89 (m, 2H), 2.92-3.08
(m, 2H), 3.53 (dddd, J ) 5.5, 5.5, 10.5, 10.5, 1H), 5.80 (bs, 1H),
6.11 (d, J ) 5.5, 1H). 75-MHz 13C NMR: δ 0.03 (3C), 12.09,
18.13, 21.13, 26.21, 28.37, 31.62, 31.86, 33.25, 33.54, 35.55,
36.75, 38.36, 45.09, 53.87, 54.58, 57.69, 71.79, 91.73, 134.86.
IR (cm-1): 2934, 2859, 1453. Mass spectrum m/e (PCI:
isobutane): 496 (M+ + 1), 477 (M+ - 18), 361 (M+ - 134, 100).
Anal. Calcd for C27H46O2SiS2: C, 65.53; H, 9.37. Found: C,
1
one as white needles (22.1 g, 99%). 500-MHz H NMR: δ 0.69
(dd, J ) 3.9, 11.4, 11.4, 1H, H-9R), 0.84 (s, 3H, H-19), 0.86 (s,
3H, H-18), 0.94 (m, 1H, H-1R), 0.98 (m, 1H, H-7R), 1.12 (m,
1H, H-5R), 1.20-1.38 (m, 3H, H-6R, H-6â, H-12), 1.26 (m, 1H,
H-14R), 1.32 (m, 1H, H-11â), 1.34 (m, 1H, H-4â), 1.45 (m, 1H,
H-2â), 1.49 (m, 1H, H-15R), 1.55 (m, 1H, H-8â), 1.62-1.69 (m,
1H, H-12), 1.64 (m, 1H, H-4R), 1.65 (m, 1H, H-11R), 1.74 (ddd,
J ) 13.3, 3.4, 3.4, 1H, H-1â), 1.80 (m, 1H, H-7â), 1.87 (m, 1H,
H-2R), 1.92 (m, 1H, H-15â), 2.05 (ddd, J ) 9.1, 9.1, 19.1, 1H,
H-16R), 2.43 (ddd, J ) 1, 9.1, 19.1, 1H, H-16â), 3.50 (dddd, J
) 4.9, 4.9, 11.1, 11.1, 1H, H-3R), 3.36 (s, 3H, CH3O), 4.67 (bs,
2H, OCH2O). 75-MHz 13C NMR: δ 12.00, 13.60, 20.29, 21.58,
28.33, 28.51, 30.77, 31.46, 34.98, 35.13, 35.68, 36.87, 44.86,
47.66, 51.41, 54.49, 55.02, 76.21, 94.68, 221.50. IR (cm-1):
65.64; H, 9.31. Mp (°C): 154-155. [R]25 -74 (c ) 1, CHCl3).
D
20,20-(Tr im eth ylen ed ith io)-5r-p r egn -16-en e-3â,15â-d i-
ol (21). To a solution of 19 (1.46 g, 2.95 mmol) in THF (80
mL) was added an aqueous solution of 0.45% H2SO4 (70 mL).
The mixture was stirred at rt for 6 days. Concentrated sulfuric
acid (0.16 mL) was then added dropwise and the mixture was
stirred at rt for another 3 days. After neutralizing with 2, N
NaOH, most of the solvent was removed under vacuum. The
residue was dissolved in CHCl3, and the aqueous layer was
extracted several times. The combined organic layers were
dried over MgSO4 and condensed under vacuum. Purification
of the residue by flash chromatography on silica gel (1/1 hexane
EtOAc) afforded 21 as a white solid (1 g, 80%). 500-MHz 1H
NMR: δ 0.77 (ddd, J ) 4.8, 11.4, 11.4, 1H, H-9R), 0.88 (s, 3H,
H-19), 0.98 (ddd, J ) 3.8, 13.4, 13.4, 1H, H-1R), 1.06 (dddd, J
) 5.7, 11.8, 11.8, 11.8, 1H, H-7R), 1.15 (m, 1H, H-5R), 1.25-
1.36 (m, 2H, H-6R, H-6â), 1.31 (m, 1H, H-4â), 1.37 (dd, J ) 5,
11.4, 1H, H-14R), 1.41 (m, 1H, H-11â), 1.42 (s, 3H, H-18), 1.43
(m, 1H, H-2â), 1.56 (m, 1H, H-12R), 1.58 (m, 1H, H-4R), 1.60
(m, 1H, H-11R), 1.72 (ddd, J ) 3.8, 13.4, 13.4, 1H, H-1â), 1.79
(s, 3H, H-21), 1.83 (m, 1H, H-2R), 1.86 (m, 1H, H-8â), 1.96
(dddd, J ) 3.7, 3.7, 3.7, 11.8, 1H, H-7â), 1.97 (m, 2H, SCH2CH2-
CH2S), 2.16 (m, 1H, H-12â), 2.78-2.90 (m, 4H, SCH2-
CH2CH2S), 3.60 (dddd, J ) 4.8, 4.8, 11.1, 11.1, 1H, H-3R), 4.48
(dd, J ) 3.5, 5, 1H, H-15R), 6.26 (d, J ) 3.5, 1H, H-16). 75-
MHz 13C NMR: δ 12.00, 20.72, 24.50, 24.66, 27.64, 28.27,
28.33, 29.58, 30.60, 31.01, 31.20, 35.51, 36.55, 36.65, 37.87,
44.98, 48.66, 50.21, 54.66, 60.59, 71.05, 72.03, 131.79, 161.82.
IR (cm-1): 3455, 2934, 2860. Mass spectrum m/e (PCI:
isobutane): 405 (M+ - 90, 100), 315 (M+ - 180). Mp (°C):
2925, 1721. Mass spectrum m/e (PCI: isobutane): 335 (M+
1), 303 (M+ - 31), 273 (M+ - 61, 100). Anal. Calcd for
+
C
21H34O3: C, 75.41; H, 10.25. Found: C, 75.25, H, 10.15. Mp
(°C): 95-96. [R]25 +46 (c ) 29.4, CHCl3).
D
3â-((Tr im eth ylsilyl)oxy)-5r-a n d r ost-15-en -17-on e (18).
i
To a solution of Pr2NH (2.95 mL, 21 mmol) in THF (29 mL)
cooled to -78 °C was added a solution of BuLi in hexanes (13.2
mL, 21 mmol). The mixture was stirred at -78 °C for 15 min.
A solution of 3â-hydroxy-5R-androstan-17-one (2.1 g, 7 mmol)
in THF (7 mL) was added dropwise over a 30-min period, and
the reaction mixture was stirred at -78 °C for an additional
15 min. Then, NEt3 (3.9 mL, 28 mmol) and TMSCl (2.7 mL,
19 mmol) were added. The mixture was warmed to rt, stirred
for an additional 25 min, and then quenched with saturated
NaHCO3. The aqueous layer was extracted twice with EtOAc,
and the combined organic layers were dried over MgSO4 and
condensed under vacuum. The crude enol ether was then
dissolved in CH2Cl2 (30 mL) and CH3CN (10 mL). Palladium
acetate (1.73 g, 7.4 mmol) was added in one portion. The
reaction mixture was stirred for 3 h at 35-40 °C (water bath).
It was filtered twice through silica gel pads (3/1 hexane
EtOAc). Purification of the residue by flash chromatography
on silica gel (3/1 hexane EtOAc) gave 18 as white needles (2.39
g, 95%). 500-MHz 1H NMR: δ 0.11 (s, 9H, (CH3)3SiO), 0.77
(m, 1H, H-9R), 0.86 (s, 3H, H-19), 0.97 (ddd, J ) 4.1, 13.1,
13.1, 1H, H-1R), 1.05 (s, 3H, H-18), 1.08 (m, 1H, H-7R), 1.15
(m, 1H, H-5R), 1.32 (m, 1H, H-6â), 1.36 (m, 2H, H-6R, H-4â),
1.47 (m, 2H, H-4R, H-2â), 1.48 (m, 1H, H-11â), 1.49 (m, 1H,
H-12R), 1.67 (m, 1H, H-1â), 1.70 (m, 1H, H-2R), 1.71 (m, 1H,
H-11R), 1.77 (dddd, J ) 3.9, 11.5, 11.5, 11.5, 1H, H-8â), 1.85
(m, 1H, H-12â), 1.97 (dddd, J ) 3.7, 12.6, 12.6, 12.6, 1H, H-7â),
2.26 (ddd, J ) 11.5, 3, 3, 1H, H-14R), 3.55 (dddd, J ) 4.8, 4.8,
11, 11, 1H, H-3R), 6.00 (dd, J ) 3, 6, 1H, H-16), 7.50 (dd, J )
1, 6, 1H, H-15). 75-MHz 13C NMR: δ 0.01 (3C), 12.13, 20.01,
20.52, 28.09, 29.00, 30.66, 31.57, 32.20, 35.73, 36.70, 38.28,
45.15, 51.05, 55.72, 56.87, 71.57, 131.77, 158.82, 213.63. IR
(cm-1): 2935, 2862, 1703. Mass spectrum m/e (PCI:isobu-
tane): 361 (M+ + 1, 100). Anal. Calcd for C22H36O2Si: C, 73.28;
165-168. [R]25 -72 (c ) 1, CHCl3).
D
3â,15â-Dih yd r oxy-5r-p r egn -16-en -20-on e (22). To a solu-
tion of 21 (2.04 g, 4.83 mmol) in MeOH (63 mL) and THF (16
mL) was added rapidly a solution of thallium nitrate trihydrate
(9.67 mmol, 4.29 g) in MeOH (16 mL). The reaction mixture
was stirred for 10 min at rt, diluted with water, and extracted
with CHCl3. After concentration in vacuo, the residue was
subjected to flash chromatography (silica gel; 9/1 CH2Cl2/
1
acetone) to give 22 (990 mg, 62%). 500-MHz H NMR: δ 0.79
(ddd, J ) 4.5, 10.2, 12.4, 1H, H-9R), 0.88 (s, 3H, H-19), 0.99
(ddd, J ) 3.8, 13.4, 13.4, 1H, H-1R), 1.11 (dddd, J ) 5.7, 11.8,
11.8, 11.8, 1H, H-7R), 1.16 (m, 1H, H-5R), 1.23 (m, 1H, H-12R),
1.23 (s, 3H, H-18), 1.28 (dd, J ) 5.4, 12.1, 1H, H-14R), 1.3-
1.4 (m, 1H, H-6R), 1.32 (m, 1H, H-4â), 1.38 (m, 1H, H-6â), 1.42
(m, 1H, H-2â), 1.46 (m, 1H, H-11â), 1.59 (m, 1H, H-4R), 1.61
(m, 1H, H-11R), 1.72 (ddd, J ) 13.4, 3.5, 3.5, 1H, H-1â), 1.82
(m, 1H, H-2R), 1.84 (m, 1H, H-8â), 1.96 (dddd, J ) 11.8, 3.3,
3.3, 3.3, 1H, H-7â), 2.26 (ddd, J ) 2.5, 5, 12.7, 1H, H-12â),
2.31 (s, 3H, H-21), 3.6 (dddd, J ) 4.8, 4.8, 11.1, 11.1, 1H, H-3R),
4.65 (dd, J ) 2.9, 5.4, 1H, H-15R), 6.65 (d, J ) 2.9, 1H, H-16).
δ 75-MHz 13C NMR (MeOH): δ 12.65, 21.91, 22.47, 27.57,
29.78, 32.13, 32.22, 36.27, 37.00, 38.00, 38.90, 46.64, 48.09,
56.87, 60.68, 71.90, 73.43, 145.33, 158.47, 200.48. IR (cm-1):
3439, 2935, 1671.. Mass spectrum m/e (PCI:isobutane): 315
(M+ - 17), 299 (M+ - 34, 100). Anal. Calcd for C21H32O3‚0.7
H2O: C, 73.09; H, 9.54. Found: C, 73.09; H, 9.75. Mp (°C):
H, 10.06. Found: C, 73.43; H, 10.00. Mp (°C): 107-108. [R]25
-51 (c ) 1, CHCl3).
D
3â-((Tr im et h ylsilyl)oxy)-20,20-(t r im et h ylen ed it h io)-
5r-p r egn -15-en -17â-ol (19). To a solution of 2-methyl-1,3-
dithiane (1.72 mL, 15.26 mmol) in THF (30 mL) cooled to -20
°C was added a solution of BuLi in hexanes (9.82 mL, 15.26
mmol). The mixture was stirred at -20 °C for 1.5 h. A solution
of 18 (5.39 g, 14.97 mmol) in THF (35 mL) was then added
dropwise, and the reaction was allowed to warm to rt and stir
for 20 h. The mixture was then quenched with a saturated
solution of NH4Cl. The aqueous layer was extracted with
EtOAc, and the combined organic layers were dried over
MgSO4 and condensed under vacuum. Purification of the
residue by flash chromatography on silica gel (12/1 hexane
EtOAc) gave 19 as a white solid (7.03 g, 95%). 500-MHz 1H
NMR: δ 0.10 (s, 9H), 0.63-0.75 (m, 1H), 0.81 (s, 3H), 0.86-
1.00 (m, 2H), 1.01 (s, 3H), 1.05-1.12 (m, 1H), 1.22-1.50 (m,
7H), 1.52 (bs, 1H), 1.58-1.70 (m, 4H), 1.83-1.94 (m, 3H),
181-183. [R]25 -29 (c ) 1, MeOH).
D
3â-[(ter t-Bu tyldim eth ylsilyl)oxy]-15â-h ydr oxy-5r-pr egn -
16-en -20-on e (24). To a solution of 22 (300 mg, 0.9 mmol) in
pyridine (5 mL) and CH2Cl2 (5 mL) cooled to -78 °C was added
a solution of tert-butyldimethylsilyl trifluoromethanesulfonate
(0.9 mmol, 0.23 mL) in CH2Cl2 (2 mL) dropwise. Additional
TBDMSOTf/CH2Cl2 solution was then added (0.1 equiv at a
time) until the reaction was complete. It was then quenched
at -78 °C by addition of a saturated NH4Cl solution. The
aqueous layer was extracted with EtOAc, and the combined
organic layers were dried over MgSO4 and condensed under

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)
J . Org. Chem., Vol. 64, No. 7, 1999 2481
vacuum. Purification of the residue by flash chromatography
H-8â), 1.78 (m, 2H, H-16â, H-12â), 1.89 (dddd, J ) 13.4, 3.2,
3.2, 3.2, 1H, H-7â), 2.09 (s, 3H, H-21), 2.13 (dd, J ) 9.6, 9.6,
1H, H-17R), 2.30 (ddd, J ) 16, 9.6, 9.6, 1H, H-16R), 3.55 (dddd,
J ) 5.1, 5.1, 10.8, 10.8, 1H, H-3R), 4.32 (ddd, J ) 2.5, 5.7, 9.6,
1H, H-15R), 5.18 (s, 1H, H-22). 75-MHz 13C NMR: δ -4.80
(2C), 12.14, 15.34, 18.08, 20.87, 22.49, 25.78 (3C), 28.33, 31.47,
31.73, 35.57, 37.00, 37.84, 38.41, 39.86, 44.37, 45.00, 54.73,
58.37, 60.78, 70.26, 71.98, 96.01, 117.54, 164.74. IR (cm-1):
3494, 2932, 2856, 1618. Mass spectrum m/e (PCI:isobutane):
472 (M+), 133 (M+ - 339, 100). Anal. Calcd for C29H49O2NSi:
C, 73.83; H, 10.47. Found: C, 73.96; H, 10.55. Mp (°C): 193-
on silica gel (3/1 hexane EtOAc) gave 24 as a white solid (363
1
mg, 90%). 500-MHz H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.76
(ddd, J ) 4.5, 10.2, 12.1, 1H, H-9R), 0.88 (s, 9H, (CH3)3CSiO),
0.89 (s, 3H, H-19), 0.95 (ddd, J ) 4.5, 13.2, 13.2, 1H, H-1R),
1.09 (dddd, J ) 5.7, 11.8, 11.8, 11.8, 1H, H-7R), 1.12 (m, 1H,
H-5R), 1.22 (s, 3H, H-18), 1.22 (m, 1H, H-12R), 1.27 (dd, J )
5.4, 12.1, 1H, H-14R), 1.3-1.4 (m, 1H, H-6R), 1.34 (m, 1H,
H-6â), 1.36 (m, 1H, H-4â), 1.44 (m, 1H, H-11â), 1.45 (m, 2H,
H-2â, H-4R), 1.60 (m, 1H, H-11R), 1.67 (m, 1H, H-1â), 1.69
(m, 1H, H-2R), 1.82 (dddd, J ) 3.8, 12.1, 12.1, 12.1, 1H, H-8â),
1.93 (dddd, J ) 12.1, 3.8, 3.8, 3.8, 1H, H-7â), 2.25 (ddd, J )
2.4, 4.6, 12.8, 1H, H-12â), 2.31 (s, 3H, H-21), 3.55 (dddd, J )
5, 5, 10.9, 10.9, 1H, H-3R), 4.65 (bs, 1H, H-15R), 6.65 (d, J )
2.5, 1H, H-16). 75-MHz 13C NMR: δ -4.85 (2C), 12.07, 18.04,
20.55, 22.61, 25.74 (3C), 27.43, 28.34, 30.70, 31.08, 31.69,
34.80, 35.71, 36.73, 38.44, 45.26, 46.82, 55.40, 59.13, 72.01,
73.29, 141.92, 158.04, 197.87. IR (cm-1): 2931, 1671. Mass
spectrum m/e (PCI:isobutane): 448 (M+ + 1), 432 (M+ - 15,
100), 299 (M+ - 148). Anal. Calcd for C27H46O3Si: C, 72.59;
194. [R]25 -7 (c ) 1, CHCl3).
D
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-15â-h yd r oxy-5r-ch ol-
est-20-en -23-on e (27). To a solution of 26 (375 mg, 0.8 mmol)
in benzene (7 mL) at rt was added a 2 M solution of
isobutylmagnesium bromide in ether (2 mL). The reaction
mixture was then brought to reflux and stirred for 4 h. After
cooling, it was quenched with a saturated NH4Cl solution. The
aqueous layer was extracted with EtOAc, and the combined
organic layers were dried over MgSO4 and condensed under
vacuum. Purification of the residue by flash chromatography
on silica gel (3/1 hexane EtOAc) gave 27 as a white solid (373
H, 10.38. Found: C, 72.68; H, 10.30. Mp (°C): 178-179. [R]25
-12 (c ) 1, CHCl3).
D
1
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-15â-h yd r oxy-5r-p r eg-
n a n -20-on e (25). A solution of 24 (0.9 g, 2.02 mmol) in EtOH
(50 mL) was added to a flask containing 0.3 g 5% Rh/Alumina.
The reaction vessel was then fitted with a balloon filled with
hydrogen, and the mixture was stirred for 3 h at rt. The
resulting mixture was then filtered through a pad of Celite
and concentrated in vacuo, and the residue was subjected to
column chromatography (silica gel) using a 3/1 mixture of
hexane/EtOAc as the eluent to give 25 as white needles (0.88
g, 97%). 500-MHz 1H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.73
(ddd, J ) 3.8, 11.5, 11.5, 1H, H-9R), 0.84 (s, 3H, H-19), 0.88
(s, 12H, (CH3)3CSiO), H-18), 0.96 (ddd, J ) 4.2, 12.7, 12.7, 1H,
H-1R), 1.01 (dddd, J ) 5.4, 11.5, 11.5, 11.5, 1H, H-7R), 1.02
(dd, J ) 5.7, 11.5, 1H, H-14R), 1.10 (m, 1H, H-5R), 1.3-1.4
(m, 1H, H-6R), 1.33 (m, 1H, H-6â), 1.34 (m, 2H, H-4â, H-11â),
1.37 (m, 1H, H-12R), 1.45 (m, 1H, H-4R), 1.45 (m, 1H, H-2â),
1.62 (m, 1H, H-11R), 1.68 (m, 1H, H-1â), 1.69 (m, 1H, H-2R),
1.74 (dddd, J ) 3.8, 11.5, 11.5, 11.5, 1H, H-8â), 1.94 (dddd, J
) 11.5, 3.7, 3.7, 3.7, 1H, H-7â), 1.99 (ddd, J ) 2.4, 4.6, 12.8,
1H, H-12â), 2.13 (s, 3H, H-21), 2,0.19 (ddd, J ) 9.4, 9.6, 15,
1H, H-16), 2.23 (ddd, J ) 2.5, 9.4, 15, 1H, H-16′), 2.46 (dd, J
) 9.4, 9.4, 1H, H-17R), 3.56 (dddd, J ) 4.6, 4.6, 10.8, 10.8,
1H, H-3R), 4.29 (ddd, J ) 2.5, 5.7, 9.6, 1H, H-15R). 75-MHz
13C NMR: δ -4.82 (2C), 12.11, 15.79, 18.04, 20.94, 25.76 (3C),
28.35, 31.20, 31.46, 35.55, 35.66, 37.04, 38.43, 40.46, 43.72,
45.02, 54.64, 60.95, 63.88, 70.51, 72.00, 208.78. IR (cm-1):
2931, 2856, 1701. Mass spectrum m/e (PCI: isobutane): 431
(M+ - 17), 299 (M+ - 150, 100). Anal. Calcd for C27H48O3Si‚
0.2H2O: C, 71.69; H, 10.78. Found: C, 71.68; H, 10.79. Mp )
mg, 88%). 500-MHz H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.72
(ddd, J ) 4.3, 12.4, 12.4, 1H, H-9R), 0.82 (s, 3H, H-18), 0.84
(s, 3H, H-19), 0.88 (s, 9H, (CH3)3CSiO), 0.92 (d, J ) 7, 6H,
H-26, H-27), 0.95 (m, 1H, H-1R), 1.00 (dd, J ) 5.7, 11, 1H,
H-14R), 1.03 (dddd, J ) 5.4, 11, 11, 11, 1H, H-7R), 1.10 (m,
1H, H-5R), 1.17 (ddd, J ) 3.4, 11.9, 11.9, 1H, H-12R), 1.28 (m,
1H, H-11â), 1.3-1.4 (m, 1H, H-6R), 1.31 (m, 1H, H-6â), 1.34
(m, 1H, H-4â), 1.45 (m, 2H, H-4R, H-2â), 1.56 (m, 1H, H-11R),
1.68 (m, 1H, H-1â), 1.69 (m, 1H, H-2R), 1.73 (m, 1H, H-8â),
1.76 (ddd, J ) 11.9, 3.1, 3.1, 1H, H-12â), 1.89 (ddd, J ) 15.8,
8.7, 2.5, 1H, H-16â), 1.91 (dddd, J ) 11, 3.2, 3.2, 3.2, 1H, H-7â),
2.09 (dd, J ) 8.7, 8.7, 1H, H-17R), 2.13 (m, 1H, H-25), 2.15 (s,
3H, H-21), 2.26 (ddd, J ) 15.8, 8.7, 8.7, 1H, H-16R), 2.30 (d, J
) 7.1, 2H, H-24), 3.55 (dddd, J ) 4.8, 4.8, 10.9, 10.9, 1H, H-3R),
4.33 (ddd, J ) 2.5, 5.7, 8.7, 1H, H-15R), 6.09 (s, 1H, H-22).
75-MHz 13C NMR: δ -4.82 (2C), 12.13, 15.42, 18.04, 20.89,
21.04, 22.47, 25.15, 25.76 (3C), 28.37, 31.34, 31.49, 31.73,
35.55, 37.00, 37.74, 38.43, 40.00, 44.24, 45.00, 53.72, 54.84,
60.42, 60.83, 70.53, 71.98, 124.18, 157.15, 201.63. IR (cm-1):
3475, 2932, 1677, 1602. Mass spectrum m/e (PCI:isobutane):
513 (M+ - 18), 133 (M+ - 398, 100),. Anal. Calcd for C33H58O3-
Si: C, 74.66; H, 11.01. Found: C, 74.73; H, 11.09. Mp (°C):
164-165. [R]25 -4 (c ) 1, CHCl3).
D
(20R)-3â-[(ter t-Bu t yld im et h ylsilyl)oxy]-15â-h yd r oxy-
5r-ch olesta n -23-on e a n d (20S)-3â-[(ter t-Bu tyld im eth yl-
silyl)oxy]-15â-h yd r oxy-5r-ch olesta n -23-on e (28). A solu-
tion of 3â-[(tert-butyldimethylsilyl)oxy]-15â-hydroxy-5R-cholest-
20-en-23-one (212 mg, 0.4 mmol) in 50/1 dioxane/AcOH (10
mL) was added to a flask containing PtO2 (21 mg). The reaction
vessel was then fitted with a balloon filled with hydrogen, and
the mixture was stirred for 4.5 h at rt. It was then filtered
through a pad of Celite. After concentration in vacuo, the
residue was subjected to column chromatography (silica gel)
using a 3/1 mixture of hexane/EtOAc as the eluent to give a
1/1 mixture of (20R) and (20S) 28 as a white solid (191 mg,
90%). IR (cm-1): 2933, 2857, 1707. Mass spectrum m/e (PCI:
isobutane): 515 (M+ - 18), 383 (M+ - 150), 133 (M+ - 400,
100). Anal. Calcd for C33H60O3Si: C, 74.37; H, 11.34. Found:
C, 74.16; H, 11.34.
200-201 °C. [R]25 +36 (c ) 1, CHCl3).
D
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-15â-h yd r oxy-24-n or -
5r-ch ol-20-en e-23-n itr ile (26). To a suspension of NaH
(washed 3× with petroleum ether) (83 mg, 3.46 mmol) in THF
(4 mL) at rt was added dropwise diethyl cyanomethylphos-
phonate (0.56 mL, 3.46 mmol). The mixture was stirred at rt
for 1 h. A solution of 25 (575 mg, 1.22 mmol) in THF (4 mL)
was then added dropwise, and the mixture was stirred at rt
for 12 h. Another 3 equiv of ylide was then added, and the
reaction mixture was stirred for an additional 12 h. It was
then quenched with a saturated NH4Cl solution. The aqueous
layer was extracted with EtOAc, and the combined organic
layers were dried over MgSO4 and condensed under vacuum.
Purification of the residue by flash chromatography on silica
gel (12/1 hexane EtOAc) gave 26 as a white solid (506 mg,
88%). 500-MHz 1H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.71 (ddd,
J ) 3.8, 12.1, 12.1, 1H, H-9R), 0.83 (s, 3H, H-18), 0.84 (s, 3H,
H-19), 0.88 (s, 9H, (CH3)3CSiO)), 0.95 (ddd, J ) 3.8, 12.8, 12.8,
1H, H-1R), 0.98 (dd, J ) 5.7, 12.1, 1H, H-14R), 1.01 (dddd, J
) 5.4, 13.4, 13.4, 13.4, 1H, H-7R), 1.10 (m, 1H, H-5R), 1.16
(ddd, J ) 3.8, 12.8, 12.8, 1H, H-12R), 1.29 (m, 1H, H-11â), 1.3-
1.4 (m, 1H, H-6R), 1.31 (m, 1H, H-6â), 1.34 (m, 1H, H-4â), 1.45
(m, 2H, H-4R, H-2â), 1.58 (dddd, J ) 13.4, 3.8, 3.8, 3.8, 1H,
H-11R), 1.68 (m, 1H, H-1â), 1.69 (m, 1H, H-2R), 1.73 (m, 1H,
(20R)-3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-5r-ch olesta n e-
15,23-d ion e (29a ) a n d (20S)-3â-[(ter t-Bu tyld im eth ylsilyl)-
oxy]-5r-ch olesta n e-15,23-d ion e (29b). To a solution of
(20R)-3â-[(tert-butyldimethylsilyl)oxy]-15â-hydroxy-5R-cholestan-
23-one and (20S)-3â-[(tert-butyldimethylsilyl)oxy]-15â-5R-hy-
droxycholestan-23-one (163 mg, 0.3 mmol) in CH2Cl2 (3 mL)
containing some Celite was added PCC (135 mg, 0.6 mmol) in
one portion. The reaction mixture was stirred at rt for 1 h. It
was then filtered through a pad of Celite. After concentration
in vacuo, the residue was subjected to column chromatography
(silica gel) using a 4/1 mixture of hexane/EtOAc as the eluent
to give a 1/1 mixture of 29a and 29b as a white solid (136 mg,
86%). IR (cm-1): 2933, 2857, 1735, 1707. Mass spectrum m/e
(PCI:isobutane): 531 (M+, 100), 399 (M+ - 132), 133 (M+
-

2482 J . Org. Chem., Vol. 64, No. 7, 1999
Krafft et al.
398, 100). Anal. Calcd for C33H58O3Si: C, 74.66; H, 11.01.
Found: C, 74.73; H, 11.09.
was stirred at 0 °C for 24 h. EtOH (3 mL), 6 N NaOH (1 mL),
and 30% H2O2 (2 mL) were then added successively at 0 °C.
The reaction mixture was then warmed to rt and stirred for
24 h. The organic layer was then separated and dried over
MgSO4 and condensed under vacuum. Purification of the
residue by flash chromatography on silica gel (2/1 hexane
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-23â-h yd r oxy-16â,23-
cyclo-5r,14â-ch olesta n -15-on e (30). To a solution of 29a and
29b (120 mg, 0.23 mmol) in ethanol (7 mL) and THF (2 mL)
was added an aqueous solution of NaOH (0.2 mL, 2 N). The
reaction mixture was stirred at rt for 17 h before being
neutralized by 10% HCl. It was then evaporated to dryness,
and the residue was dissolved in CHCl3 and dried. Purification
by flash chromatography (6/1 EtOAc/hexane) afforded 30 (60
mg, >95%) and the recovered unnatural epimer 29b (60 mg).
30: 500-MHz 1H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.74 (s, 3H,
H-19), 0.88 (s, 9H, (CH3)3CSiO), 0.89 (m, 1H, H-9R), 0.91 (m,
1H, H-1R), 0.95 (d, J ) 7, 3H, H-26), 0.96 (d, J ) 7, 3H, H-27),
1.02 (m, 1H, H-12R), 1.09 (d, J ) 6.5, 3H, H-21), 1.12 (s, 3H,
H-18), 1.17 (m, 1H, H-5R), 1.19 (m, 1H, H-11â), 1.2-1.4 (m,
1H, H-6R), 1.21 (m, 1H, H-6â), 1.27 (m, 1H, 22R), 1.32 (m, 1H,
H-4â), 1.39 (m, 2H, H-2â, H-7â), 1.42 (m, 1H, H-12â), 1.47 (m,
1H, H-4R), 1.49 (dd, J ) 6.5, 15, 1H, H-24), 1.57-1.64 (m, 1H,
H-11-R), 1.59 (m, 1H, H-8â), 1.64 (m, 2H, H-1â, H-2R), 1.68
(dd, J ) 6.5, 15, 1H, H-24′), 1.72 (dd, J ) 9.6, 9.6, 1H, H-17R),
1.86 (ddqq, J ) 6.5, 6.5, 7, 7, 1H, H-25), 1.94 (dd, J ) 5.7,
12.8, 1H, H-22â), 2.09 (dd, J ) 2.6, 3.8, 1H, H-14â), 2.27 (dddq,
J ) 5.7, 9.6, 12.2, 6.5, 1H, H-20â), 2.47 (dddd, J ) 4.5, 12.8,
12.8, 12.8, 1H, H-7R), 2.60 (d, J ) 9.6, 1H, H-16R), 3.54 (dddd,
J ) 4.5, 4.5, 11.5, 11.5, 1H, H-3R). 75-MHz 13C NMR: δ -4.84
(2C), 12.01, 18.09, 19.70, 20.29, 21.06, 24.35, 24.46, 24.55,
25.80 (3C), 28.72, 28.85, 31.58, 32.68, 34.22, 35.32, 36.85,
38.06, 38.56, 38.75, 44.03, 47.51, 50.73, 51.92, 56.85, 57.42,
62.92, 72.07, 81.97, 220.66. IR (cm-1): 2931, 2858, 1720. Mass
spectrum m/e (PCI:isobutane): 513 (M+ - 18, 100), 381 (M+
- 150). Anal. Calcd for C33H58O3Si: C, 74.66; H, 11.01.
Found: C, 74.39; H, 10.94. Mp (°C): 55-56. [R]25D -42 (c ) 1,
CHCl3).
1
EtOAc) gave 32 as a white solid (495 mg, 79%). 500-MHz H
NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.68 (ddd, J ) 4.1, 10.5, 12.3,
1H, H-9R), 0.83 (s, 3H, H-19), 0.86 (dd, J ) 5.7, 11.4, 1H,
H-14R), 0.88 (s, 9H, (CH3)3CSiO), 0.95 (s, 3H, H-18), 0.95 (m,
1H, H-1R), 1.00 (dddd, J ) 5.4, 12.7, 12.7, 12.7, 1H, H-7R),
1.04 (d, J ) 7, 3H, H-21), 1.10 (m, 1H, H-5R), 1.13 (m, 1H,
H-12R), 1.16 (dd, J ) 8.7, 10.1, 1H, H-17R), 1.24-1.40 (m, 1H,
H-6R), 1.30 (m, 2H, H-6â, H-11â), 1.34 (m, 1H, H-4â), 1.37 (m,
1H, H-16â), 1.44 (m, 1H, H-4R), 1.45 (m, 1H, H-2â), 1.50 (m,
1H, H-11R), 1.68 (m, 2H, H-1â, H-20), 1.69 (m, 1H, H-2R), 1.71
(m, 1H, H-8â), 1.88 (dddd, J ) 12.7, 3.5, 3.5, 3.5, 1H, H-7â),
1.91 (ddd, J ) 12.8, 3.3, 3.3, 1H, H-12â), 2.37 (ddd, J )
16.5,0.7.9, 7.9, 1H, H-16R), 3.40 (dd, J ) 6.5, 10.5, 1H, H-22),
3.55 (dddd, J ) 4.8, 4.8, 10.8, 10.8, 1H, H-3R), 3.64 (dd, J )
3.2, 10.5, 1H, H-22′), 4.28 (ddd, J ) 2.4, 5.7, 7.9, 1H, H-15R).
75-MHz 13C NMR: δ -4.78 (2C), 12.14, 14.62, 16.64, 18.10,
20.93, 25.80 (3C), 28.46, 31.29, 31.44, 31.81, 35.53, 37.06,
38.17, 38.49, 40.31, 41.17, 42.21, 45.04, 52.66, 54.78, 60.74,
67.83, 70.48, 72.13. IR (cm-1): 2932, 2857. Mass spectrum m/e
(PCI:isobutane): 447 (M+ - 18), 315 (M+ - 150, 100). Anal.
Calcd for C28H52O3Si‚0.8H2O: C, 70.18; H, 11.27. Found: C,
70.17; H, 11.02. Mp (°C): 187-188. [R]25 -12 (c ) 1, CHCl3).
D
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-15â-h yd r oxy-24-n or -
5r-ch ola n e-23-n itr ile (34). To a solution of TsCl (292 mg,
1.55 mmol) in pyridine (3 mL) at 0 °C was added a solution of
32 (480 mg, 1.03 mmol) in pyridine (4 mL). The reaction
mixture was stirred for 24 h at 0 °C. It was then poured into
water and extracted with EtOAc. The combined organic layers
were dried over MgSO4 and condensed under vacuum. The
crude tosylate was obtained (572 mg, 90%) and used without
further purification. It was dissolved in DMSO (3 mL) and
THF (1 mL). KCN (120 mg, 1.85 mmol) was added, and the
reaction mixture was warmed to 60 °C and stirred for 5 h.
After cooling the reaction mixture to rt, it was diluted with a
3/1 mixture of hexane and EtOAc and plugged through a pad
of silica gel. Further purification by flash chromatography
(eluent 3/1 hexane/EtOAc) gave 34 as a white solid (368 mg,
84%). 500-MHz 1H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.69 (ddd,
J ) 3.9, 10.5, 12.4, 1H, H-9R), 0.84 (s, 3H, H-19), 0.88 (s, 9H,
(CH3)3CSiO), 0.92 (dd, J ) 5.7, 11.4, 1H, H-14R), 0.95 (m, 1H,
H-1R), 0.96 (s, 3H, H-18), 1.02 (dddd, J ) 5.4, 12.7, 12.7, 12.7,
1H, H-7R), 1.10 (m, 1H, H-5R), 1.14 (m, 1H, H-12R), 1.16 (d, J
) 7, 3H, H-21), 1.20-1.38 (m, 1H, H-6R), 1.24 (m, 1H, H-17R),
1.31 (m, 2H, H-6â, H-11â), 1.32 (m, 1H, H-16â), 1.34 (m, 1H,
H-4â), 1.44 (m, 1H, H-4R), 1.45 (m, 1H, H-2â), 1.53 (m, 1H,
H-11R), 1.68 (m, 1H, H-1â), 1.69 (m, 1H, H-2R), 1.71 (dddd, J
) 3.6, 11.4, 11.4, 11.4, 1H, H-8â), 1.87 (dddd, J ) 12.7, 3.5,
3.5, 3.5, 1H, H-7â), 1.91 (m, 1H, H-20), 1.92 (m, 1H, H-12â),
2.27 (dd, J ) 6.6, 16.7, 1H, H-22), 2.35 (dd, J ) 3.9, 16.7, 1H,
H-22′), 2.39 (ddd, J ) 16.5, 7.9, 7.9, 1H, H-16R), 3.55 (dddd, J
) 4.8, 4.8, 10.8, 10.8, 1H, H-3R), 4.24 (ddd, J ) 2, 5.7, 7.9, 1H,
H-15R). 75-MHz 13C NMR: δ -4.82 (2C), 12.11, 14.56, 18.07,
19.20, 20.83, 24.64, 25.78 (3C), 28.38, 31.21, 31.34, 31.75,
32.93, 35.49, 37.00, 38.45, 40.40, 40.89, 42.22, 44.96, 54.58,
54.76, 60.77, 70.04, 72.03, 118.80. IR (cm-1): 2932, 2857, 2254.
Mass spectrum m/e (PCI:isobutane): 324 (M+ - 150, 100).
Anal. Calcd for C29H51O2NSi: C, 73.51; H, 10.85. Found: C,
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-23-n or -5r-ch ol-20-en -
15â-ol (31). To a solution of methyltriphenylphosphonium
bromide (1.53 g, 4.28 mmol) in THF (5 mL) cooled to 0 °C was
added a solution of BuLi in hexanes (2.7 mL, 4.28 mmol). The
mixture was stirred at 0 °C for 15 min, warmed to rt, and
stirred for an additional 20 min. A solution of 25 (875 mg, 1.95
mmol) in THF (5 mL) was added dropwise at rt, and the
resulting solution was then refluxed for 3 h. After being cooled
to rt, it was quenched with a saturated NH4Cl solution. The
aqueous layer was extracted with EtOAc, and the combined
organic layers were dried over MgSO4 and condensed under
vacuum. Purification of the residue by flash chromatography
on silica gel (4/1 hexane EtOAc) gave 31 as a white solid (630
1
mg, 73%). 500-MHz H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.70
(ddd, J ) 4.1, 10.6, 12.5, 1H, H-9R), 0.81 (s, 3H, H-18), 0.83
(s, 3H, H-19), 0.88 (s, 9H, (CH3)3CSiO), 0.94 (dd, J ) 5.7, 11.5,
1H, H-14R), 0.95 (m, 1H, H-1R), 1.02 (dddd, J ) 5.4, 12.7, 12.7,
12.7, 1H, H-7R), 1.10 (m, 1H, H-5R), 1.13 (ddd, J ) 4, 12.7,
12.7, 1H, H-12R), 1.24-1.38 (m, 1H, H-6R), 1.29 (m, 1H,
H-11â), 1.31 (m, 1H, H-6â), 1.34 (m, 1H, H-4â), 1.44 (m, 1H,
H-4R), 1.45 (m, 1H, H-2â), 1.54 (m, 1H, H-11R), 1.68 (m, 1H,
H-1â), 1.69 (m, 1H, H-2R), 1.71 (m, 1H, H-8â), 1.76 (s, 3H,
H-21), 1.81 (m, 1H, H-12â), 1.82 (m, 1H, H-16â), 1.92 (dddd, J
) 12.7, 3.5, 3.5, 3.5, 1H, H-7â), 1.94 (dd, J ) 7.3, 7.3, 1H,
H-17R), 2.25 (ddd, J ) 14.6, 7.9, 7.9, 1H, H-16R), 3.55 (dddd,
J ) 4.6, 4.6, 10.9, 10.9, 1H, H-3R), 4.28 (ddd, J ) 2.4, 5.7, 7.9,
1H, H-15R), 4.74 (s, 1H, H-22), 4.87 (s, 1H, H-22′). 75-MHz
13C NMR: δ -4.78 (2C), 12.18, 15.25, 18.09, 21.02, 24.36, 25.80
(3C), 28.48, 31.44, 31.62, 31.81, 35.60, 37.09, 38.47, 38.51,
40.22, 42.77, 45.11, 54.97, 57.26, 60.70, 70.71, 72.09, 111.23,
144.89. IR (cm-1): 2932, 2857, 1640. Mass spectrum m/e (PCI:
isobutane): 429 (M+ - 18), 297 (M+ - 150, 100). Anal. Calcd
for C28H50O2Si: C, 75.27; H, 11.28. Found: C, 75.15; H, 11.30.
73.52; H, 10.91. Mp (°C): 172-173. [R]25 -9 (c ) 1, CHCl3).
D
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-15â-h yd r oxy-5r-ch ol-
esta n -23-on e (35). To a solution of 34 (350 mg, 0.74 mmol)
in benzene (7 mL) was added at rt a 2 M solution of isobutyl-
magnesium bromide in ether (1.84 mL). The reaction mixture
was then brought to reflux and stirred for 4 h. After cooling
to rt, it was quenched with a saturated NH4Cl solution. The
aqueous layer was extracted with EtOAc, and the combined
organic layers were dried over MgSO4 and condensed under
vacuum. Purification of the residue by flash chromatography
on silica gel (6/1 hexane EtOAc) gave 35 as a white solid (321
Mp (°C): 139-140. [R]25 -16 (c ) 1, CHCl3).
D
3â-[(ter t-Bu t yld im et h ylsilyl)oxy]-23-n or -5r-ch ola n e-
15â,22-d iol (32). To a nitrogen-purged flask containing bo-
rane-methyl sulfide complex (0.38 mL, 4.07 mmol) cooled to
0 °C was added cyclohexene (0.82 mL, 8.14 mmol) dropwise.
The mixture was stirred at 0 °C for 30 min and then diluted
with THF (6 mL). A solution of 31 (605 mg, 1.35 mmol) in THF
(6 mL) was then added dropwise, and the reaction mixture
1
mg, 82%). 500-MHz H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.67

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)
J . Org. Chem., Vol. 64, No. 7, 1999 2483
1
(ddd, J ) 3.8, 10.6, 12.4, 1H, H-9R), 0.83 (s, 3H, H-19), 0.87
(m, 1H, H-14R), 0.88 (s, 9H, (CH3)3CSiO), 0.90 (d, J ) 6.5, 3H,
H-26), 0.91 (d, J ) 6.5, 3H, H-27), 0.92 (d, J ) 6, 3H, H-21),
0.95 (m, 1H, H-1R), 0.97 (s, 3H, H-18), 0.99 (m, 1H, H-7R),
1.09 (m, 2H, H-12R, H-17R), 1.10 (m, 1H, H-5R), 1.24-1.38
(m, 1H, H-6R), 1.31 (m, 2H, H-6â, H-11â), 1.33 (m, 1H, H-16â),
1.34 (m, 1H, H-4â), 1.44 (m, 1H, H-4R), 1.45 (m, 1H, H-2â),
1.50 (m, 1H, H-11R), 1.67 (m, 1H, H-1â), 1.69 (m, 1H, H-2R),
1.72 (dddd, J ) 3.6, 12.4, 12.4, 12.4, 1H, H-8â), 1.89 (dddd, J
) 12.4, 3.6, 3.6, 3.6, 1H, H-7â), 1.92 (ddd, J ) 12.4, 3.3, 3.3,
1H, H-12â), 2.11 (m, 1H, H-22), 2.12 (m, 1H, H-20), 2.13 (m,
1H, H-25), 2.24 (d, J ) 7, 2H, H-24), 2.33 (ddd, J ) 15, 7.9,
7.9, 1H, H-16R), 2.42 (d, J ) 12.4, 1H, H-22′), 3.55 (dddd, J )
4.9, 4.9, 10.8, 10.8, 1H, H-3R), 4.19 (dd, J ) 5.7, 5.7, 1H,
H-15R). 75-MHz 13C NMR: δ -4.78 (2C), 12.14, 14.60, 18.09,
19.62, 20.91, 22.40, 22.51, 24.36, 25.80 (3C), 28.46, 31.25,
31.40, 31.81, 32.05, 35.53, 37.05, 38.49, 40.89, 41.20, 42.28,
45.03, 50.26, 52.31, 54.75, 56.27, 61.01, 70.25, 72.10, 211.32.
IR (cm-1): 2933, 2857. Mass spectrum m/e (PCI:isobutane):
515 (M+ - 18, 100), 383 (M+ - 150). Anal. Calcd for C33H60O3-
Si: C, 74.37; H, 11.35. Found: C, 74.29; H, 11.43. Mp (°C):
7.0, CHCl3). Mp: 179-180 °C. 500 MHz H NMR δ 5.35 (ddd,
J ) 4.8, 2.6, 1.9, 1H, CdCHCH2), 3.89-3.99 (m, 4H, (CH2O)2C),
3.65 (ddd, J ) 8.6, 8.6, 6.0, 1H, CHOH), 2.57 (ABddd J AB
)
14.0, J ) 2.9, 2.9, 2.9, 1H, 4-CHH), 2.12 (ABd, J AB ) 14.0, 2.9,
1H, 4-CHH), 2.03-2.10 (m, 1H, 16-CHH), 1.98 (ABddd, J AB
)
17.5, J ) 5.4, 5.4, 2.9, 7-CHH), 1.74-1.85 (m, 3H), 1.40-1.70
(m, 7H), 1.03-1.13 (m, 2H), 1.04 (s, 3H, 19-CH3), 0.91-0.99
(m, 1H), 0.76 (s, 3H, 18-CH3). 75 MHz 13C NMR δ 140.4, 122.0,
109.5, 81.8, 64.4, 64.1, 51.2, 49.7, 42.6, 41.7, 36.6, 36.4, 36.2,
31.8, 31.2, 30.9, 30.3, 23.3, 20.4, 18.7, 10.8. IR (cm-1) 3474,
2950, 1460. Mass spectrum (CI) m/e 333 (M + 1), 315 (M -
OH). Anal. Calcd for C21H32O3‚0.3xH2O: C, 74.65; H, 9.72.
Found: C, 74.44; H, 9.64.
3,3-(Eth ylen edioxy)-17â-m eth oxy-5-an dr osten e (37). Us-
ing a procedure reported by Heathcock,40 a solution of 950 mg
(2.85 mmol) of 36 in 10 mL of dry THF was added dropwise to
a stirred suspension of 490 mg (4.30 mmol) of 35% KH
(rendered oil free) in 14 mL of THF. The mixture was stirred
for 30 min, and 610 mg (4.30 mmol) of CH3I was added
dropwise. After stirring overnight at rt, the reaction was
quenched with water, followed by removal of most of the
solvent in vacuo. The aqueous solution was extracted three
times with 20 mL portions of EtOAc. The combined extracts
were washed with brine and dried over anhydrous Na2SO4.
Evaporation of the solvent yielded a solid which was purified
by chromatography (30% EtOAc/hexane) to give 940 mg (95%)
182-183. [R]25 -15 (c ) 1, CHCl3).
D
(20R)-3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-5r-ch olesta n e-
15,23-d ion e (29a ). To a solution of 35 (140 mg, 0.26 mmol)
in CH2Cl2 (3 mL) containing some Celite was added PCC (135
mg, 0.6 mmol) in one portion. The reaction mixture was stirred
at rt for 1 h and then filtered through a pad of Celite. After
concentration in vacuo, the residue was subjected to column
chromatography (silica gel) using a 4/1 mixture of hexane/
EtOAc as the eluent to give pure 29a as a white solid (124
of ether 37. [R]589 ) -47.9 (c 7.0, CHCl3). Mp: 163-165 °C.
500 MHz H NMR δ 5.34 (ddd, J ) 4.5, 2.6, 1.9, 1H, CdCH),
Na
1
3.89-3.99 (m, 4H, (CH2O)2C), 3.35 (s, 3H, CHOCH3), 3.24 (dd,
J ) 8.6, 8.0, 1H, CHOCH3), 2.57 (ABddd J AB ) 14.3, J ) 2.9,
2.9, 2.9, 1H, 4-CHH), 2.12 (ABd, J AB ) 14.3, J ) 2.9, 1H,
4-CHH), 1.91-2.06 (m, 3H), 1.73-1.83 (m, 2H), 1.43-1.70 (m,
7H), 1.16-1.37 (m, 3H), 1.06 (ddd, J ) 12.1, 11.2, 5.1, 1H),
1.03 (s, 3H, 19-CH3), 0.97 (ddd, J ) 12.4, 10.8, 7.0, 1H), 0.77
(s, 3H, 18-CH3). 75 MHz 13C NMR δ 140.5, 122.0, 109.6, 90.8,
64.4, 64.1, 57.8, 51.5, 49.7, 42.6, 41.6, 37.8, 36.5, 36.2, 31.6,
31.2, 30.9, 27.5, 23.2, 20.5, 18.6, 11.2. IR (cm-1) 2939, 2874,
1670. Mass spectrum (CI) m/e 347 (M + 1), 315 (M - OCH3).
Anal. Calcd for C22H34O3: C, 76.26; H, 9.89. Found: C, 76.32;
H, 9.88.
1
mg, 90%). 500-MHz H NMR: δ 0.05 (s, 6H, (CH3)2SiO), 0.62
(ddd, J ) 3.6, 10.3, 12.2, 1H, H-9R), 0.77 (s, 3H, H-18), 0.80
(s, 3H, H-19), 0.83 (m, 1H, H-7R), 0.88 (s, 9H, (CH3)3CSiO),
0.90 (d, J ) 5, 3H, H-26), 0.92 (d, J ) 5, 3H, H-27), 0.93 (m,
1H, H-1R), 0.99 (d, J ) 6.5, 3H, H-21), 1.07 (m, 1H, H-5R),
1.22-1.40 (m, 2H, H-6R, H-12R), 1.27 (m, 1H, H-6â), 1.28 (m,
1Η, H-11â), 1.31 (m, 1H, H-4â), 1.43 (m, 1H, H-4R), 1.44 (m,
1H, H-2â), 1.55 (m, 1H, H-11R), 1.61 (m, 1H, H-17R), 1.62-
1.68 (m, 1H, H-12â), 1.65 (m, 1H, H-1â), 1.69 (m, 1H, H-2R),
1.71 (dddd, J ) 3.6, 12.4, 12.4, 12.4, 1H, H-8â), 1.75 (dd, J )
9.8, 18, 1H, H-16â), 2.06-2.10 (m, 1H, H-14R), 2.10 (m, 1H,
H-20), 2.13 (m, 1H, H-25), 2.19 (dd, J ) 9.6, 16.2, 1H, H-22),
2.24 (d, J ) 7, 2H, H-24), 2.33 (dd, J ) 3, 16.2, 1H, H-22′),
2.36 (dd, J ) 8.5, 18, 1H, H-16R), 2.64 (dddd, J ) 12.2, 3.6,
3.6, 3.6, 1H, H-7â), 3.55 (dddd, J ) 4.6, 4.6, 10.9, 10.9, 1H,
H-3R). 75-MHz 13C NMR: δ -4.78 (2C), 12.07, 12.85, 18.09,
20.01, 20.59, 22.36, 22.47, 24.40, 25.80 (3C), 28.14, 30.56,
31.60, 31.75, 31.79, 35.49, 37.05, 38.37, 39.69, 41.63, 42.34,
44.88, 49.78, 51.08, 52.53, 53.94, 65.94, 71.99, 210.47, 215.43.
IR (cm-1): 2933, 1735, 1707. Mass spectrum m/e (PCI:
isobutane): 531 (M+, 100), 513 (M+ - 18), 399 (M+ - 132).
Anal. Calcd for C33H58O3Si: C, 74.66; H, 11.01. Found: C,
3,3-(E t h ylen ed ioxy)-17â-m et h oxy-5-a n d r ost en -7-on e
(38). Using a procedure described by Kato,41 a mixture of 920
mg (2.65 mmol) of 37 and 10.4 g (40.0 mmol) of Collins reagent
in 30 mL of dry CH2Cl2 was stirred at rt for 12 h and then
poured into aqueous NaCl. The product was extracted with
CH2Cl2, and the extracts were washed with water, aqueous
copper sulfate, and brine and dried. After removal of the
solvent, the residue was purified on a silica gel column using
20% EtOAc/hexane as the eluent to give 766 mg (80%) of enone
38. [R]589 ) -73.4 (c 7.0, CHCl3). Mp: 203-204 °C. 500 MHz
Na
1H NMR δ 5.66 (d, J ) 1.9, 1H, CdCH), 3.90-4.00 (m, 4H,
(CH2O)2C), 3.34 (s, 3H, CHOCH3), 3.23 (dd, J ) 8.9, 7.3, 1H,
CHOCH3), 2.68 (ABd, J AB ) 14.7, J ) 2.2, 1H, 4-CHH), 2.37-
2.44 (m, 1H), 2.33 (ABd, J AB ) 14.7, 3.2, 1H, 4-CHH), 2.26
(dd, J ) 11.8, 11.2, 1H, 8-CH), 2.00-2.11 (m, 1H, 15-CHH),
1.83-1.95 (m, 3H), 1.71-1.77 (m, 1H), 1.43-1.67 (m, 6H), 1.33
(ddd, J ) 11.2, 11.2, 7.0, 1H), 1.21 (s, 3H, 19-CH3), 1.15 (ddd,
J ) 12.2, 12.2, 3.2, 1H), 0.77 (s, 3H, 18-CH3). 75 MHz 13C δ
201.9, 165.1, 126.7, 109.0, 89.9, 64.5, 64.4, 57.7, 49.7, 45.1, 45.0,
43.2, 41.6, 38.2, 36.6, 35.5, 30.9, 27.5, 25.55, 20.7, 16.7, 11.4.
IR (cm-1) 2942, 1664. Mass spectrum (CI) m/z 361 (M+1), 329
(M - OCH3). Anal. Calcd for C22H32O4: C, 73.30; H, 8.95.
Found: C, 73.23; H, 8.92.
74.53; H, 11.01. Mp (°C): 206-207. [R]25 +29 (c ) 1, CHCl3).
D
3â-[(ter t-Bu tyld im eth ylsilyl)oxy]-23â-h yd r oxy-16â,23-
cyclo-5r,14â-ch olesta n -15-on e (30). To a solution of 29a
(120 mg, 0.23 mmol) in ethanol (7 mL) and THF (2 mL) was
added an aqueous solution of NaOH (0.2 mL, 2 N). The
reaction mixture was stirred at rt for 17 h before being
neutralized by 10% HCl. It was then evaporated to dryness,
and the residue was dissolved in CHCl3 and dried. Purification
by flash chromatography (6/1 EtOAc/hexane) afforded the fully
functionalized C/D/E ring system of the pentacyclic steroid 30
(120 mg, 100%).
3,3-(Eth ylen ed ioxy)-5-a n d r osten -17â-ol (36).35 Using a
procedure described by Paquette,35 a mixture of 1.0 g (3.50
mmol) of testosterone, 4, 0.75 g (12.1 mmol) of ethylene glycol,
and 13 mg (0.070 mmol) of p-toluenesulfonic acid monohydrate
in 18 mL of benzene was refluxed for 24 h with continuous
azeotropic removal of water and excess ethylene glycol by
means of a Dean-Stark trap. The cooled mixture was diluted
with 20 mL of EtOAc and washed with saturated brine and
saturated aqueous NaHCO3, and dried over anhydrous Na2-
SO4. The solvent was removed in vacuo, and the residue was
purified by column chromatography on silica gel (2:1 hexanes-
3,3-(Eth ylen edioxy)-17â-m eth oxy-an dr ostan -7-on e (39).
Using a procedure described by Kato,41 small pieces of lithium
metal (190 mg, 27.0 mmol) were added to liquid ammonia (50
mL, freshly distilled from sodium metal) and the mixture was
stirred for a few minutes under nitrogen. A solution of 38 (490
mg, 1.36 mmol) in dry THF (7 mL) was added dropwise, and
stirring was continued at -60 °C for 30 min. An excess of
(40) Lodge, E. P.; Heathcock, C. H. J . Am. Chem. Soc. 1987, 109,
3353.
(41) Kato, M.; Kurihara, H.; Yoshikoshi, A. J . Chem. Soc., Perkin
Trans. 1 1979, 2740.
EtOAc) to give 0.98 g (85%) of ketal 36. [R]589 ) -45.2 (c
Na

2484 J . Org. Chem., Vol. 64, No. 7, 1999
Krafft et al.
NH4Cl (1.50 g, 35 mmol) was added cautiously, and the stirring
was continued while the ammonia was allowed to evaporate.
The residue was diluted with water and extracted with EtOAc.
The extract was then washed with brine and dried. Evapora-
tion left a white powdery solid which was passed through a
silica gel column using hexanes-EtOAc (4:1) to give 470 mg
in 1.2 mL of CH2Cl2 was cooled to 0 °C. To this cooled solution
was added 0.04 mL (0.36 mmol) of benzoyl chloride dropwise.
The resulting solution was then allowed to stir overnight. After
the reaction was complete, the reaction was diluted with 50
mL of CH2Cl2 and was successively washed with saturated
NaHCO3 and brine, dried over anhydrous Na2SO4, and con-
centrated. Chromatography of the resulting oil on a silica gel
column with 20% EtOAc/hexane (1:1) afforded 52 mg (93%) of
(95%) of ketone 39. [R]589 ) -48.1 (c 7.0, CHCl3). Mp: 152-
Na
154 °C. 500 MHz 1H NMR δ 3.88-3.95 (m, 4H, (CH2O)2C),
3.33 (s, 3H, CHOCH3), 3.24 (dd, J ) 8.3, 8.3, 1H, CHOCH3),
2.37 (dd, J ) 11.5, 11.2, 1H, 8-CH), 2.30 (ABd, J AB ) 13.7, J
) 13.1, 0.6, 1H, 6-CHH), 2.17-2.24 (m, 1H, 15-CHH), 2.02-
2.10 (m, 1H, 16-CHH), 2.01 (dd, J ) 12.4, 3.5, 1H, 6-CHH),
1.81-1.91 (m, 2H), 1.60-1.76 (m, 5H), 1.38-1.55 (m, 4H),
1.10-1.29 (m, 4H), 1.08 (s, 3H, 198-CH3), 0.74 (s, 3H, 18-CH3).
75 MHz13C NMR δ 211.8, 108.7, 89.8, 64.2, 64.1, 57.7, 54.9,
49.5, 45.6, 45.4, 44.0, 42.6, 37.6, 36.6, 35.8, 35.0, 30.9, 27.4,
24.2, 21.4, 11.5, 10.7. IR (cm-1) 3052, 2952, 1706. Mass
spectrum (CI) m/z 363(M + 1), 331(M - OCH3). Anal. Calcd
for C22H34O4: C, 72.89; H, 9.45. Found: C, 72.78; H, 9.42.
3,3-(Eth ylen ed ioxy)-7-(tr im eth ylsiloxy)-17â-m eth oxy-
6-a n d r osten e (40). Using a procedure described by Garst,42
benzoate 42 as a white solid. [R]589 ) +35.5 (c 7.0, CHCl3).
Na
Mp 82-83 °C. 500 MHz 1H NMR δ 8.06 (ddd, J ) 8.3, 2.0,
1.4, 2H, 2,6-PhH), 7.56 (dddd, J ) 7.3, 7.0, 1.3, 1.3, 1H, 4-PhH),
7.45 (dddd, J ) 8.0, 7.5, 1.6, 1.3, 2H, 3,5-PhH), 5.00 (dd, J )
11.6, 9.0, 1H, 6-CHOBz), 3.82-3.94 (m, 4H, (CH2O)2O), 3.44
(ddd, J ) 9.3, 9.3, 6.3, 1H, 7-CHOH), 3.34 (s, 3H, CHOCH3),
3.21 (dd, J ) 8.3, 8.3, 1H, 17-CHOCH3), 1.96-2.04 (m, 1H),
1.93 (ddd, J ) 12.6, 3.7, 3.3, 1H), 1.91 (d, J ) 5.6, 1H,
7-CHOH), 1.10-1.87 (m, 25H), 1.00 (s, 3H, 19-CH3), 0.93 (ddd,
J ) 11.3, 11.3, 4.0, 1H, 14-CH), 0.79 (s, 3H, 18-CH3). 75 MHz
13C NMR δ 167.4, 133.2, 130.2, 129.9, 128.5, 108.7, 90.2, 78.5,
77.9, 64.1, 64.0, 57.7, 51.7, 50.7, 45.3, 43.6, 41.7, 37.6, 36.0,
32.3, 30.5, 27.7, 25.9, 20.8, 12.5, 11.6. IR (cm-1) 3589, 2953,
1716, 1623. Mass spectrum (CI) m/z 485 (M + 1), 453, 363 (M
- PhCO2), 331. Anal. Calcd for C29H40O6‚2.0xH2O: C, 66.09;
H, 8.51. Found: C, 66.72; H, 7.60.
i
a solution of 0.29 mL (2.04 mmol) of Pr2NH in 3 mL of THF
was cooled to -78 °C, and 1.26 mL (2.02 mmol) of 1.6 M
n-butyllithium in THF was added dropwise. After the addition,
the resulting solution was allowed to stir for 30 min at -78
°C. A solution of 370 mg (1.02 mmol) of 39 in 5 mL of THF
was added dropwise over 5 min. The resulting solution was
stirred at -78 °C for 30 min followed by quenching with 0.26
mL (2.04 mmol) of TMSCl in 0.42 mL (3.06 mmol) of NEt3,
warmed to rt, and concentrated on a rotary evaporator. The
residue was diluted with water and extracted with EtOAc (30
mL, 3×). The combined extracts were washed with a saturated
bicarbonate solution and brine, dried over anhydrous Na2SO4,
and evaporated in vacuo. The residue was passed though a
pad of silica gel using 20% EtOAc/hexane, and the solvent was
evaporated to give 430 mg (97%) of enol ether 40. Mp: 196-
proton (δ)
NOE observations (%)
1
198 °C. 500 MHz H NMR δ 4.39 (dd, J ) 1.9, 1.8, 1H, CHd
18-CH3 (0.79)
9-H (0.93)
19-CH3 (1.00)
OCH3 (3.34)
17-H (3.21)
6-H (5.00)
OCH3 (0.5), 15-H (0.6), 8-H (0.4)
7-H (4.87), 5-H (9.67), and others
6-H (3.06), 8-H (4.7)
17-H (2.5)
OCH3 (6.2)
7-H (1.55), OH (4.94), 8-H (5.22), 19-H
5-H (7.39), OH (6.2), 6-H (1.52),
14-H (2.3), 9-H (4.1)
C(OTMS)), 3.89-3.97 (m, 4H, (CH2O)2C), 3.34 (s, 3H, CHOCH3),
3.20 (dd, J ) 8.3, 8.3, 1H, CHOCH3), 2.28 (dddd, J ) 13.7,
3.5, 3.5, 1.9, 1H), 1.73-2.03 (m, 5H), 1.51-1.68 (m, 3H), 1.36-
1.47 (m, 3H), 1.07-1.32 (m, 5H), 0.79 (s, 3H, 19-CH3), 0.73-
0.79 (m 1H), 0.77 (s, 3H, 18-CH3), 0.16 (s, 9H, (CH3)3Si).
3,3-(Eth ylen ed ioxy)-6r-h yd r oxy-7â-h yd r oxy-17â-m eth -
oxya n d r osta n e (41). Using a procedure described by Brown,43
to a stirred solution of 40 (420 mg, 0.97 mmol) in 8 mL of THF
was added 0.97 mL (0.97 mmol) of 1 M BH3‚THF in THF
dropwise at 0 °C. After stirring at rt for 2 h, the reaction was
quenched with ice chips followed by addition of 0.2 mL (3.33
mmol) of 30% aqueous H2O2 and 1.2 mL of 3 M aqueous KOH.
The resulting solution was stirred at rt for 3 h. After the
reaction was complete, the solution was diluted with 10 mL
of water and extracted with EtOAc (4 × 30 mL). The combined
extracts were washed successively with saturated NaHCO3
and brine and dried over anhydrous Na2SO4. After removing
the solvent, the crude product was purified by silica gel
chromatography with 50% EtOAc/hexane to give 247 mg (67%)
7-H (3.44)
6r-H yd r oxy-7â-h yd r oxy-17â-m e t h oxya n d r ost a n -3-
on e (43). A mixture of ketal 41 (150 mg, 0.39 mmol) and
p-TsOH (1.5 mg, 0.008 mmol) in 2 mL of acetone was stirred
at rt for 12 h. The solution was then diluted with 20 mL of
water and extracted with EtOAc (4 × 30 mL). The combined
organic layers were washed with saturated NaHCO3 and brine,
dried, and evaporated in vacuo. The crude product was purified
by chromatography with EtOAc/hexane (2/1) to yield 119 mg
(90%) of ketone 43. [R]589 ) +59.8 (c 7.0, CHCl3). Mp 171-
Na
1
173 °C. 500 MHz H NMR δ 3.34 (s, 3H, CHOCH3), 3.31 (ddd,
J ) 8.6, 8.6, 3.8, 1H, 6-CHOH), 3.22 (dd, J ) 8.6, 8.3, 1H, 17-
CHOCH3), 3.14 (ddd, J ) 8.6, 8.6, 3.8, 1H, 7-CHOH), 2.67
(ABdd, J AB ) 15.3, J ) 4.2, 2.2, 1H, 4-CHH), 2.29-2.43 (m,
4H), 2.22 (dd, J ) 14.2, 13.4, 1H, 4-CHH), 2.19 (d, J ) 4.1,
1H, 6-CHOH), 2.00-2.09 (m, 3H), 1.82-1.88 (m, 1H), 1.94
(ddd, J ) 12.4, 3.8, 2.9, 1H), 1.33-1,74 (m, 7H), 1.14-1.27
(m, 2H), 1.07 (s, 3H, 19-CH3), 0.88 (ddd, J ) 10.8, 10.8, 3.8,
1H, 14-CH), 0.80 (s, 3H, 18-CH3). 75 MHz 13C NMR δ 211.8,
90.0, 80.3, 74.8, 57.7, 51.3, 50.5, 49.0, 43.5, 40.5, 39.2, 38.2,
37.5, 35.8, 27.6, 26.0, 21.1, 12.7, 11.6. IR (cm-1) 3577, 2949,
1711. Mass spectrum (CI) m/z 337 (M + 1), 287. Anal. Calcd
for C20H32O4‚0.7xH2O: C, 68.82; H, 9.64. Found: C, 69.01; H,
9.35.
of diol 41. [R]589 ) +37.3 (c 7.0, CHCl3). Mp: 171-173 °C.
Na
500 MHz 1H NMR δ 3.88-3.97 (m, 4H, (CH2O)2O), 3.34 (s,
3H, CHOCH3), 3.23 (obscured ddd, J ) 8.6, 8.6, 4.1, 1H,
6-CHOH), 3.21 (dd, J ) 8.6, 8.6, 1H, 17-CHOCH3), 3.12 (ddd,
J ) 9.6, 9.6, 3.8, 1H, 7-CHOH), 1.99-2.07 (m, 3H), 1.96 (ddd,
J ) 12.4, 2.5, 2.5, 1H), 1.91 (ddd, J ) 12.4, 3.5, 3.2, 1H), 1.10-
1.71 (m, 13H), 0.87 (s, 3H, 18-CH3), 0.86 (ddd, J ) 11.4, 11.4,
4.3, 1H, 14-CH). 75 MHz 13C NMR δ 109.1, 90.3, 74.8, 64.2,
64.1, 57.7, 51.8, 50.7, 46.6, 43.6, 40.8, 37.7, 36.2, 35.6, 32.0,
30.8, 27.7, 26.0, 20.8, 12.6, 11.5. IR (cm-1) 3576, 2952. Mass
spectrum (CI) m/z 381 (M + 1), 363 (M - OH). Anal. Calcd for
C
22H36O5: C, 69.44; H, 9.54. Found: C, 69.20; H, 9.55.
3r-H yd r oxy-6r-h yd r oxy-7â-h yd r oxy-17â-m et h oxya n -
d r osta n e (44). To a solution of ketone 43 (47 mg, 0.14 mmol)
in THF at -78 °C was added dropwise 0.49 mL (0.49 mmol)
of 1 M L-Selectride as a THF solution. This solution was stirred
for 2 h at -78 °C and then allowed to warm to rt (1 h). The
reaction mixture was then hydrolyzed with 1 mL of water
followed by addition of 1 mL of 3 M KOH and 1 mL of 30%
3,3-(Eth ylen edioxy)-7â-h ydr oxy-17â-m eth oxyan dr ostan -
6r-yl Ben zoa te (42). A mixture of diol 41 (44 mg, 0.12 mmol),
NEt3 (0.086 mL, 0.60 mmol), and DMAP (1.0 mg, 0.008 mmol)
(42) Garst, M. E.; Bontiglio, J . N.; Grudoski, D. A.; Marks, J . J . Org.
Chem. 1980, 45, 2307.
(43) Brown, H. C.; Sharp, R. L. J . Am. Chem. Soc. 1966, 88, 5851.

Synthesis of the C/D/E and A/B Rings of Xestobergsterol-(A)
J . Org. Chem., Vol. 64, No. 7, 1999 2485
H2O2. After stirring for another 2 h, the aqueous phase was
saturated with NaCl, the organic phase was separated, and
the aqueous phase was extracted with three 30 mL portions
of EtOAc. The combined extracts were washed with brine (2
× 10 mL) and dried (NaSO4). After removing the solvent in
vacuo, the residue was purified by chromatography with
58.1, 53.8, 52.5, 44.8, 43.6, 42.1, 39.0, 37.1, 33.7, 31.1, 29.1,
28.7, 27.1, 21.6, 12.8, 12.1. IR (cm-1) 3688, 3602, 3054, 2939.
Mass spectrum (CI) m/z 321 (M - 17), 303, 271. Anal. Calcd
for C20H34O4‚0.4xH2O: C, 68.77; H, 10.16. Found: C, 68.53;
H, 9.94.
EtOAc to give 43 mg (91%) of triol 44. [R]589 ) +39.0 (c 7.0,
Na
proton (δ)
NOE observations (%)
CH3OH). Mp: 215-217 °C. 500 MHz 1H NMR (CD3OD) δ 3.99
(dddd, J ) 2.9, 2.9, 2.9, 2.9, 1H, 3-CHOH), 3.29 (s, 3H, 17-
CHOCH3), 3.21 (dd, J ) 8.6, 8.3, 1H, 17-CHOCH3), 3.04 (dd,
3-H (3.99)
17-H (3.29)
6-H (3.21)
7-H (2.97)
4-HR (1.56), 4-Hâ (2.70), 2-HR/Hâ (5.26)
16-H (4.93), 12-H/16-H (10.66)
8-H (5.45), 4-Hâ (2.19), 19 CH3 (5.27), 7-H
5-H (7.25), 14-H (4.52), 9-H (2.87), 6-H
J
) 11.2, 8.6, 1H, 6-CHOH), 2.97 (dd, J ) 9.9, 8.6, 1H,
7-CHOH), 1.93-2.01 (m, 2H), 1.83-1.91 (m, 2H), 1.63 (ob-
scured ABddd, J AB ) 11.8, J ) 11.8, 11.8, 6.1, 1H, 15-CHH),
1.55-1.64 (m, 3H), 1.50 (ddd, J ) 10.3, 10.3, 10.3, 1H, 8-CH),
1.48 (ddd, J ) 11.2, 11.2, 5.2, 1H, 5-CH), 1.39 (obscured ABdd,
J AB ) 12.8, J ) 12.8, 3.2, 1H, 16-CHH), 1.38 (obscured ABdd,
J AB ) 12.4, J ) 12.4, 4.1, 4-CHH), 1.10-1.36 (m, 5H), 0.83
(ddd, J ) 11.2, 11.2, 3.8, 1H, 14-CH), 0.81 (s, 3H, 19-CH3),
0.73 (s, 3H, 18-CH3). 75 MHz 13C NMR δ 92.0, 81.6, 76.2, 66.5,
Ack n ow led gm en t. This work has been supported
by the National Institutes of Health and the National
Science Foundation.
J O982319W