The convergent synthesis of novel cytotoxic certonardosterol D2 from diosgenin

Article abstract of DOI:10.1016/j.tet.2007.11.028

Certonardosterol D₂, a polyhydroxysterol isolated from starfish Certonardoa semiregularis with exceptionally potent antitumor activity, was stereoselectively synthesized from natural rich diosgenin via the protocol of Julia olefination and Evan

Full text of DOI:10.1016/j.tet.2007.11.028

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 469e476
www.elsevier.com/locate/tet
The convergent synthesis of novel cytotoxic certonardosterol
D2 from diosgenin
*
Biao Jiang , He-ping Shi, Wei-sheng Tian, Wei-shan Zhou
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fengling Road, Shanghai 200032, PR China
Received 15 August 2007; received in revised form 7 November 2007; accepted 9 November 2007
Available online 12 November 2007
Abstract
Certonardosterol D2, a polyhydroxysterol isolated from starfish Certonardoa semiregularis with exceptionally potent antitumor activity, was
stereoselectively synthesized from natural rich diosgenin via the protocol of Julia olefination and Evans aldol reaction.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Polyhydroxysterol; Certonardosterol; Julia olefination; Evans aldol reaction
1. Introduction
OH
Julia Olifination
15
Evans Aldol Reaction
Global research aimed at the discovery of novel and clini-
cally useful antitumor agents from marine organisms con-
tinues at a remarkably active pace. Search for the natural
products in marine life has led to the discovery of a number
of biologically active polyhydroxysterols. These compounds
have shown promise as leading agents for the development
of novel therapeutics.1 Starfish are known to be a rich source
of structurally unique and biologically active steroids, most of
which do not have any counterpart within the entire animal
kingdom.2 A family of novel polyhydroxysterols, certonardos-
terols, were isolated from the starfish Certonardoa semiregula-
ris in 2004. These steroids are always highly oxygenated and
often occur in very limited amounts. Among these compounds,
certonardosterol D2 (1) was found to be the most cytotoxic for
the target human cancer cells with ED50 of 0.01e0.15 mg/mL,
which was comparable to that of doxorubicin.3 Herein, we re-
port the first synthesis of this 3b,6a,15b-trihydroxy steroid.
Certonardosterol D2 (1) was established as (22E,24R)-24-
methyl-5a-cholest-22-ene-3b,6a,15b,241-tetrol (Fig. 1). During
the last century, the chemistry of spirostanes was intensively
studied.4 Natural rich plant sapogenins are relatively cheap
OH
Allylic Oxidation
Stereoselective Reduction
6
HO
OH
Hydroboration
Oxidation
Certonardosterol D2
1
Fig. 1. Synthesis of certonardosterol D2 from diosgenin.
raw materials for the synthesis of a number of medicinally
important steroids.5 One of the major challenges for steroid
chemists was to elaborate an efficient degradation route
from spirostanol to the C19, C21 and C22 steroids.6 Espe-
cially, C22 carbonyl steroids proved to be useful precursors
for the synthesis of continental and marine steroids, such as
brassinolide,6b squalamine,7 and other marine steroids. Little
progress was reported for the degradation of spirostanes to
C22 steroids, which were usually obtained as byproducts in
different reactions of sapogenins. Only recently, Iglesias-
Arteaga obtained the C22-steroid bisnorcholanic lactone by the
Beckmann rearrangement of 23-hydroxyimino-sapogenins
promoted by BF3$Et2O in acetic acid.8 In an intensive study,
it was found that direct cleavage of C22eC23 bond of sapoge-
nins was achieved by a simple reaction of sapogenins with
* Corresponding author. Tel.: þ86 21 54925201; fax: þ86 21 64166128.
E-mail address: jiangb@mail.sioc.ac.cn (B. Jiang).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.028

470
B. Jiang et al. / Tetrahedron 64 (2008) 469e476
peroxyacetic acid, in the presence of catalytic amount of
H2SO4 and iodine,9 which provided the skeleton of D2.
Despite the fact that the Claisen or IrelandeClaisen rearrange-
ment has been widely reported for synthesis of the (22E )-
steroids bearing an R or S alkyl constituent at C-24 based on
the stereochemical transformation of C-22 allylic hydroxyl
configuration of steroidal side chain, the stereoselectivity did
not offer satisfactory results.10 With the intent to search for
a universal methodology for the stereoselective synthesis of
side chains of the family of certonardosterols, we exploited
a convergent synthesis strategy via the Julia olefination11 of
steroidal aldehyde with a chiral alkyl sulfone. The 24R-hy-
droxyl methyl group was introduced stereoselectively by
Evans aldol reaction.12 It was observed that C-15b hydroxyl
could be transferred from C-16-oxo in sapogenins13 (Fig. 1).
Pd(OH)2/C and subsequent reduction by NaBH4 afforded the
C-15 alcohol 11 in 89% yield. The chemical shift for the D-
ring 15b-hydroxyl CeH in 11 gave a triplet (J¼6.0 Hz) at
4.20 ppm, which implies a 15b-hydroxy configuration13b in
both chemical shift and coupling constant. After masking C-
15b hydroxyl in 11 with methoxy methyl chloride and hydro-
lysis of C-22 acetyl in 12, DesseMartin oxidation of the free
alcohol afforded C-22 aldehyde 14 quantitatively (Scheme 2).
The construction of steroidal fragment was followed by fo-
cusing the attention on the synthesis of chiral C6 piece of ste-
roidal side chain. The (2S )-butyl sulfone 19 was obtained with
high enantiomeric purity in five steps as shown in Scheme 3.
After the generation of the titanium enolate from (R)-15 by
treatment with TiCl4 in the presence of Hunig’s base according
to the protocol of Evans,14 the subsequent reaction with s-tri-
oxane afforded the aldol adduct, which was transferred into
methoxy methyl ether directly. Purification by silica gel chro-
matography afforded the desired (2R0,2S )-16 in 81% yield
(two steps) with >99% de. Removal of the chiral auxiliary
with LiBH4 gave alcohol 17 in 78% yield. Alcohol 17 was
subjected to a Mitsunobu reaction with 2-mercaptobenzothi-
azole affording (2S )-butyl sulfide 18 quantitatively, which was
further oxidized into sulfone 19 by hydrogen peroxide and
ammonium molybdate tetrahydrate in 80% yield.
2. Results and discussion
By using the practical method,9 chlorogenin (3), which was
obtained from natural rich diosgenin (2) via hydroboration
(BH3/THF, 0 ꢀC) and oxidation with hydrogen peroxide, was
degraded to lactone 4 in 85% yield (Scheme 1).
Next, attention was directed toward the transposition of the
C-16-oxy in D-ring to the C-15b hydroxyl. Riccards found
that the stereochemical outcome of the C-15 carbonyl reduc-
tion was strongly dependent on the C-16 and C-17 hybridiza-
tion. C-15b hydroxyl could be established by the reduction of
the C-15 ketone stereoselectively.13b Thus, after switching the
hydroxyl groups of lactone 4 to methoxy methyl ethers, the
lactone 5 on being reduced with LiAlH4 gave the diol 6 in
99% yield. The C22-primary hydroxyl group in the side chain
was chemoselectively protected as its acetate (Ac2O/DMAP/
Et3N). Dehydration of the 16b-alcohol 7 with phosphorous
oxychloride in pyridine according to the report of Williams13a
afforded a mixture of 16-chloro steroid 8 and the desired olefin
9 (in the ratio of 2:1) in 89% yield. Compound 8 could be eas-
ily converted into olefin 9 by treatment with Li2CO3/LiCl in
DMF at 120 ꢀC. C-15 ketone in D-ring was generated by the
allylic oxidation using Na2Cr2O7$2H2O and N-hydroxy succi-
nimide in 76% yield. Hydrogenation of 10 over 20 wt %
With the C22 steroidal aldehyde 14 and (2S )-butyl sulfone
19 fragments in hand, their assembly was finally undertaken.
A Julia olefination between aldehyde 14 and butyl sulfone
19 was performed with the LiHMDS at ꢁ78 ꢀC, which pro-
vided E-olefin 20 exclusively in 57% yield. Global removal
of the four methoxy methyl ether protection groups in 20
gave certonardosterol D2 (1) in 98% yield. The spectral data
of synthetic certonardosterol D2 were consistent in all respects
with that reported for the natural product3 (Scheme 4).
3. Conclusions
We accomplished the first synthesis of certonardosterol D2
in 18 steps in an 18% overall yield from the commercially
available diosgenin. The strategy for obtaining the C-15b hy-
droxy steroid from a C-16b hydroxy steroid was shown to be
O
O
1. BH3/THF, 0 °C
2. 30%H2O2,
NaOH 0 °C to rt
O
O
91% (2 steps)
HO
HO
OH
3
Diosgenin 2
O
1. I2, H2SO4(con.),
CH3CO3H, HOAc, r.t
2. 5N NaOH, rt
O
85% (2 steps).
HO
OH
4
Scheme 1. Synthesis of bisnorcholanic lactone 4.

B. Jiang et al. / Tetrahedron 64 (2008) 469e476
471
O
OH
OH
O
MOMCl, i-Pr2NEt,
CH2Cl2, reflux
LiAlH4, THF, 0 °C
4
96%
99%
RO
RO
OR
OR
5
6
Ac2O, CH2Cl2,
DMAP, Et3N, 0°C
LiBr, Li2CO3,
DMF, 120 °C
91%
80%
POCl3,
pyridine
89%
OAc
OAc
OAc
OH
Cl
+
RO
RO
RO
OR
OR
OR
9
8:9 = 2:1
8
7
.
NOS, Na2Cr2O7 H2O
acetone, 50 °C
76%
OAc
OAc
1. H2, 20% Pd(OH)2/C
MeOH, rt
2. NaBH4, THF, H2O
MOMCl, i-Pr2NEt,
CH2Cl2, 30 °C
89% (two steps)
99%
O
OH
RO
RO
OR
OR
10
11
O
OAc
OH
10%KOH,
MeOH, rt
Dess-Martin
CH2Cl2, 0 °C
99%
99%
OR
OR
OR
RO
RO
RO
OR
13
OR
12
OR
14
R=MOM
Scheme 2. Synthesis of 15b,C-22 steroidal aldehyde 14.
1.TiCl4, i-Pr2NEt,
effective. Julia olefination was used to assemble the high steric
side chain for steroid stereoselectivity. This methodology pro-
vided a convenient strategy for diversity-originated synthesis
of steroids.
s-trioxane,CH2Cl2
0 °C
O
O
O
O
2. MOMCl, i-Pr2NEt
CH2Cl2, reflux
LiBH4, THF
0 °C- rt
O
N
O
N
81%(two steps)
78%
OMOM
Bn
15
Bn
16
4. Experimental section
S
2-mercaptobenzothiazole
HO
S
4.1. General remarks
DIAD, Ph3P, THF, 0 °C
99%
N
OMOM
17
OMOM
1H NMR and 13C NMR spectra were recorded at 300 and
500 MHz using a Varian EM-360A spectrometer with TMS
as the internal standard. Chemical shift (d) values were given
in parts per million. MS were recorded with HP-5989A spec-
trometer using the ESI method. The melting points were deter-
mined on an SGW X-4 melting point apparatus and were
uncorrected. Optical rotations were obtained with Perkine
Elmer Polarimeter 341 apparatus.
18
O
S
(NH4)6Mo7O24.4H2O
EtOH, 30%H2O2. rt
S
N
80%
O
OMOM
19
Scheme 3. Synthesis of (2S )-butyl sulfone 19.

472
B. Jiang et al. / Tetrahedron 64 (2008) 469e476
OMOM
OH
6M HCl
THF
LiHMDS,
THF, -78 °C
14
+
19
98%
57%
OMOM
OH
MOMO
HO
OH
1
OMOM
20
Scheme 4. Synthesis of certonardosterol D2.
4.1.1. Chlorogenin (3)15
extracted with CH2Cl2 (20 mLꢂ3). The combined organic ex-
tracts were washed with brine (30 mLꢂ2), dried over anhydrous
Na2SO4, filtered, and concentrated. Flash chromatography
(hexane/EtOAc¼3:1) provided 5 (7.2 g, 96%) as a white solid.
Mp 136e137 ꢀC. [a]D20 ꢁ16.1 (c 1.20, CHCl3). IR (KBr):
To a solution of diosgenin (2) (1.0 g, 2.4 mmol) in dry THF
(100 mL) under an argon atmosphere at 0 ꢀC, 1 M BH3 in THF
(7.2 mL, 7.2 mmol) was added slowly. The mixture was al-
lowed to stir overnight at room temperature. NaOH (10 N,
1.5 mL, 15 mmol) was added over 30 min at 0 ꢀC. Subse-
quently, 30% hydrogen peroxide (1.5 mL, 13 mmol) was
added and vigorous stirring was continued at room tempera-
ture for 2 h. Extraction with CH2Cl2 (20 mLꢂ3) and the com-
bined extracts were washed successively with 1 N HCl,
saturated NaHCO3, and brine, dried (anhydrous Na2SO4), fil-
tered, and concentrated in vacuo. Purification by column chro-
matography (Hexane/EtOAc¼1:3) gave 3 as a white solid
(950 mg, 91% yield). 1H NMR (300 MHz, pyridine-d5): d 4.54
(q, 1H, J¼7.5 Hz), 3.96e3.89 (m, 1H), 3.66 (dt, 1H, J¼10.8,
4.5 Hz), 3.59e3.55 (m, 1H), 3.51e3.44 (m, 1H), 3.01 (1H, br
d, J¼12.0 Hz), 2.24 (dt, 1H, J¼7.8, 3.9 Hz), 1.14 (d, 3H, J¼
6.6 Hz), 0.87 (s, 3H), 0.85 (s, 3H), 0.67 (d, 3H, J¼5.4 Hz).
2939, 1760, 1183, 1146, 1103, 1037, 912 cmꢁ1 1H NMR
.
(300 MHz, CDCl3): d 4.96e4.89 (m, 1H), 4.70, 4.53 (AB, 2H,
JAB¼6.9 Hz), 4.66 (s, 2H), 3.47e3.41 (m, 1H,), 3.34 (s, 3H),
3.33 (s, 3H), 3.30e3.28 (m, 1H), 2.55 (q, 1H, J¼7.5 Hz),
2.29e2.22 (m, 2H), 2.06 (dt, 1H, J¼12.0 Hz, 4.2 Hz), 1.28 (d,
3H, J¼4.5 Hz), 0.82 (s, 3H), 0.71 (s, 3H). 13C NMR (75 MHz,
CDCl3): d 181.2, 95.3, 94.4, 82.5, 75.9, 74.6, 58.9, 55.4, 55.1,
54.3, 53.6, 50.0, 41.7, 38.4, 38.1, 37.1, 36.5, 36.0, 33.5, 32.9,
29.4, 28.2, 20.4, 17.9, 13.7, 13.4. ESI-MS: 468.4 (MþNHþ4 ).
HRMS calcd for C26H42O6Naþ: 473.2862; found: 473.2874.
4.1.4. 3b,6a-Dimethoxymethyl-23,24-bisnor-5a-cholan-
16b,22-diol (6)
Compound 5 (1.0 g, 2.2 mmol) in dry THF (15 mL) was re-
duced with LiAlH4 (0.15 g, 3.9 mmol) at room temperature for
10 h. The reaction was quenched with wet Na2SO4 with cau-
tion. The gray precipitate was filtered and washed with THF
(10 mLꢂ3). The filtrate was partitioned between water and
THF. The aqueous layer was extracted with THF
(10 mLꢂ3). The combined organic extracts were washed
with brine (10 mLꢂ2), dried over anhydrous Na2SO4, filtered,
and concentrated to give pure compound 6 (1.0 g, 99%) as
a white solid. [a]2D0 ꢁ29.3 (c 1.30, CHCl3). IR (KBr): 2945,
4.1.2. 3b,6a,16b-Trihydroxy-23,24-dinor-5a-cholan-22-oic
acid-16-lactone (4)16
To a mixture of HOAc (60 mL) and H2SO4 (concd)
(0.9 mL), I2 (0.49 g, 1.9 mmol) was added and stirred for
30 min at room temperature. Then compound 3 (8.4 g,
19.4 mmol) was added and the mixture was further stirred
for 10 min. CH3CO3H (118.4 mL, 118 mmol, 1 M in HOAc)
was added dropwise. After 4 h, the reaction was saponified
with 5 N NaOH to pH¼13 at room temperature overnight.
The crude product was filtered and dried in vacuo. Flash chro-
matography (CH2Cl2/MeOH¼10:1) provided 4 (6.0 g, 85%)
1
2852, 1145, 1103, 1039 cmꢁ1. H NMR (300 MHz, CDCl3):
d 4.72, 4.54 (AB, 2H, JAB¼6.9 Hz), 4.67 (s, 2H), 4.38e4.36
(m, 1H), 3.56e3.54 (m, 1H), 3.48 (br, 3H), 3.35 (s, 6H),
2.24e2.17 (m, 3H), 0.94 (d, 3H, J¼6.9 Hz,), 0.87 (s, 3H),
0.82 (s, 3H). 13C NMR (75 MHz, CDCl3): d 95.2, 94.4,
76.1, 74.9, 72.4, 70.6, 62.2, 55.4, 55.1, 54.0, 53.6, 50.0, 42.9,
40.0, 38.2, 37.1, 36.5, 35.4, 33.7, 32.4, 29.4, 28.2, 20.8, 16.9,
13.4, 13.2. ESI-MS: 572.4 (MþNHþ4 ). HRMS calcd for
C26H46O6Naþ: 477.3185; found: 477.3187.
1
as a white solid. Mp 252e253 ꢀC. H NMR (300 MHz, pyri-
dine-d5): d 4.88 (br s, 1H), 3.89 (br s, 1H), 3.64 (br s, 1H),
2.97 (d, 1H, J¼11.4 Hz,), 2.65 (d, 1H, J¼4.5 Hz), 2.17e2.13
(m, 2H), 2.07e2.03 (m, 1H), 1.23 (d, 3H, J¼7.2 Hz), 0.82 (s,
3H), 0.71 (s, 3H). 13C NMR (75 MHz, pyridine-d5): d 181.0,
82.5, 70.7, 68.1, 58.8, 54.2, 54.0, 52.4, 42.4, 41.6, 38.0,
37.7, 36.5, 36.1, 33.8, 33.4, 33.1, 32.1, 20.6, 17.7, 13.6, 13.5.
4.1.3. 3b,6a-Dimethoxymethyl-16b-hydroxy-23,24-bisnor-
5a-cholan-22-oic acid-lactone (5)
4.1.5. 22-Acetoxy-3b,6a-dimethoxymethyl-23,24-bisnor-5a-
cholan-16b-ol (7)
Lactone 4 (6.0 g, 16.6 mmol) was dissolved in dry CH2Cl2
(80 mL), DIPEA (24 mL, 145 mmol) and MOMCl (6.9 mL,
90 mmol) were added slowly by syringe. The brown reaction
mixture was allowed to stir overnight under reflux. HCl (1 N)
was added to neutralize the excessive base. The mixture was
partitioned between water and CH2Cl2. The aqueous layer was
To a solution of compound 6 (0.8 g, 1.78 mmol), DMAP
(7 mg, 0.04 mmol) in CH2Cl2 (40 mL), triethylamine
(0.5 mL, 3.2 mmol) was added a solution of Ac2O (0.18 mL,
2.1 mmol) in CH2Cl2 (10 mL) at 0 ꢀC. After 3 h, the reaction
was quenched with saturated ammonium chloride (20 mL) and
the aqueous layer was extracted with CH2Cl2 (15 mLꢂ2). The

B. Jiang et al. / Tetrahedron 64 (2008) 469e476
473
combined organic extracts were washed with saturated
NaHCO3 (20 mLꢂ2), brine (20 mLꢂ2), dried over anhydrous
Na2SO4, filtered, and concentrated. Flash chromatography
(Hexane/EtOAc, 3:1 to 1:1) provided 7 (0.80 g, 91%) as
a white solid. Mp 89e90 ꢀC. [a]D20 ꢁ38.3 (c 0.40, CHCl3).
heated at 120 ꢀC and monitored by TLC. After reaction was
completed, water (2 mL) and 1 M HCl (4 mL) were added to
the mixture. The solution was extracted with CH2Cl2
(20 mLꢂ3). The combined organic extracts were washed with
brine (10 mLꢂ2), dried over anhydrous Na2SO4, filtered, and
concentrated. Flash chromatography (hexane/EtOAc¼7:1) pro-
vided 9 (305 mg, 80%) as a colorless oil.
IR (KBr): 3528, 2885, 1722, 1257, 1030, 908 cmꢁ1 1H
.
NMR (300 MHz, CDCl3): d 4.70, 4.53 (AB, 2H, JAB¼6.9 Hz),
4.67 (s, 2H), 4.32 (dd, 2H, J¼10.8, 3.3 Hz), 3.63 (dd, 1H, J¼
11.1, 7.8 Hz), 3.36e3.34 (m, 1H), 3.34 (s, 3H), 3.33 (s, 3H),
3.33e3.32 (m, 1H), 2.82 (d, 1H, J¼3.3 Hz), 2.06 (s, 3H),
1.05 (d, 3H, J¼6.9 Hz), 0.84 (s, 3H), 0.80 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 172.0, 95.2, 94.5, 76.0, 74.8, 71.8,
70.1, 58.1, 55.4, 55.1, 53.9, 53.6, 50.0, 42.5, 39.6, 38.2, 37.1,
36.5, 35.9, 33.7, 30.6, 29.5, 28.2, 21.0, 20.7, 16.9, 13.4, 13.1.
ESI-MS: 519.4 (MþNaþ). HRMS calcd for C28H48O7Naþ:
519.3319; found: 519.3292.
4.1.8. 22-Acetoxy-3b,6a-dimethoxymethyl-23,24-bisnor-5a-
chol-16-ene-15-one (10)
A solution of compound 9 (10 mg, 0.02 mmol), N-hydroxy
succinimide (5 mg, 0.04 mmol), and Na2Cr2O7$2H2O (10 mg,
0.03 mmol) in acetone (2 mL) was heated at 50 ꢀC. After 4 h,
additional N-hydroxy succinimide (5 mg, 0.04 mmol) was
added and the reaction was kept overnight. Saturated sodium
sulfite (10 mL) was added. The solution was extracted with
EtOAc (15 mLꢂ3). The combined organic extracts were
washed with brine (15 mLꢂ2), dried over anhydrous Na2SO4,
filtered, and concentrated. The crude product was purified by
flash chromatography (hexane/EtOAc¼3:1) to afford 10
(7 mg, 76%, 1 mg 9 was recovered) as a colorless oil. [a]D20
40.2 (c 2.00, CHCl3). IR (KBr): 2933, 2887, 1743, 1710,
4.1.6. 22-Acetoxy-16-chlor-3b,6a-dimethoxymethyl-23,24-
bisnor-5a-cholane (8) and 22-acetoxy-3b,6a-dimethoxy-
methyl-23,24-bisnor-5a-chol-16-ene (9)
POCl3 (0.19 mL, 2.0 mmol) was slowly added to a solution
of compound 7 (100 mg, 0.20 mmol) in dry pyridine (5 mL) at
0 ꢀC. The mixture was allowed to warm to room temperature
overnight. The reaction was then quenched with water
(10 mL) and diluted with EtOAc. The mixture was acidified to
pH 4 with 2 M HCl. The aqueous layer was extracted with
EtOAc (15 mLꢂ2). The combined organic extracts were
washed with brine (10 mLꢂ2), dried over anhydrous Na2SO4,
filtered, and concentrated. Flash chromatography (hexane/
EtOAc¼7:1) provided 8 (63 mg, 61%) and 9 (27 mg 28%) as
colorless oil. Compound 8: IR (KBr): 2936, 1738, 1238,
1
1230, 1041, 736 cmꢁ1. H NMR (300 MHz, CDCl3): d 5.68
(s, 1H,), 4.80, 4.54 (AB, 2H, JAB¼6.9 Hz), 4.67 (s, 2H), 4.13e
4.07 (m, 2H), 3.39e3.36 (m, 1H), 3.36 (s, 3H), 3.34 (s, 3H),
3.34e3.32 (m, 1H), 3.11 (dt, J¼12.6, 3.9 Hz), 2.80e2.74
(m, 1H), 2.01 (s, 3H), 1.14 (d, 3H, J¼7.2 Hz), 0.97 (s, 3H),
0.88 (s, 3H). 13C NMR (75 MHz, CDCl3): d 206.6, 183.5,
170.8, 125.5, 94.8, 94.4, 75.8, 73.7, 66.9, 63.2, 55.5, 55.1,
54.3, 50.1, 46.8, 37.0, 36.5, 32.3, 32.1, 30.9, 29.6, 29.4,
28.2, 23.3, 20.8, 20.3, 17.8, 13.4. ESI-MS: 510.3 (MþNHþ4 ).
HRMS calcd for C28H44O7Naþ: 515.3001; found: 515.2979.
1
1039 cmꢁ1. H NMR (300 MHz, CDCl3): d 4.62, 4.45 (AB,
2H, JAB¼6.9 Hz), 4.59 (s, 2H), 4.21 (dd, 1H, J¼11.8, 4.2 Hz),
4.02e3.97 (m, 1H), 3.85 (dd, 1H, J¼11.8, 7.2 Hz), 3.42e3.35
(m, 1H), 3.26 (s, 6H), 3.22e3.19 (m, 1H), 2.20e2.16 (m, 1H),
1.96 (s, 3H), 0.94 (d, 3H, J¼6.6 Hz), 0.73 (s, 3H), 0.60 (s,
3H). 13C NMR (75 MHz, CDCl3): d 171.0, 95.1, 94.4, 75.9,
74.6, 68.7, 64.7, 62.0, 55.4, 55.0, 53.1, 52.5, 49.9, 44.8, 39.3,
38.1, 38.0, 37.0, 36.3, 34.0, 33.0, 29.6, 29.3, 28.1, 20.9, 17.3,
13.2, 13.0. ESI-MS: 532.3 (MþNHþ4 ). HRMS calcd for
C28H46O6NaþꢁHCl: 501.3185; found: 501.3187. Compound
9: [a]2D0 ꢁ30.6 (c 1.1, CHCl3). IR (KBr): 2966, 2934, 1739,
4.1.9. 22-Acetoxy-3b,6a-dimethoxymethyl-23,24-bisnor-5a-
cholan-15b-ol (11)
Compound 10 (100 mg, 0.20 mmol) in MeOH (1 mL) was
subjected to hydrogenation over 20 wt % Pd (OH)2 on carbon
(30 mg) for 5 h. The catalyst was removed by filtration through
Celite. The filtrate was concentrated. The residue oil in MeOH
(2 mL) and THF (6 mL) was treated with NaBH4 (30 mg,
0.8 mmol) at 0 ꢀC for 2 h. HCl (1 M, 3 mL) was added. The
solution was extracted with THF (8 mLꢂ3). The combined
organic extracts were washed with saturated NaHCO3
(5 mLꢂ2), brine (15 mLꢂ2), dried over anhydrous Na2SO4, fil-
tered, and concentrated. Flash chromatography (hexane/EtOAc,
1:1) provided 11 (90 mg, 89%) as a colorless oil. [a]2D0 11.8 (c
1.15, CHCl3). IR (KBr): 3483, 2935, 1739, 1243, 1045,
1041, 1026 cmꢁ1 1H NMR (300 MHz, CDCl3): d 5.38 (s,
.
1H), 4.74, 4.55 (AB, 2H, JAB¼6.9 Hz), 4.68 (s, 2H), 4.13e
4.07 (m, 1H), 3.96e3.89 (m, 1H), 3.47e3.36 (m, 1H), 3.36 (s,
3H), 3.35 (s, 3H), 3.35e3.32 (m, 1H), 2.44e2.38 (m, 1H),
2.27e2.24 (m, 1H), 2.03 (s, 3H), 1.04 (d, 3H, J¼6.6 Hz), 0.86
(s, 3H), 0.75 (s, 3H). 13C NMR (75 MHz, CDCl3): d 171.1,
156.8, 122.5, 95.2, 96.5, 76.0, 74.8, 68.5, 56.6, 55.4, 55.1,
54.3, 50.3, 47.2, 38.1, 37.0, 36.7, 34.6, 32.7, 31.4, 31.1, 29.7,
28.3, 21.0, 20.9, 18.7, 16.1, 13.4. ESI-MS: 496.4 (MþNHþ4 ).
HRMS calcd for C28H46O6Naþ: 501.3188; found: 501.3187.
1
915 cmꢁ1. H NMR (300 MHz, CDCl3): d 4.73, 4.54 (AB,
2H, JAB¼6.9 Hz), 4.68 (s, 2H), 4.20 (t, 1H, J¼6.0 Hz), 4.04
(dd, 1H, J¼10.8, 3.3 Hz), 3.80 (dd, 1H, J¼10.5, 6.9 Hz),
3.47e3.45 (m, 1H), 3.41e3.37 (m, 1H), 3.35 (s, 6H), 2.34e
2.27 (m, 3H), 2.04 (s, 3H), 1.00 (d, 1H, J¼6.6 Hz), 0.94 (s,
3H), 0.85 (s, 3H). 13C NMR (75 MHz, CDCl3): d 171.4, 95.2,
94.4, 76.0, 74.9, 69.3, 60.3, 55.5, 55.1, 54.0, 52.9, 50.1, 42.4,
40.9, 40.6, 37.5, 37.3, 36.5, 35.4, 31.4, 30.1, 29.7, 29.5, 28.3,
21.0, 17.2, 14.6, 13.3. ESI-MS: 514.4 (MþNHþ4 ). HRMS calcd
for C28H48O7Naþ: 519.3311; found: 519.3292.
4.1.7. Conversion of compound 8 to 9
To a solution of compound 8 (412 mg, 0.80 mmol) in freshly
distilled DMF (4 mL), LiBr$H2O (210 mg, 2.0 mmol) and
Li2CO3 (205 mg, 2.8 mmol) were added. The mixture was

474
B. Jiang et al. / Tetrahedron 64 (2008) 469e476
4.1.10. 22-Acetoxy-3b,6a,15b-trimethoxymethyl-23,24-
bisnor-5a-cholane (12)
a colorless oil. [a]2D0 ꢁ13.6 (c 1.30, CHCl3). IR (KBr): 2933,
2852, 1725, 1449, 1148, 1041, 916 cmꢁ1. 1H NMR (300 MHz,
CDCl3): d 9.55 (d, 1H, J¼3.3 Hz) 4.70, 4.53 (AB, 2H,
JAB¼6.9 Hz), 4.68 (s, 2H), 4.61, 4.49 (AB, 2H, JAB¼6.9 Hz),
4.01 (t, 1H, J¼6.0 Hz), 3.51e3.42 (m, 1H), 3.37e3.36 (m,
1H), 3.36 (s, 3H), 3.35 (s, 3H), 3.33 (s, 3H), 2.49e2.40
(m, 1H), 2.31e2.24 (m, 3H), 1.12 (d, 1H, J¼6.9 Hz), 0.91 (s,
3H), 0.85 (s, 3H). 13C NMR (75 MHz, CDCl3): d 204.6, 96.1,
95.1, 94.4, 76.3, 76.0, 74.7, 59.5, 56.1, 55.4, 55.1, 54.0, 51.0,
50.2, 49.3, 43.0, 40.6, 37.4, 37.3, 37.1, 36.6, 30.2, 29.5, 28.3,
20.8, 14.6, 13.4, 13.3. ESI-MS: 514.4 (MþNHþ4 ). HRMS calcd
for C28H48O7Naþ: 519.3293; found: 519.3292.
To a solution of compound 11 (309 mg, 0.62 mmol) in
freshly distilled CH2Cl2 (20 mL), MOMCl (0.25 mL,
3.1 mmol) and DIPEA (0.80 mL, 4.3 mmol) were added sepa-
rately by syringe. The reaction was kept at 30 ꢀC overnight
and neutralized with 1 N HCl (5 mL). The mixture was parti-
tioned between water and CH2Cl2. The aqueous layer was ex-
tracted with CH2Cl2 (15 mLꢂ3). The combined organic
extracts were washed with brine (20 mLꢂ2), dried over anhy-
drous Na2SO4, filtered, and concentrated. Flash chromatogra-
phy (hexane/EtOAc, 1:1) provided 12 (335 mg, 99%) as a
colorless oil. [a]2D0 ꢁ4.7 (c 0.75, CHCl3). IR (KBr): 2936,
1
2853, 1740, 1239, 1046, 916, 757 cmꢁ1. H NMR (300 MHz,
4.1.13. (R)-4-Benzyl-3-((S )-2-((methoxymethoxy)methyl)-3-
methylbutanoyl)oxazolidin-2-one (16)
CDCl3): d 4.70, 4.50 (AB, 2H, JAB¼6.9 Hz), 4.68 (s, 2H),
4.63, 4.51 (AB, 2H, JAB¼6.9 Hz), 4.04 (d, 1H, J¼10.2 Hz),
3.98 (t, 1H, J¼5.7 Hz), 3.78 (dd, 1H, J¼10.5, 6.9 Hz),
3.47e3.44 (m, 1H), 3.37 (s, 3H), 3.37e3.35 (m, 1H), 3.35
(s, 3H), 3.34 (s, 3H), 2.31e2.24 (m, 3H), 2.04 (s, 3H), 1.01
(d, 1H, J¼6.6 Hz), 0.90 (s, 3H), 0.85 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 171.4, 96.2, 95.2, 94.5, 76.3, 76.1,
74.8, 69.3, 59.9, 56.1, 55.4, 55.1, 54.0, 52.9, 50.2, 42.6, 40.7,
38.0, 37.4, 37.2, 36.6, 35.5, 30.3, 29.5, 28.3, 21.0, 20.9, 17.2,
14.3, 13.4. ESI-MS: 558.3 (MþNHþ4 ). HRMS calcd for
C30H52O8Naþ: 563.3551; found: 563.3554.
To a solution of compound 15 (5.0 g, 19 mmol) in freshly
distilled CH2Cl2 (50 mL), TiCl4 (2.2 mL, 20 mmol) was added
dropwise at 0 ꢀC for 10 min under nitrogen. Then DIPEA
(3.7 mL, 21 mmol) was added for 1 h, following addition of
s-trioxane (2.0 g, 22 mmol) in 10 mL CH2Cl2. An additional
amount of TiCl4 (2.2 mL, 20 mmol) was added. The reaction
mixture was stirred for 4 h at 0 ꢀC and quenched by saturated
NH4Cl (50 mL). The organic layer was separated and the aque-
ous layer was extracted with CH2Cl2 (30 mLꢂ2). The com-
bined organic extracts were dried over Na2SO4, filtered, and
concentrated in vacuo. The yellow residue in freshly distilled
CH2Cl2 (60 mL) was treated with MOMCl (7.5 mL, 95 mmol)
and DIPEA (24 mL, 133 mmol) overnight under reflux. Water
(20 mL) was added to quench the reaction. The mixture was
neutralized with 1 N HCl and extracted with CH2Cl2
(20 mLꢂ3). The combined organic extracts were washed
successively by 1 N HCl (20 mLꢂ2), saturated NaHCO3
(25 mLꢂ3), brine (30 mLꢂ2), dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. Flash chromatography
(hexane/EtOAc, 7:1) provided compound 16 (5.16 g, 81%) as
a white solid. [a]2D0 ꢁ62.7 (c 1.00, CHCl3). IR (KBr): 1763,
4.1.11. 3b,6a,15b-Trimethoxymethyl-23,24-bisnor-5a-
cholan-22-ol (13)
Compound 12 (70 mg, 0.13 mmol) in MeOH (10 mL) was
treated with a solution of 10% KOH in MeOH (4 mL) at room
temperature for 6 h. The mixture was extracted with EtOAc
(20 mLꢂ3). The combined organic extracts were washed
with brine (20 mLꢂ2), dried over anhydrous Na2SO4, filtered,
and concentrated to give compound 13 (276 mg, 99%) as a col-
orless oil. [a]2D0 ꢁ11.1 (c 1.15, CHCl3). IR (KBr): 2964, 1261,
1
1095, 1027, 800 cmꢁ1. H NMR (300 MHz, CDCl3): d 4.71,
1
4.51 (AB, 2H, JAB¼6.9 Hz), 4.69 (s, 2H), 4.65, 4.53 (AB, 2H,
JAB¼6.9 Hz), 3.98 (t, 1H, J¼6.0 Hz), 3.61 (dd, 1H, J¼10.8,
3.0 Hz), 3.52e3.44 (m, 1H), 3.42e3.38 (m, 1H), 3.38 (s,
3H), 3.38e3.36 (m, 1H), 3.35 (s, 3H), 3.34 (s, 3H), 2.31e
2.24 (m, 3H), 1.04 (d, 1H, J¼6.6 Hz), 0.90 (s, 3H), 0.86 (s,
3H). 13C NMR (75 MHz, CDCl3): d 96.2, 95.1, 94.5, 76.4,
76.1, 74.8, 67.7, 60.0, 56.1, 55.4, 55.1, 54.0, 52.5, 50.2, 42.5,
40.7, 38.4, 38.0, 37.3, 37.2, 36.6, 30.2, 29.5, 28.3, 20.9, 16.8,
14.3, 13.4. ESI-MS: 516.4 (MþNHþ4 ). HRMS calcd for
C28H50O7Naþ: 521.3447; found: 521.3449.
1696, 1392, 1114, 1062 cmꢁ1. H NMR (300 MHz, CDCl3):
d 7.35e7.24 (m, 5H), 4.75e4.73 (m, 1H), 4.62 (s, 2H), 4.18e
4.09 (m, 3H), 3.93 (t, 1H, J¼9.3 Hz), 3.75 (dd, 1H, J¼9.3,
3.9 Hz), 3.35 (s, 3H), 3.25 (dd, 1H, J¼13.5, 3.0 Hz), 2.81
(dd, 1H, J¼13.5, 6.0 Hz), 2.06e2.00 (m, 1H), 0.99 (d, 3H, J¼
6.6 Hz), 0.97 (d, 3H, J¼6.6 Hz). 13C NMR (75 MHz, CDCl3):
d 174.9, 153.1, 135.2, 129.5, 128.8, 127.2, 96.3, 67.0, 65.5,
55.2, 48.8, 37.5, 28.5, 20.9, 19.4. ESI-MS: 353.2 (MþNaþ).
HRMS calcd for C18H25NO5Naþ: 358.1628; found: 358.1625.
4.1.14. (R)-2-((Methoxymethoxy)methyl)-3-methyl-
butan-1-ol (17)
4.1.12. 3b,6a,15b-Trimethoxymethyl-23,24-bisnor-5a-
cholan-22-al (14)
To a solution of compound 15 (4.86 g, 14.5 mmol) in Et2O
(30 mL) and THF (30 mL), a drop of water and LiBH4 (28 mL,
1 M in THF, 28 mmol) were added at 0 ꢀC. The reaction mix-
ture was allowed to stir overnight at room temperature. HCl
(1 N, 30 mL) was added with caution to quench the reaction.
The solution was extracted with EtOAc (30 mLꢂ2) and the
combined organic extracts were washed successively by satu-
rated NaHCO3 (20 mLꢂ3), brine (30 mLꢂ2), dried over anhy-
drous Na2SO4, filtered, and concentrated in vacuo. Flash
To a solution of alcohol 13 (322 mg, 0.65 mmol) in CH2Cl2
(10 mL), DesseMartin periodinane (1.05 g, 2.4 mmol) was
added at 0 ꢀC for 30 min. Saturated Na2S2O3 (3 mL) and satu-
rated NaHCO3 (9 mL) were added. The organic layer was sep-
arated and the aqueous layer was extracted with CH2Cl2
(10 mLꢂ2). The combined organic extracts were dried over
Na2SO4, filtered and concentrated in vacuo. Flash chromatogra-
phy (hexane/EtOAc, 1:1) gave aldehyde 14 (320 mg, 99%) as

B. Jiang et al. / Tetrahedron 64 (2008) 469e476
475
chromatography (hexane/EtOAc, 3:1) provided alcohol 17
(1.83 g, 78%) as a colorless oil. [a]2D0 7.6 (c 0.50, CHCl3). IR
LiHMDS (0.22 mL, 20% in THF, 0.22 mmol) was added
and the resultant mixture was stirred for 5 h at room tempera-
ture. The light yellow solution was quenched by saturated
NH4Cl (5 mL). The organic layer was separated and the aque-
ous layer was extracted with EtOAc (10 mLꢂ3). The com-
bined organic extracts were washed with brine (10 mLꢂ2),
dried over anhydrous Na2SO4, filtered, and concentrated in va-
cuo. Flash chromatography (hexane/EtOAc, 3:1) provided 20
(41 mg, 57%) as a colorless oil. [a]2D0 ꢁ17.9 (c 1.05, CHCl3).
IR (KBr): 2936, 2823, 1465, 1448, 1148, 1103, 1045,
1
(KBr): 3443, 2960, 2885, 1151, 1112, 1047, 920 cmꢁ1. H
NMR (300 MHz, CDCl3): d 4.59 (s, 2H), 3.71e3.58 (m, 4H),
3.34 (s, 3H), 2.62 (br s, 1H), 1.78e1.72 (m, 1H), 1.59e1.55
(m, 1H), 0.91 (d, 3H, J¼2.7 Hz), 0.89 (d, 3H, J¼2.4 Hz). 13C
NMR (75 MHz, CDCl3): d 96.6, 69.3, 64.0, 55.3, 46.4, 26.4,
20.2, 20.0. ESI-MS: 185.1 (MþNaþ). HRMS calcd for
C8H18O3Naþ: 185.1150; found: 185.1148.
4.1.15. (S )-2-(2-((Methoxymethoxy)methyl)-3-methyl-
917 cmꢁ1 1H NMR (300 MHz, CDCl3): d 5.30 (dd, 1H,
.
butylthio)benzo[d]thiazole (18)
J¼15.3, 7.8 Hz), 5.19 (dd, 1H, J¼15.5, 8.4 Hz), 4.71, 4.54
(AB, 2H, JAB¼6.9 Hz), 4.69 (s, 2H), 4.62, 4.49 (AB, 2H,
JAB¼6.9 Hz), 4.60 (s, 2H), 3.95 (t, 1H, J¼6.0 Hz), 3.52e3.43
(m, 3H), 3.39e3.37 (m, 1H), 3.37 (s, 3H), 3.36 (s, 3H), 3.35 (s,
3H), 3.34 (s, 3H), 2.33e2.25 (m, 2H), 1.03 (d, 3H, J¼6.6 Hz),
0.90 (s, 3H), 0.87 (d, 3H, J¼6.9 Hz), 0.86 (s, 3H), 0.82 (d, 3H,
J¼6.9 Hz). 13C NMR (75 MHz, CDCl3): d 138.7, 126.4, 96.5,
95.8, 95.1, 94.5, 76.1, 76.0, 74.9, 69.8, 60.2, 56.0, 55.4, 55.1,
54.1, 50.2, 48.7, 42.3, 40.8, 40.1, 38.8, 37.4, 37.2, 36.6, 30.2,
29.7, 29.5, 28.4, 28.3, 20.9, 20.7, 18.3, 14.4, 13.4. ESI-MS:
642.5 (MþNH4þ). HRMS calcd for C36H64O8Naþ: 647.4494;
found: 647.4493.
To a solution of alcohol 17 (441 mg, 2.7 mmol) in THF
(25 mL) under an argon atmosphere, Ph3P (1.07 g,
4.0 mmol), 2-mercaptobenzothiazole (683 mg, 4.0 mmol),
and DIAD (0.79 mL, 4.0 mmol) were added at 0 ꢀC. After
2 h, water (20 mL) was added. The organic layer was sepa-
rated and the aqueous layer was extracted with EtOAc
(20 mLꢂ2). The combined organic extracts were washed by
brine (15 mLꢂ2), dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. Flash chromatography (hexane/
EtOAc, 10:1) provided thioether 18 (845 mg, 99%) as a color-
less oil. [a]2D0 ꢁ45.1 (c 2.50, CHCl3). IR (KBr): 2916, 1459,
1429, 1041, 756 cmꢁ1. 1H NMR (300 MHz, CDCl3): d 7.85 (d,
1H, J¼8.1 Hz), 7.74 (d, 1H, J¼7.8 Hz), 7.40 (t, 1H, J¼
7.5 Hz), 7.27 (t, 1H, J¼7.5 Hz), 4.62 (s, 2H), 3.70 (dd, 1H,
J¼9.9, 4.8 Hz), 3.64e3.58 (m, 1H), 3.42e3.37 (m, 1H),
3.37 (s, 3H), 1.99e1.89 (m, 2H), 1.03 (d, 3H, J¼6.3 Hz),
1.01 (d, 3H, J¼6.9 Hz). 13C NMR (75 MHz, CDCl3): d 167.5,
153.2, 135.0, 125.9, 124.0, 121.3, 120.8, 96.6, 67.2, 55.3, 44.5,
33.4, 28.5, 20.0, 19.7. ESI-MS: 312.1 (MþHþ). HRMS calcd
for C15H22NO2Sþ2 : 312.1104; found: 312.1087.
4.1.18. (E )-(24R)-24-Methyl-5a-cholest-22-ene-3b,6a,
15b,241-tetrol (certonardosterol D2)
Compound 20 (20 mg, 0.032 mmol) in THF (4 mL) and
H2O (2 mL) was treated with 6 N HCl (2.5 mL) for 3 h at
room temperature. The mixture was extracted with EtOAc
(20 mLꢂ3). The combined organic extracts were washed suc-
cessively by saturated NaHCO3 (10 mLꢂ2), brine (10 mLꢂ3),
dried over anhydrous Na2SO4, filtered, and concentrated in va-
cuo. The crude product was purified by flash chromatography
(CH2Cl2/MeOH, 8:1) to afford certonardosterol D2 (14 mg,
4.1.16. (S )-2-(2-((Methoxymethoxy)methyl)-3-methyl-
butylsulfonyl)benzo[d]thiazole (19)
1
98%) as a white solid. [a]2D0 ꢁ3.9 (c 0.5, MeOH). H NMR
Compound 18 (424 mg, 1.36 mmol) in absolute EtOH
(15 mL) was oxidized with ammonium molybdate tetrahydrate
(3.36 g, 2.72 mmol) and H2O2 30% (4.6 mL, 40 mmol) at 0 ꢀC
for 2 h. The mixture was extracted with CH2Cl2 (20 mLꢂ3).
The combined organic extracts were washed with brine
(20 mLꢂ2), dried over anhydrous Na2SO4, filtered, and concen-
trated invacuo. Flash chromatography (hexane/EtOAc, 10:1 and
5:1) afforded sulfone 19 (375 mg, 80%) as a colorless oil. [a]D20
ꢁ6.3 (c 3.90, CHCl3). IR (KBr): 2961, 2887, 1473, 1328, 1147,
(500 MHz, CD3OD): d 5.30 (dd, 1H, J¼15.3, 8.5 Hz), 5.19
(dd, 1H, J¼15.3, 8.9 Hz), 4.12 (t, 1H, J¼5.7 Hz), 3.56e3.46
(m, 3H), 3.38 (td, 1H, J¼10.8, 4.5 Hz), 2.28e2.17 (m, 4H),
1.04 (d, 3H, J¼6.6 Hz), 0.95 (s, 3H), 0.90 (d, 3H, J¼
6.8 Hz), 0.86 (s, 3H), 0.83 (d, 3H, J¼6.8 Hz). 13C NMR
(100 MHz, CD3OD): d 140.6, 127.7, 72.0, 70.6, 70.0, 65.0,
62.2, 57.5, 55.7, 53.1, 52.8, 43.3, 42.8, 42.5, 41.8, 41.5, 38.6,
37.5, 33.0, 32.0, 31.6, 29.1, 22.2, 21.5, 21.4, 18.7, 15.3, 13.8.
ESI-MS: 471.4 (MþNaþ). HRMS calcd for C28H48O4Naþ:
471.3458; found: 471.3445.
1
1041, 763 cmꢁ1. H NMR (300 MHz, CDCl3): d 8.20 (d, 1H,
J¼7.8 Hz), 8.01 (d, 1H, J¼7.8 Hz), 7.66e7.58 (m, 2H), 4.49
(s, 2H), 3.68e3.60 (m, 3H), 3.53 (dd, 1H, J¼14.7, 3.9 Hz),
3.28 (s, 3H), 2.29e2.23 (m, 1H), 2.03e1.96 (m, 1H), 0.91 (d,
6H, J¼6.9 Hz). 13C NMR (75 MHz, CDCl3): d 166.2, 152.6,
136.7, 128.0, 127.6, 125.4, 122.3, 96.6, 66.7, 55.3, 53.7, 39.5,
28.7, 19.3, 19.2. ESI-MS: 366.1 (MþNaþ). HRMS calcd for
C15H21NO4S2Naþ: 366.0820; found: 366.0804.
Acknowledgements
We gratefully acknowledge Science and Technology Com-
mission of Shanghai Municipality for financial support
(064319016).
References and notes
4.1.17. (E )-(24R)-24-Methyl-3b,6a,15b,240-tetramethoxy-
methyl-5a-cholest-22-ene (20)
To a solution of aldehyde 14 (57 mg, 0.11 mmol) and sul-
fone 19 (47 mg, 0.14 mmol) in THF (1.5 mL) at ꢁ78 ꢀC,
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