Synthesis of Dihydrodiosgenin Glycosides as Mimetics of Bidesmosidic Steroidal Saponins

Article abstract of DOI:10.1002/ejoc.200300290

The focus of this work is the synthesis of bidesmosidic saponin mimetics. Therefore, dihydrodiosgenin derivatives, which differ from the natural compounds by reduction of the 22-(hemi) acetal were used as glycosyl acceptors. In preliminary studies, the dihydrodiosgenin glycosides 16, 17 and 19, as well as trisaccharide 22, were synthesized. The acceptors 10 and 14 were subjected to DMTST-mediated glucosylation for the synthesis of the chacotriose-substituted compound 3. For a selective 2,4-di-rhamnosylation of the dihydrodiosgenin glucopyranoside, differentiation of the glucose OH groups was achieved by selective benzoylation with 1-(benzoyloxy)benzotriazole. Reaction of the 3,6-di-O-benzoate 32 with the perbenzoylated ethyl thiorhamnopyranoside donor 15 gave the 2,4-di-rhamnosylated compound 33, together with the mono-rhamnosylated derivative. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300290

FULL PAPER
Synthesis of Dihydrodiosgenin Glycosides as Mimetics of Bidesmosidic
Steroidal Saponins
[a]
[b]
[b]
[a]
´
Rene Suhr, Martina Lahmann, Stefan Oscarson, and Joachim Thiem*
Keywords: Saponins / Carbohydrates / Steroids / Glycosylation / Mimetics
The focus of this work is the synthesis of bidesmosidic sap-
onin mimetics. Therefore, dihydrodiosgenin derivatives,
which differ from the natural compounds by reduction of the
22-(hemi) acetal were used as glycosyl acceptors. In prelim-
inary studies, the dihydrodiosgenin glycosides 16, 17 and 19,
as well as trisaccharide 22, were synthesized. The acceptors
10 and 14 were subjected to DMTST-mediated glucosylation
genin glucopyranoside, differentiation of the glucose OH
groups was achieved by selective benzoylation with 1-
(benzoyloxy)benzotriazole. Reaction of the 3,6-di-O-benzo-
ate 32 with the perbenzoylated ethyl thiorhamnopyranoside
donor 15 gave the 2,4-di-rhamnosylated compound 33, to-
gether with the mono-rhamnosylated derivative.
for the synthesis of the chacotriose-substituted compound 3. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
For a selective 2,4-di-rhamnosylation of the dihydrodios-
Germany, 2003)
Introduction
in this field,[4,5] and an effective synthesis of 3 have been
reported previously.[6] The aim of this work was to apply
an alternative, more general, synthetic pathway to target
structure 3 and its derivatives, as well as other dihydrodios-
genin glycosides, in particular, by altering the glycosylation
sequence, and through the use of benzoyl protecting groups.
In contrast, the pathway to 22-methyl acetal furostan sapo-
genins[7] and saponins is very complex, and requires many
more steps, as recently shown in the synthesis of a 3,26-
diglucopyranosyl derivative[8] and in the total synthesis of
2.[9]
The structurally diverse family of saponins, which are
found in plants, is of increasing interest, due to their mani-
fold biological activities. Many formulations of traditional
medicine appear to contain such compounds as active com-
ponents, and systematic screening of saponin-rich plant ma-
terial offers access to saponin libraries. However, it is often
the case that only small amounts of compound are available
by isolation from natural sources. Thus, their synthesis from
commercially or easily available starting materials is an
interesting alternative.
The naturally occurring bidesmosidic saponins 1 (GI50 ϭ
1.53Ϫ1.86 µg/mL, IC50 ϭ 2.7 µM, K562 cell line)[1,2] and 2
(IC50 ϭ 29 µM, HL-60 cell line)[3] were recently demon-
strated to show promising cytostatic activity. These mol-
ecules have enhanced lability, due to their hemiacetal or
acetal functionalities, respectively. In connection with vari-
ous more general approaches to such complex glycoconjug-
ate structures, we were interested in the synthesis of more
stable cyclic ether mimetics, such as 3, containing the easily-
available dihydrodiosgenin moiety. In this compound, the
furostenol aglycon is substituted at position 3β by 2,4-di-O-
Results and Discussion
(α--rhamnopyranosyl)-β--glucopyranose
(chacotriose)
and at position 26 by β--glucopyranose. Preliminary work
The present approach towards the formation of 3 and
other dihydrodiosgenin glycosides utilises thioglycosides as
donors. These compounds allow a flexible synthesis and are
stable to many protecting group manipulations.[10] Silyl and
p-methoxybenzyl ethers were selected as orthogonal pro-
tecting groups, allowing selective cleavage in the presence of
acyl protecting groups on the sugar and the double bond
of the steroid moiety. Commercially available diosgenin 4
[a]
Institut für Organische Chemie, Universität Hamburg,
Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Fax: (internat.) ϩ 49-40/428384325
E-mail: thiem@chemie.uni-hamburg.de
[b]
Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University,
10691 Stockholm, Sweden
Fax: (internat.) ϩ 46-8/154908
E-mail: s.oscarson@organ.su.se
Eur. J. Org. Chem. 2003, 4003Ϫ4011
DOI: 10.1002/ejoc.200300290
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4003

R. Suhr, M. Lahmann, S. Oscarson, J. Thiem
FULL PAPER
was used as the starting material for the steroid-acceptor ylation of 12. Diethyl ether was selected as more appropri-
synthesis. This compound leads to differentially protected ate solvent, and rhamnosylation of 5 and 12 was achieved,
dihydrodiosgenin derivatives via reductive spiroketal-open- giving 16 and 17 in 66 and 36% yields, respectively. It may
ing. Crucial to the synthesis was the final introduction of be possible to optimize this latter yield.
the 26-O-β--glucopyranose, and therefore a 26-O-pro-
tected 3β-hydroxy steroid acceptor was necessary. This ster-
oid acceptor in turn was glycosylated at the 3-position en
route to the construction of the chacotriose moiety.
Synthesis of Steroid Acceptors
The ring-opening reaction of the protected and unprotec-
ted spiroketals 4, 7 and 11 (Scheme 1) led to a 3β,26-di-
hydroxy furosten (dihydrodiosgenin, 5)[11,12] and its 3β-pro-
tected derivatives. In order to differentiate between the two
hydroxy groups in 5, the 3β position of the diosgenin 4 was
protected first, so that only the 26-OH group was free after
the ring-opening reaction. Two different ring-opening reac-
˚
tions were applied to diosgenin 4, and its derivatives 7[13]
Scheme 2. a: DMTST, 4-A mol. sieves, Et2O argon, 6 h, room
˚
temp.; b: DMTST, 4-A mol. sieves,CH2Cl2, argon, 4.5 h, room
and 11. Whereas 4 and 7 were opened by the classic Li-
temp.
AlH4/AlCl3 procedure to give 5[11,12] or 8, respectively, opti-
mal ring-opening of 11 to give 12 was achieved using so-
dium cyanoborohydride in acetic acid.[14]
Regioselective 2,3-Dirhamnosylation of 1,6-Protected
Glucopyranose
Attempts to achieve the 2,4-diglycosylation pattern by a
regioselective rhamnosylation using the 6-protected model
acceptor 21[18] led to the 2,3-dirhamnosylated compound 22
in good yield. Apparently, the 4-OH position of the glucose
acceptor showed considerably lower reactivity (Scheme 3).
Scheme 3. a: 1) NaOMe, MeOH, 2) TPBPSCl, pyridine, DMAP,
˚
47%; b: 1) DMTST, Et2O, 4-A mol. sieves, 2) Ac2O, pyridine, 60%
Scheme 1. a: LiAlH4/AlCl3/Et2O; b: Ac2O, pyridine; c: TBDPSCl,
imidazole, DMF; d: pMBnCl, NaH, DMF; e: TBAF, THF; f:
AcOH, NaBH3CN; g: TBDMSCl, pyridine; h: NaOMe, MeOH
Synthesis of Chacotriosyl Dihydrodiosgenin Derivatives
Two approaches to the synthesis of a chacotriose di-
hydrodiosgenin derivative, using different protecting groups
and regioselectivity strategies, were followed (Scheme 4). As
mentioned earlier, the main difficulty lies in the differen-
tiation of the equatorial 2-, 3- and 4-positions of the glu-
cose moiety.
One of the pathways investigated employed a predomi-
nantly 3,6-selective silylation[19] of β--thioglucopyranoside
23, followed by separation of the regioisomers and 2,4-ben-
zoylation to give 25. This donor reacted with the p-meth-
The 3β-hydroxy-26-protected compounds 10 and 14 were
obtained via a protection/deprotection sequence from 8 and
12 respectively. The 3β-O-TBDPS derivative 8 was con-
verted to the 26-O-p-methoxybenzyl derivative 10, whereas
12 was converted into the tert-butyldimethylsilyl- (TBDMS)
protected 14. In summary, the best sequence resulted in an
overall yield of 69% of 14 from diosgenin 4.
Mono- and Diglycosylation of Steroid Acceptors
In preliminary studies, the acceptors 5,[11,12] 12 and 14 oxybenzyl-protected steroid acceptor 10 under DMTST-
were glycosylated (Scheme 2). Employing the benzoylated mediated activation to give the steroid glucopyranoside 26
thiorhamnopyranoside 15[15] and thioglucopyranoside in high yield. Due to steric hindrance of the bulky TBDMS
18[16,17] as donors, the mono- or diglycosylated steroid de- groups, the subsequent debenzoylation under Zemplen con-
´
rivatives 16, 17 and 19 were obtained. Apparently, due to ditions was rather difficult. Even more difficult was the 2,4-
the solubility of the promoter dimethyl(methylthio)sulfoni- di-rhamnosylation using the thioglycoside donor 15[15] with
umtriflate (DMTST) in dichloromethane, the reaction con- DMTST-mediated activation in diethyl ether under anhy-
ditions were too vigorous, giving a poor yield in the glucos- drous conditions. An inseparable mixture of the chacotriose
4004
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4003Ϫ4011

Synthesis of Dihydrodiosgenin Glycosides
FULL PAPER
Scheme 4. a: NaOMe/MeOH; b: TBDMSCl, NEt3, DMAP, DMF, 48 h, room temp.; c: benzoyl chloride, pyridine, DMAP, 0 °C Ǟ room
˚
temp., 5 d; d: DMTST, Et2O, 4-A mol. sieves, argon or N2; e: 1-BBTZ, NEt3, CH2Cl2
substituted steroid 28a and the 2-rhamnopyranosylated glycosylation of thioglycoside donors then gave the target
steroid glucopyranoside 28b was obtained.
structures.
In view of these difficulties, an alternative, improved
pathway was followed. This time, the differentiation of the
glucose positions was achieved at the level of the steroid
glucopyranoside. Thus, the silylated steroid acceptor 14 was
glucosylated employing the benzoylated thioglucopyrano-
side 29[16,17] under DMTST-mediated conditions. The glu-
costeroid 30 thus obtained was debenzoylated under
Experimental Section
General Remarks: Thin-layer chromatography was carried out on
pre-coated plates of silica gel 60 (F254, Merck) with detection by
UV absorption or spraying with 20% ethanolic sulfuric acid and
subsequent heating. Column chromatography was performed by
the flash technique on silica gel 60 (230Ϫ400 mesh, 40Ϫ63 µm) by
Merck, Machery-Nagel or ICN using the given solvents as eluents
(PE ϭ petroleum ether, EA ϭ ethyl acetat). NMR spectra were
´
Zemplen conditions.
Pelyvas et al.[20] reported the 3,6-selective benzoylation of
´
β--glucopyranosides by in situ generated 1-benzoyloxy-
benzotriazole (1-BBTZ).[21Ϫ23] In our system, it appeared to
be better to prepare the pure 1-BBTZ first, and then apply
it to the selective benzoylation of 31. By this method, the
formation of aromatic by-products was avoided, and better
reaction control was obtained. By this procedure, com-
pound 32 was obtained in 33% yield, along with small
amounts of easily separable mono- and tri-benzoylated by-
products.
1
recorded with the Bruker spectrometers AMX-400 (400 MHz H,
100.67 MHz 13C) and DRX-500 (500 MHz H, 125.77 MHz 13C).
1
As internal standard, tetramethylsilane (δ ϭ 0.00 ppm) was added,
or, especially for silylated compounds, the solvent residual peak
was used.[24] Mass spectra were recorded with a Bruker BiflexTM III
MALDI-TOF-Mass spectrometer (positive reflector mode, Matrix:
DHB ϭ dihydroxybenzoic acid).[25] Melting points were deter-
mined on a Olympus BH polarising microscope with a Mettler
FP82 heating desk, or an Apotec melting point apparatus and are
Following rhamnosylation with 15[15] under DMTST-me-
diated conditions, the chacotriosyl steroid 33 was obtained,
again together with the 2-monorhamnoside 34. This com-
pound 33 represents a precursor en route to the 26-O-gluco-
sylated target structure 3. Further studies to complement
this synthetic part will be reported in due course.
not corrected. Optical rotations were determined with
a
PerkinϪElmer 241 PE polarimeter (NaD ϭ 589 nm). Elemental
analysis were performed in the microanalytical laboratory of the
Institute of Organic Chemistry of the University of Hamburg. Sol-
vents for reactions were distilled or dried before use. Dichlorometh-
ane (CaH2) and diethyl ether (sodium wire/benzophenone) for gly-
cosylation reactions were dried freshly under argon before use or
˚
stored over 4-A mol. sieves. Methanol was dried by refluxing over
˚
magnesium and subsequent distillation and stored over 3-A mol.
Conclusion
sieves. Commercially available anhydrous acetonitrile, anhydrous
pyridine and anhydrous DMF (Fluka) were used. Reagents were
used with the available purity offered by the producer. DMTST
was synthesized by a modified method according to the litera-
ture[26] and stored under argon with strict exclusion of moisture at
The syntheses of oligosaccharide mimetics of promising
cytostatic bidesmosidic saponins was achieved. Selectively
protected steroid derivatives were prepared for use as ac-
ceptors in the glycosylation reactions. DMTST-activated ca. Ϫ15 °C. It was warmed to room temperature before use. Reac-
Eur. J. Org. Chem. 2003, 4003Ϫ4011
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R. Suhr, M. Lahmann, S. Oscarson, J. Thiem
FULL PAPER
tions in inert gas atmosphere were performed under slight over
pressure of argon or nitrogen by the Schlenk or balloon technique
in glassware which was heated under vacuum before use.[27] Molec-
ular sieves were activated under high vacuum at ca. 130Ϫ250 °C
for several hours (usually overnight), cooled under slight over
pressure of argon or nitrogen and used freshly activated.
-23, -24) 65.06, 56.98, 50.01, 35.71, 31.54 (CH-8, -9, -14, -17,
-25) ppm.
(22R,25R)-3β-O-tert-Butyldiphenylsilyloxy-26-p-methoxybenzyloxy-
5-furosten (9): Compound 8 (630 mg, 0.96 mmol) was dissolved un-
der argon in anhydrous DMF (5 mL) in a 100-mL round-bottomed
flask with condenser. The mixture was cooled in an ice-bath and
sodium hydride (46 mg, 1.92 mmol) was added cautiously in small
General Procedure (GP). 1,2-trans-Selective Glycosylation with 2-O-
Acylated Thioglycosides by DMTST Activation: A donor/acceptor portions. The slightly yellow, foamy solution was stirred for 2.5 h.
ratio was chosen according to how valuable the compounds are
deemed to be. Generally, an excess of donor (1.2Ϫ1.5 equiv.) is
preferable. About 0.05 to 5 mmol donor and acceptor were placed
The mixture was again cooled in an ice-bath and p-methoxybenzyl
chloride (0.16 mL, 181 mg, 1.15 mmol) was added. After stirring
for 21 h under which time the temperature rose from 0 °C to room
in a 25 to 100 mL round-bottomed flask, and, especially for syrupy temperature, the reaction was quenched by the addition of meth-
compounds, were co-distilled three times with dry toluene. The
round-bottomed flask was flushed with argon and filled to about
3/4 with fresh anhydrous diethyl ether or diethyl ether/dichloro-
methane, 10:1. About 500 mg freshly activated molecular sieves per
0.1 mmol donor/acceptor were added, and the flask was closed
with a rubber septum or a nitrogen tap and equipped with an ar-
gon-filled balloon. The mixture was stirred for 1 h at room tem-
perature. Then 3 equiv. DMTST per 1 equiv. donor were added.
The reaction was stirred for about 1 to 4 h at room temperature
and monitored by TLC. For work-up, about 3 equiv. triethylamine
per 1 equiv. DMTST were added, and the mixture was stirred for
10 min. Large-scale reaction mixtures were filtered through Celite,
evaporated to dryness and the products isolated by chromatogra-
anol (0.5 mL). After a further 15 min stirring, the mixture was con-
centrated. After flash chromatography with PE/EA, 10:1, the prod-
uct was directly converted into 10. Colourless solid, C51H70O4Si
(mol. mass 775.185 g/mol), m.p. 77.4 °C, [α]2D0 ϭ Ϫ38.7 (c ϭ 1,
CHCl3). TLC (PE/EA, 10:1): Rf ϭ 0.30 (UV, H2SO4). 1H NMR
(400 MHz, CDCl3):
δ ϭ 7.70Ϫ7.62 (m, 4 H, o-SiPh2tBu),
7.44Ϫ7.31 (m, 6 H, m/p-SiPh2tBu), 7.23, 6.88 (2 ϫ m ഠ d, 2 ϫ 2
H, CH3OC6H4CH2O, 3J ϭ 11.2 Hz), 5.12 (br. d, 1 H, H-6, 3J6,7a ϭ
5.1 Hz), 4.42, 4.40 (2 ϫ d, 2 ϫ 1 H, CH3OC6H4CH2O, 3J ϭ
11.7 Hz), 4.27 (m, 1 H, H-16), 3.79 (s, 3 H, CH3OC6H4CH2O),
3.51 (m, 1 H, H-3),3.33Ϫ3.26 (m, 2 H, H-22, H-26a), 3.22 (dd, 1
3
H, H-26b, J25,26b ϭ 6.6, 9.2 Hz), 2.33, 2.14 (2 ϫ m, 2 ϫ 2 H, H-
4a, H-4b), 1.04 (s, 9 H, tBuPh2Si), 0.99, 0.77 (je s, je 3 H, CH3-
phy. For small-scale reactions, a suitable amount of silica gel was 18, -19), 0.96 (d, 3 H, CH3-21, 3J21,20 ϭ 6.4 Hz), 0.91 (d, 3 H, CH3-
3
added, the mixtures evaporated to dryness, and the so-obtained
powders poured directly onto pre-packed columns of silica gel and
purified by chromatography.
27, J27,25 ϭ 6.6 Hz), 2.00Ϫ0.72 (m, steroid H) ppm. 13C NMR
(125.77 MHz, CDCl3): δ ϭ 159.44, 131.30 (CH3OCC4H4CCH2O),
141.70 (C-5), 136.16 (o-SiPh2tBu), 135.23 (q-SiPh2tBu), 129.83,
129.52 (p-SiPh2tBu), 129.80, 114.11 (CH3OCC4H4CCH2O),
127.85Ϫ127.82 (m-SiPh2tBu), 121.29 (C-6), 90.73 (C-22), 83.54 (C-
16), 76.05 (C-26), 73.60 (C-3), 73.05 (CH3OC6H4CH2O), 55.65
(CH3OC6H4CH2O), 42.85 (C-4), 41.06, 37.00 (C-10, C-13), 27.39
[(CH3)CSi], 19.81, 16.79 (CH3-18, -19), 19.53 (CH3-21), 19.40
[(CH3)CSi], 17.46 (CH3-27), 39.85, 37.60, 32.37, 32.25, 31.96, 21.03
(CH2-1, -2, -4, -7, -11, -12, -15, -23, -24) 64.44, 57.37, 50.43, 30.97,
38.26, 34.13 (CH-8, -9, -14, -17, -20, -25) ppm.
(22R,25R)-3β-O-tert-Butyldiphenylsilyloxy-26-hydroxy-5-furosten
(8): Lithium aluminium hydride (877 mg, 23.0 mmol) was placed
into a 500-mL three-neck round-bottomed flask, equipped with
condenser, dropping funnel and N2-tap, and dissolved in anhydrous
diethyl ether (100 mL) under argon. AlCl3 (12.32 g, 92 mmol) was
dissolved in anhydrous diethyl ether (100 mL), added cautiously
(vigorous reaction!) to the first solution dropwise and the mixture
stirred for 30 min at room temperature. 7[13] (1.509 g, 2.31 mmol)
was dissolved in anhydrous diethyl ether (100 mL) and added (22R,25R)-3β-Hydroxy-26-p-methoxybenzyloxy-5-furosten
(10):
through another dropping funnel. The reaction was monitored by
TLC, and quenched by the addition of water (50 mL). 2  hydro-
chloric acid (100 mL) was added and the ether phase was sepa-
Compound 9 (see above) was dissolved in wet THF (20 mL) in a
50 mL round-bottomed flask, and a 1  solution of tetrabutylam-
monium fluoride in THF (400 µL) was added. After 3 days stirring
rated. The aqueous phase was extracted four times with diethyl at room temperature, an acceptable conversion was determined by
ether (200 mL). The combined ether phases were washed three TLC (PE/EA, 3:1). The reaction solvents were evaporated and the
times with sodium hydrogen carbonate solution (200 mL) and dried residue wastaken up in ethyl acetate and washed once with satu-
over sodium sulfate. After flash chromatography, compound 8
rated sodium hydrogen carbonate solution and once with NaCl
solution. After drying over MgSO4, filtration, evaporation and
flash chromatography with PE/EA, 5:1, compound 10 (132 mg,
0.25 mmol, 30% over two steps) was obtained. Colourless solid,
(718 mg, 1.10 mmol, 47%) was obtained. Colourless solid,
C43H62O3Si (mol. mass 655.036 g/mol), m.p. 63.5Ϫ64.1 °C, [α]D20
ϭ
Ϫ46.5 (c ϭ 1, CHCl3), TLC (PE/EA, 3:1): Rf ϭ 0.22, (PE/EA,
1
10:1): Rf ϭ 0.07 (UV, H2SO4). H NMR (400 MHz, CDCl3): δ ϭ C35H52O4 (mol. mass 536.785 g/mol), m.p. 82.7Ϫ82.9 °C, [α]D20
ϭ
7.70Ϫ7.63 (m, 4 H, o-SiPh2tBu), 7.45Ϫ7.32 (m, 6 H, m/p-
SiPh2tBu), 5.11 (br. d, 1 H, H-6, 3J6,7a ϭ 4.8 Hz), 4.28 (m, 1 H, H-
16), 3.57Ϫ3.40 (m, 3 H, H-3, H-26a, H-26b), 3.31 (m, 1H H-22),
Ϫ37.6 (c ϭ 0.2, CHCl3). TLC (PE/EA, 3:1): Rf ϭ 0.14 (UV,
H2SO4). 1H NMR (400 MHz, CDCl3): δ ϭ 7.25, 6.86 (2 ϫ m, 2 ϫ
3
2 H, CH3OC6H4CH2O), 5.34 (br. d, 1 H, H-6, J6,7a ϭ 5.5 Hz),
3
2.33 (m, 2 H, H-4), 1.08 (s, 9 H, tBuPh2Si), 1.00, 0.78 (je s, je 3 H, 4.44, 4.40 (2 ϫ d, 2 ϫ 1 H, CH3OC6H4CH2O, J ϭ 11.7 Hz), 4.29
3
3
CH3-18, CH3-19), 0.98 (d, 3 H, CH3-21, J21,20 ϭ 6.4 Hz), 0.92 (d, (ddd ഠ dt, 1 H, H-16, J ϭ 5.1, 7.7 Hz), 3.80 (s, 3 H, CH3OC6H4-
3 H, CH3-27, 3J27,25 ϭ 6.6 Hz), 2.02Ϫ1.04 (m, steroid H) ppm. 13
C
CH2O), 3.51 (m, 1 H, H-3), 3.33Ϫ3.26 (m, 2 H, H-22, H-26a), 3.22
3
NMR (100.67 MHz, CDCl3): δ ϭ 141.29 (C-5), 135.77 (o-
SiPh2tBu), 134.82, 134.76 (q-SiPh2tBu), 129.45, 129.41 (p-
(dd, 1 H, H-26b, J25,26b ϭ 6.8, 9.0 Hz), 1.02, 0.80 (je s, je 3 H,
CH3-18, -19), 0.98 (d, 3 H, CH3-21, 3J21,20 ϭ 6.6 Hz), 0.92 (d, 3 H,
SiPh2tBu), 127.46Ϫ127.43 (m-SiPh2tBu), 120.88 (C-6), 90.34 (C- CH3-27, J27,25 ϭ 6.4 Hz), 2.27Ϫ0.82 (m, steroid H) ppm. 13C
22), 83.23 (C-16), 73.19 (C-3), 68.05 (C-26), 37.90 (C-20), 40.67, NMR (100.67 MHz, CDCl3): δ ϭ 158.99, 130.92 (CH3OCC4H4C-
36.60 (C-10, C-13), 27.00 [(CH3)CSi], 19.43 [(CH3)CSi], 19.13, CH2O), 140.80 (C-5), 129.15, 113.77 (CH3OCC4H4CCH2O), 121.49
3
18.90, 16.61, 16.42 (CH3-18, -19, -21, -27), 32.20, 31.96, 31.85,
31.72, 30.63 30.41, 30.11, 20.63 (CH2-1, -2, -4, -7, -11, -12, -15,
(C-6), 90.47 (C-22), 83.29 (C-16), 75.81 (C-26), 72.82 (C-3), 71.88
(CH3OC6H4CH2O), 55.46 (CH3OC6H4CH2O), 42.52 (C-4), 40.93,
4006
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2003, 4003Ϫ4011

Synthesis of Dihydrodiosgenin Glycosides
FULL PAPER
36.87 (C-10, C-13) 19.71, 16.73 (CH3-18, -19), 19.33 (CH3-21), -14, -17, -20, -25), 39.80, 37.29, 32.70, 32.32, 31.61, 30.77, 28.25,
17.38 (CH3-27), 39.71, 38.14, 32.53, 32.27, 31.89, 31.26, 31.01, 21.02 (CH2-1, -2, -7, -11, -12, -15, -23, -24), Ϫ5.17, Ϫ5.19 (tBu-
21.00 (CH2-1, -2, -7, -11, -12, -15, -23, -24) 65.40, 57.18, 50.33, Me2Si) ppm.
37.51, 31.87, 34.00 (CH-8, -9, -14, -17, -20, -25) ppm.
14: Colourless solid, C33H58O3Si (mol. mass 530.897 g/mol), m.p.
(22R,25R)-3β-O-Acetyldihydrodiosgenin, 3β-Acetoxy-26-hydroxy-5- 77.5 °C, [α]2D0 ϭ Ϫ45.6 (c ϭ 0.5, CHCl3). TLC (toluene/acetone,
furosten (12): 3β-O-Acetyldiosgenin (11, 3.24 g, 70.9 mmol) was
1
10:1): Rf ϭ 0.24 (H2SO4). H NMR (400 MHz, CDCl3): δ ϭ 5.35
suspended in glacial acetic acid (50 mL) in a 100 mL round-bot-
tomed flask. NaBH3CN (579 mg, 92.2 mmol) was added cautiously 2 H, H-3, H-26a), 3.37 (dd, 1 H, H-26b, J25,26b ϭ 6.5, J26a,b
(br. d, 1 H, H-6, J ϭ 4.7 Hz), 4.30 (m, 1 H, H-16), 3.55Ϫ3.42 (m,
3
ϭ
(gas production!). The reaction was monitored by TLC with tolu-
ene/acetone, 10:1 [Rf (11) ϭ 0.80]. After 24 h of stirring at room
temperature, the reaction mixture was cautiously neutralized with
saturated Na2CO3 solution and extracted three times with dichloro-
methane. The organic phase was dried over magnesium sulfate and
9.6 Hz), 3.31 (m, 1 H, H-22), 2.33Ϫ2.19 (m, 2 H, H-4a, H-4b),
1.03, 0.81 (je s, je 3 H, CH3-18, -19), 0.99 (d, 3 H, CH3-21, 3J21,20 ϭ
6.5 Hz), 0.88 (m, 12 H, tBuMe2Si, CH3-27), 0.03 (s, 6 H, tBu-
Me2Si), 2.04Ϫ0.86 (m, steroid-H) ppm. 13C NMR (100.67 MHz,
CDCl3): δ ϭ 140.94 (C-5), 121.63 (C-6), 90.57 (C-22), 83.44 (C-
the solvents evaporated. After flash chromatography with toluene/ 16), 71.90 (C-3), 68.33 (C-26), 42.43 (C-4), 38.07 (C-20), 36.13 (C-
acetone, 10:1, compound 12 (2.43 g, 5.29 mmol, 75%) was ob-
25), 40.85, 36.78 (C-10, C-13), 26.11 [(CH3)3CSi], 19.56, 16.58
(CH3-18, -19), 19.23 (CH3-21), 18.51 [(CH3)3CSi], 16.88 (CH3-27),
tained. Colourless solid, C29H46O4 (mol. mass 458.673 g/mol), m.p.
108.3Ϫ108.6 °C, [α]D20 ϭ Ϫ57.3 (c ϭ 0.7, CHCl3), ref.[12] (no data 39.63, 37.42, 32.43, 32.17, 31.22, 30.58, 30.28, 20.86 (CH2-1, -2,
1
given). TLC (toluene/acetone, 10:1): Rf ϭ 0.20 (H2SO4). H NMR
-7, -11, -12, -15, -23, -24) 65.46, 57.14, 50.28, 32.12 (CH-8, -9, -14,
(400 MHz, CDCl3): δ ϭ 5.37 (br. d, 1 H, H-6, J ϭ 4.1 Hz), 4.60 -17), Ϫ5.19, Ϫ5.21 (tBuMe2Si) ppm.
3
(m, 1 H, H-3), 4.31 (ddd ഠ q, 1 H, H-16, J ϭ 7.6, 5.4 Hz), 3.50
(22R,25R)-3β-(2,3,4-Tri-O-benzoyl-α-L-rhamnopyranosyloxy)-26-
3
(dd, 1 H, H-26a, J25,26a ϭ 6.3, J26a,b ϭ 10.7 Hz), 3.45 (dd, 1 H,
(2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyloxy)-5-furosten (16): Con-
H-26b, J25,26b ϭ 6.0, 3J26a,b ϭ 10.7), 3.33 (ddd ഠ dt, 1H H-22, 3J ϭ
3.8, 8.2 Hz), 2.35Ϫ2.29 (m, 2 H, H-4a, H-4b), 2.03 (s, 3 H,
CH3COO), 1.03, 0.81 (je s, je 3 H, CH3-18, -19), 1.00 (d, 3 H,
version following GP: 5[11,12] (70 mg, 0.17 mmol), 15 (219 mg,
0.42 mmol), argon, fresh anhydrous diethyl ether (80 mL), freshly
˚
activated 4-A mol. sieves, 80 min, room temperature, DMTST
3
3
CH3-21, J21,20 ϭ 6.9 Hz), 0.92 (d, 3 H, CH3-27, J27,25 ϭ 6.6 Hz),
2.02Ϫ0.90 (m, steroid H) ppm. 13C NMR (100.67 MHz, CDCl3):
δ ϭ 170.68 (CH3COO), 139.83 (C-5), 122.53 (C-6), 90.51 (C-22),
83.37 (C-16), 74.04 (C-3), 68.22 (C-26), 38.24 (C-4), 38.07 (C-20),
35.86 (C-25), 40.85, 36.85 (C-10, C-13), 21.56 (CH3COO), 19.46,
16.58 (CH3-18, -19), 19.04 (CH3-21), 16.77 (CH3-27), 39.55, 37.14,
32.36, 31.71, 30.58, 30.29, 27.89, 20.79 (CH2-1, -2, -7, -11, -12,
-15, -23, -24) 65.24, 57.04, 50.15, 32.12 (CH-8, -9, -14, -17) ppm.
(325 mg, 1.26 mmol), 6 h. TLC with PE/EA, 3:1 [Rf (15) ϭ 0.41]
and PE/EA, 1:1 [Rf (5) ϭ 0.04, Rf (15) ϭ 0.81, Rf (monorhamnosyl-
ated) ϭ 0.22, 0.28]. Triethylamine (1 mL), 10 min, filtration
through Celite, evaporation to dryness, three times co-distillation
with toluene. After flash chromatography with PE/EA, 8:1 Ǟ 5:1,
16 (149 mg, 0.11 mmol, 66%) was obtained. Colourless solid,
C81H88O17 (mol. mass 1333.555 g/mol). TLC (PE/EA, 1:1): Rf ϭ
1
0.89, (PE/EA, 3:1): Rf ϭ 0.23 (UV, H2SO4). H NMR (500 MHz,
(22R,25R)-3β-Acetoxy-26-O-tert-butyldimethylsilyloxy-5- C6D6): δ ϭ 8.33Ϫ8.27, 8.09Ϫ7.98, 7.11Ϫ6.72 (m, 30 H, 6 ϫ Bz),
3
3
furosten (13),
(22R,25R)-26-O-tert-Butyldimethylsilyloxy-3β-hy-
6.45 (dd, 1 H, H-3Ј, J2Ј,3Ј ϭ 3.6, J3Ј,4Ј ϭ 10.2 Hz), 6.36 (dd, 1 H,
3
3
droxy-5-furosten (14): Compound 12 (1.59 g, 3.46 mmol) was dis-
solved in anhydrous pyridine (30 mL) under argon in a 100 mL
round-bottomed flask and cooled in an ice bath. tert-Butyldimeth-
H-3ЈЈ, J2ЈЈ,3ЈЈ ϭ 3.5, J3ЈЈ,4ЈЈ ϭ 10.3 Hz), 6.32Ϫ6.21 (m, 2 H, H-4Ј,
H-4ЈЈ), 6.20 (dd, 1 H, H-2Ј, 3J1Ј,2Ј ϭ 1.8, 3J2Ј,3Ј ϭ 3.3 Hz), 6.17 (dd,
3
3
1 H, H-2ЈЈ, J1ЈЈ,2ЈЈ ϭ 1.8, J2ЈЈ,3ЈЈ ϭ 3.3 Hz), 5.31 (d, 1 H, H-1Ј,
ylchlorosilane (626 mg, 4.15 mmol) was added. The mixture was 3J1Ј,2Ј ϭ 1.3 Hz), 5.25 (br. d, 1 H, H-6, J ϭ 5.3 Hz), 5.03 (d, 1 H,
stirred for 24 h, and monitored by TLC with toluene/acetone, 10:1
H-1ЈЈ, 3J1ЈЈ,2ЈЈ ϭ 1.5 Hz), 4.55 (m, 1 H, H-5Ј), 4.43 (m, 1 H, H-5ЈЈ),
[Rf (12) ϭ 0.20). For work-up, methanol (0.5 mL) was added, 4.35 (ddd ഠ m, 1 H, H-16), 3.56 (m, 1 H, H-3), 3.52 (dd, 1 H, H-
3
2
3
whereupon the product crystallised. The so-obtained crude 13 was
26a, J25,26a ϭ 6.9, J26a,26b ϭ 9.4 Hz), 3.43 (ddd, 1 H, H-22, J ϭ
3
2
dissolved in dichloromethane (5 mL) and methanol (5 mL). The 2.6, 7.9, 8.1 Hz), 3.23 (dd, 1 H, H-26b, J25,26b ϭ 5.9, J26a,26b
ϭ
pH was raised to 9.5 by adding solid sodium methoxide, and the
reaction mixture was stirred for 16 h at room temperature. Neutral-
isation was carried out by treatment with Amberlite IR 120 (Hϩ).
9.4 Hz), 2.40 (m, 1 H), 2.31 (m, 1 H), 2.05Ϫ1.00 (m, steroid H),
3
3
1.45 (d, 3 H, H-6ЈЈ, J5ЈЈ,6ЈЈ ϭ 6.4 Hz), 1.43 (d, 3 H, H-6Ј, J5Ј,6Ј
ϭ
6.4 Hz), 0.99Ϫ0.89 (m, CH3-18, -19, -21, -27) ppm. 13C NMR
After flash chromatography with toluene/acetone, 10:1, 14 (1.77 g, (100.61 MHz, CDCl3): δ ϭ 166.61Ϫ166.11 (C6H5COO), 140.51 (C-
3.33 mmol, 96%) was obtained.
5), 133.61, 133.43, 133.18, 130.54, 130.44, 130.36, 130.29, 130.25,
130.21, 129.07, 128.88, 128.66 (C6H5COO), 122.52 (C-6), 98.64 (C-
1ЈЈ), 96.92 (C-1Ј), 90.51 (C-22), 83.75 (C-16), 78.70 (C-3), 74.24 (C-
26), 72.99, 72.88 (C-4Ј, C-4ЈЈ), 72.44 (C-2Ј), 71.88 (C-2ЈЈ), 71.18 (C-
3Ј, C-3ЈЈ), 67.72, 67.67 (C-5Ј, C-5ЈЈ), 66.06 (C-17), 57.53 (C-14),
50.83 (C-9), 38.57, 33.74 (C-8, C-20), 40.12, 39.02, 37.85, 32.95,
32.61, 32.10, 31.45, 31.15, 30.09, 21.38, 20.77 (C-10, C-13, CH2-1,
Ϫ2, -4, -7, -11, -12, -15, -23, -24, -25), 18.30, 18.19 (C-6Ј, C-6ЈЈ),
19.72, 19.43, 17.50, 16.95 (CH3-18, -19, -21, -27) ppm.
13: Colourless solid. C35H60O4Si (572.934): calcd. C 73.37, H 10.56;
found C 72.72, H 10.63. M.p. 68.1Ϫ68.7 °C, [α]2D0 ϭ Ϫ53.7 (c ϭ
0.6, CHCl3). TLC (toluene/acetone, 10:1): Rf ϭ 0.86 (H2SO4). H
1
NMR (500 MHz, C6D6): δ ϭ 5.29 (br. d, 1 H, H-6, J ϭ 5.0 Hz),
4.84 (m, 1 H, H-3), 4.30 (m, 1 H, H-16), 3.48 (dd, 1 H, H-26a,
2
3J25,26a ϭ 5.5, J26a,26b ϭ 9.6 Hz), 3.45Ϫ3.37 (m, 2 H, H-26b, H-
22), 2.49 (m, 1 H, H-4a), 2.37 (m, 1 H, H-4b), 1.97 (m, 1 H), 1.88
(m, 1 H), 1.84Ϫ0.86 (m, steroid H), 1.76 (s, 3 H, CH3COO), 1.00
(s, 9 H, tBuMe2Si), 0.99Ϫ0.96, 0.89Ϫ0.86 (2 ϫ m, 2 ϫ 6 H, CH3-
18, -19, -21, -27), 0.08 (s, 6 H, tBuMe2Si) ppm. 13C NMR
(22R,25R)-3β-(2,3,4-Tri-O-benzoyl-α-
L-rhamnopyranosyloxy)-26-
tert-butyldimethylsilyloxy-5-furosten (17): Conversion following
(100.61 MHz, C6D6): δ ϭ 169.64 (CH3COO), 139.79 (C-5), 122.77 GP: 14 (200 mg, 0.38 mmol), 15 (255 mg, 0.49 mmol), argon, fresh
˚
(C-6), 90.53 (C-22), 83.43 (C-16), 73.94 (C-3), 68.49 (C-26), 38.67
anhydrous diethyl ether (80 mL), freshly activated 4-A mol. sieves,
(C-4), 40.90, 36.92 (C-10, C-13), 26.23 [(CH3)3CSi], 21.04 75 min, room temperature, DMTST (379 mg, 1.47 mmol), 5.5 h.
(CH3COO), 19.33, 19.22, 17.06, 16.65 (CH3-18, -19, -21, -27), 18.59 TLC with PE/EA, 3:1 [Rf (14) ϭ 0.29, Rf (15) ϭ 0.41] and PE/EA,
[(CH3)3CSi], 65.82, 57.18, 50.36, 38.42, 36.28, 31.88 (CH-8, -9,
1:1 [Rf (14) ϭ 0.35, Rf (15) ϭ 0.81]. Triethylamine (0.5 mL), 10 min,
Eur. J. Org. Chem. 2003, 4003Ϫ4011
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4007

R. Suhr, M. Lahmann, S. Oscarson, J. Thiem
FULL PAPER
filtration through Celite, evaporation to dryness, three times co-
distillation with toluene. After flash chromatography with PE/EA, freshly activated 4-A mol. sieves, room temperature, 1 h, DMTST
1.30 mmol), argon, anhydrous diethyl ether (40 mL), a spatula of
˚
6:1, 17 (137 mg, 0.14 mmol, 36%) and a mixture of 15 and 17
(90 mg) were obtained.
(1.01 g, 3.90 mmol), room temperature, TLC was carried out using
toluene/EA, 6:1 [Rf (21) ϭ 0, Rf (15) ϭ 0.68] and PE/EA, 2:1
[Rf (21)ϭ 0, Rf (15) ϭ 0.62], 16 h, triethylamine (2 mL), room tem-
perature, 15 min, filtration through Celite, evaporation, flash chro-
matography with PE/EA, 2:1. The so-obtained product was dis-
solved in pyridine (5 mL) and after cooling in an ice-bath, acetic
acid anhydride (3 mL) was added. The reaction mixture was stirred
at room temperature for 4 days. After evaporation and column
chromatography with PE/toluene/EA, 4:1:1, compound 22 (379 mg,
0.26 mmol, 60%) was obtained. Needles. C85H82O21Si (1467.634):
calcd. C 69.56, H 5.63; found C 69.96, H 5.62. M.p. 108.0Ϫ108.7
°C, [α]2D0 ϭ ϩ90.9 (c ϭ 0.7, CHCl3). TLC (toluene/EA, 6:1): Rf ϭ
0.62 (UV, H2SO4), (PE/EA, 2:1): Rf ϭ 0.39 (UV, H2SO4). 1H NMR
(400 MHz, CDCl3): δ ϭ 8.16Ϫ8.11 (m, 2 H, Ar), 7.98Ϫ7.92 (m, 4
H, Ar), 7.88Ϫ7.82 (m, 2 H, Ar), 7.79Ϫ7.74 (m, 4 H, Ar), 7.72Ϫ7.68
(m, 2 H, Ar), 7.58Ϫ6.97 (m, 31 H, Ar), 5.94 (dd, 1 H, H-3Ј, 3J2,3 ϭ
17: Colourless crystals. C60H80O10Si (989.357): calcd. C 72.84, H
8.15; found C 72.08, H 8.19. M.p. 82 °C, [α]2D0 ϭ ϩ33.9 (c ϭ 0.5,
CHCl3). TLC (PE/EA, 1:1): Rf ϭ 0.94, (PE/EA, 3:1): Rf ϭ 0.36
1
(UV, H2SO4). H NMR (500 MHz, C6D6): δ ϭ 8.32, 8.07, 8.04 (3
3
ϫ d, 3 ϫ 2 H, 3 ϫ o-C6H5COO, J ϭ 7.3, 7.3, 7.6 Hz), 7.10Ϫ6.72
(m, 9 H, 3 ϫ C6H5COO), 6.45 (dd, 1 H, H-3Ј, 3J2Ј,3Ј ϭ 3.2, 3J3Ј,4Ј
ϭ
3
3
10.1 Hz), 6.29 (dd ഠ t, 1 H, H-4Ј, J3Ј,4Ј ϭ 10.1, J4Ј,5Ј ϭ 9.8 Hz),
3
3
6.20 (dd, 1 H, H-2Ј, J1Ј,2Ј ϭ 1.2, J2Ј,3Ј ϭ 3.2 Hz), 5.31 (d ഠ br. s,
1 H, H-1Ј), 5.26 (m, 1 H, H-6), 4.56 (m, 1 H, H-5Ј), 4.31 (m, 1 H,
H-16), 3.56 (m, 1 H, H-3), 3.51Ϫ3.26 (m, 3 H, H-26a, H-22, H-
26b), 2.40, 2.30 (2 ϫ m, 2 ϫ 1 H, H-4a, H-4b), 2.05Ϫ0.83 (m,
3
steroid H), 1.43 (d, 3 H, H-6Ј, J5Ј,6Ј ϭ 6.3 Hz), 1.03Ϫ0.84 (m,
CH3-18, -19, -21, -27, tBuMe2Si), 0.08, Ϫ0.01 (2 ϫ s, 2 ϫ 3 H,
tBuMe2Si) ppm.
3
3
3
3.3, J3,4 ϭ 10.3 Hz), 5.84 (dd, 1 H, H-2Ј, J1,2 ϭ 1.7, J2,3
3.1 Hz), 5.78 (dd, 1 H, H-3ЈЈ, J2,3 ϭ 3.1, J3,4 ϭ 10.3 Hz),
5.74Ϫ5.61 (m, 4 H, H-1**, H-2ЈЈ, H-4Ј, H-4ЈЈ), 5.35 (d, 1 H, H-1*
ϭ
3
3
(22R,25R)-26-(2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranosyloxy)-3β-
acetoxy-5-furosten (19): Conversion following GP: 12 (100 mg,
0.21 mmol), 29 (153 mg, 0.24 mmol), argon, fresh anhydrous
3
2
, J1,2 ϭ 1.8 Hz), 5.06 (d, 1 H, C6H5CH2O-a, J ϭ 11.0 Hz), 5.00
3
3
˚
(dd ഠ t, 1 H, H-4, J3,4 ϭ 8.8, J4,5 ϭ 9.5 Hz), 4.75 (d, 1 H,
CH2Cl2 (80 mL), 1 spatula of freshly activated 4-A mol. sieves, 1 h,
C6H5CH2O-b, 2J ϭ 11.0 Hz), 4.72 (m, 1 H, H-5Ј), 4.68 (d, 1 H, H-
room temperature, DMTST (204 mg, 0.79 mmol), 4.5 h. TLC was
carried out using toluene/acetone, 20:1 [Rf (12) ϭ 0.06, Rf (29) ϭ
0.59]. Triethylamine (0.5 mL), 15 min. Evaporation was carried out
in the presence of silica gel, and the so-obtained powdery mixture
was poured onto a column of silica gel pre-packed with PE and
directly chromatographed with PE/EA, 4:1. Compound 19 (40 mg,
0.04 mmol, 18%) was obtained. Slightly yellow solid. C63H72O13
(1037.238): calcd. C 72.95, H 7.00; found C 72.81, H 7.43. M.p.
159.5Ϫ159.8 °C, [α]2D0 ϭ Ϫ11.8 (c ϭ 0.4, CHCl3). TLC (toluene/
acetone, 20:1): Rf ϭ 0.37, (UV, H2SO4). 1H NMR (400 MHz,
CDCl3): δ ϭ 8.19, 8.15, 8.05, 7.96 (4 ϫ d, 4 ϫ 2 H, 4 ϫ o-
C6H5COO, 3J ϭ 7.9, 7.6, 7.8, 7.6 Hz), (m, 12 H, 4 ϫ m/p-
C6H5COO), 6.19 (dd ഠ t, 1 H, H-3Ј, 3J2Ј,3Ј ϭ 9.5, 3J3Ј,4Ј ϭ 9.8 Hz),
5.96Ϫ5.86 (m, 2 H, H-2Ј, H-4Ј), 5.29 (br. d, 1 H, H-6, J ϭ 4.7 Hz),
3
1, J1,2 ϭ 7.3 Hz), 4.23Ϫ4.13 (m, 2 H, H-3, H-5ЈЈ), 4.09 (dd ഠ t, 1
H, H-2, J1,2 ϭ 8.1, J2,3 ϭ 8.4 Hz), 3.88 (dd, 1 H, H-6a, J5,6a
7.0, J6a,6b ϭ 11.4 Hz), 3.74 (dd, 1 H, H-6b, J5,6a ϭ 2.2, J6a,6b
11.7 Hz), 3.51 (ddd, 1 H, H-5, J5,4 ϭ 9.5, J5,6a ϭ 7.0, J5,6b
3
3
3
ϭ
ϭ
ϭ
ϭ
2
3
2
3
3
3
3
2.2 Hz), 1.95 (s, 3 H, CH3COO), 1.28 (d, 3 H, H-6ЈЈ, J5,6
6.2 Hz), 1.15 (s, 9 H, tBuPh2Si), 1.11 (d, 3 H, H-6Ј, 3J5,6 ϭ 6.2 Hz)
ppm. 13C NMR (100.67 MHz, CDCl3): δ ϭ 169.94 (CH3COO),
165.72, 165.68, 165.38, 165.23, 165.21, 164.85 (6 ϫ C6H5COO),
137.83, 136.54, 135.65, 135.61, 133.35Ϫ133.12, 132.76Ϫ132.39,
130.00Ϫ127.74, 125.31 (C6H5CH2O, 6 ϫ C6H5COO, tBuPh2Si),
99.89 (C-1), 99.32 (C-1*), 98.05 (C-1**), 85.63 (C-5ЈЈ), 76.76 (C-2),
75.56 (C-5), 72.36, 72.08, 71.97 (C-2ЈЈ, C-4Ј, C-4ЈЈ), 71.18 (C-4),
70.98 (C-2Ј, C6H5CH2O), 70.06 (C-3Ј), 69.08 (C-3ЈЈ), 68.04 (C-3),
67.31 (C-5Ј), 3.72 (C-6), 27.06 [(CH3)3CSi], 21.72 (CH3COO), 19.55
[(CH3)3CSi], 17.45, 17.38 (C-6Ј, C-6ЈЈ) ppm.
3
2
4.85 (m, 1 H, H-3), 4.64 (dd, 1 H, H-6Јa, J5Ј,6Јa ϭ 3.3, J6Јa,6Јb
ϭ
3
12.0 Hz), 4.58 (d, 1 H, H-1Ј, J1Ј,2Ј ϭ 7.9 Hz), 4.51 (dd, 1 H, H-
6Јb, J5Ј,6Јb ϭ 5.0, J6Јa,6Јb ϭ 12.0 Hz), 4.31 (m, 1 H, H-16),
3.79Ϫ3.73 (m, 2 H, H-26a, H-5Ј), 3.27 (dd, 1 H, H-26b, J25,26b
3
2
Ethyl 2,4-Di-O-benzoyl-3,6-di-O-tert-butyldimethylsilyl-1-thio-β-D-
ϭ
glucopyranoside (25): Compound 23[16,28] (1.65 g, 4.20 mmol) was
dissolved in anhydrous methanol (30 mL) and the pH was raised
to 9.5 by adding a 1  solution of NaOMe in methanol. After
stirring at room temperature for 2 h, the solution was neutralized
with Dowex 50 WX8 (Hϩ) resin. The resin was filtered off, the
mixture was evaporated to dryness and the crude product was co-
distilled three times with toluene. The so-obtained crude product
was dissolved in anhydrous DMF (4.2 mL), and triethylamine
(1.4 mL, 10.08 mmol) and DMAP (42 mg, 0.4 mmol) were added.
The solution was stirred while tert-butylchlorodimethylsilane
(1.392 g, 9.24 mmol) in anhydrous DMF (4.2 mL) was added drop-
wise. After stirring at room temperature for 24 h, TLC: PE/EA, 4:1
[Rf (23) ϭ 0, Rf (products) ϭ 0.30, 0.59, 0.86], another portion of
tert-butylchlorodimethylsilane (348 mg, 2.31 mmol) in anhydrous
DMF (1 mL) was added dropwise. Stirring continued for 24 h at
room temperature. The reaction solvents were evaporated under
reduced pressure at 30 °C, and the resulting residue was dissolved
in dichloromethane, washed with 10% NH4Cl solution and with
water and dried over sodium sulfate. A suitable amount of silica
gel was added and concentration gave a powdery mixture, which
3
7.0, J26a,b ϭ 8.5 Hz), 3.18 (m, 1 H, H-22), 2.50 (m ഠ dd, 1 H, H-
3
2
3
4β, J3,4β ϭ 3.2, J4α,4β ϭ 12.9 Hz), 2.29 (ddd, 1 H, H-4α, J3,4α
ϭ
11.0, J4α,4β ϭ 13.2, 4J4α,6 ϭ 2.2 Hz), 1.96 (m, 1 H), 1.88 (m, 1 H),
1.81 (m, 1 H), 1.76 (s, 3 H, CH3COO), 0.89 (d, 3 H, CH3-21,
3J20,21 ϭ 9.2 Hz), 0.88 (s, 3 H, CH3-19), 0.84 (s, 3 H, CH3-18), 0.81
2
3
(d, 3 H, CH3-27, J25,27 ϭ 6.9 Hz), 1.74Ϫ0.78 (m, steroid H) ppm.
13C NMR (100.67 MHz, CDCl3): δ ϭ 169.64 (CH3COO), 166.28,
166.05, 165.46, 165.23 (4 ϫ C6H5COO), 139.80 (C-5), 133.25,
133.12, 133.02, 132.96 (4 ϫ p-C6H5COO), 130.54, 130.31, 129.73,
129.47 (4 ϫ q-C6H5COO), 130.13Ϫ130.03 (4 ϫ o-C6H5COO),
128.58Ϫ128.34 (4 ϫ m-C6H5COO), 122.77 (C-6), 101.88 (C-1Ј),
90.39 (C-22), 83.35 (C-16), 75.17 (C-26), 73.94 (C-3), 73.72 (C-3Ј),
72.67 (C-5Ј), 72.51 (C-2Ј), 70.64 (C-4Ј), 65.78 (C-17), 63.50 (C-6Ј),
57.21 (C-14), 50.37 (C-9), 40.87, 36.91 (C-10, C-13), 38.68 (C-4),
38.38 (C-20), 33.77 (C-25), 31.86 (C-8), 21.04 (CH3COO), 19.34,
19.15 (CH3-19, -21), 16.90, 16.61 (CH3-18, -27), 39.78, 37.27, 32.70,
32.33, 31.26, 30.85, 28.25, 21.01 (CH2-1, -2, -7, -11, -12, -15, -23,
-24) ppm.
Benzyl 4-O-Acetyl-6-O-tert-butyldiphenylsilyl-(2,3,4-tri-O-benzoyl-
α-
pyranosyl)-(1Ǟ3)-β-
GP: Acceptor 21 (220 mg, 0.43 mmol), donor 15 (668 mg,
L
-rhamnopyranosyl)-(1Ǟ2)-(2,3,4-tri-O-benzoyl-α-
L-rhamno- was added to a PE pre-packed column of silica gel and chromato-
D-glucopyranoside (22): Conversion following
graphed with PE/EA, 1:0 Ǟ 4:1. Three fractions were obtained.
F1: 2,3,6-trisilylated (260 mg, 0.46 mmol, 11%, Rf ϭ 0.86); F2: 3,6-
4008
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4003Ϫ4011

Synthesis of Dihydrodiosgenin Glycosides
disilylated (341 mg, 0.75 mmol, 18%, Rf ϭ 0.59); F3: 2,6- and 4,6- furosten (28): Compound 26 (94 mg, 0.08 mmol) was dissolved in
FULL PAPER
disilylated compounds (517 mg, 1.14 mmol, 27%, Rf ϭ 0.30), as
proven after benzoylation by H NMR in the next step. The frac-
tion F2 (341 mg, 0.75 mmol) was dissolved in anhydrous pyridine
(5 mL), and after cooling in an ice bath, benzoyl chloride (0.19 mL,
a mixture of anhydrous methanol (4 mL) and anhydrous CHCl3
(5 mL). Sodium methoxide was added until pH 8.5 was reached,
whereupon no reaction occurred within 48 h. The pH was raised
to 10Ϫ12, and the reaction mixture was stirred for a further 48 h.
1
1.65 mmol) and DMAP (3 mg) were added. The reaction was TLC: PE/EA, 4:1 [Rf (26) ϭ 0.76, Rf (27) ϭ 0.50]. The solvent was
stirred at room temperature for 5 days with addition of benzoyl
chloride (0.05 mL and 0.10 mL) after 3 and 4 days, respectively.
The reaction mixture was dissolved in toluene (30 mL), washed
three times with water and once with saturated NaCl solution,
dried over MgSO4, filtered and evaporated to dryness. After flash
chromatography with PE/toluene/EA, 4:1:0 Ǟ 4:1:1, a mixture of
the 2,4-dibenzoylated 25 and the 2-monobenzoylated compound
evaporated and after flash chromatography 27 (44 mg, 0.05 mmol,
59%) was obtained. Conversion following GP1: 27 (44 mg,
0.05 mmol), 15 (76 mg, 0.15 mmol), anhydrous CH2Cl2 (10 mL),
˚
4-A mol. sieves, argon, room temperature, 1 h, DMTST (77 mg,
0.30 mmol), 16 h. After flash chromatography with toluene/EA,
20:1, a mixture of trisaccharide and disaccharide (28, 20 mg, 1:3.5
by 1H NMR) was obtained. TLC (toluene/EA, 20:1): Rf ϭ 0.29
(436 mg) was obtained (ഠ 1.6:1 by 1H NMR). In a second chroma- (UV, H2SO4). MALDI-TOF-MS (DHB, positive mode): 1866.24
tographic approach 25 (56 mg, 0.08 mmol, 11%) was obtained
along with 370 mg of the mixture. Syrup, C34H52O7SSi2 (mol. mass
661.010 g/mol). TLC (PE/EA, 9:1): Rf ϭ 0.48 (UV, H2SO4). 1H [M
[M ϩ Na]ϩ (calcd.: 1865.88), 1882.13 [M ϩ K]ϩ (calcd.: 1881.85)
(trisaccharide). 1408.07 [M ϩ Na]ϩ (calcd.: 1407.74), 1424.00
ϩ
K]ϩ (calcd.: 1423.71) (disaccharide). 1H NMR (400
NMR (400 MHz, CDCl3): δ ϭ 8.20Ϫ8.12, 7.74- 7.41 (m, 10 H, 2 MHz, CDCl3):
δ
ϭ
8.12Ϫ8.05, 8.02Ϫ7.94, 7.84Ϫ7.80,
ϫ C6H5COO), 5.34Ϫ5.23 (m, 2 H, H-2, H-4), 4.58 (d, 1 H, H-1, 7.63Ϫ7.35, 7.27Ϫ7.14 (m, C6H5COO), 6.90Ϫ6.85 (m, 2 ϫ 2 H,
3
3J1,2 ϭ 9.9 Hz), 4.17 (dd ഠ t, 1 H, H-3, J2,3
3.76Ϫ3.58 (m, 3 H, H-5, H-6a, H-6b), 2.82Ϫ2.58 (m, 2 H, H-4Јtrisaccharide), 5.79 (dd, 1 H, H-3ЈЈdisaccharide
SCH2CH3), 1.46 (t, 3 H, SCH2CH3), 1.06, 0.86 [2 ϫ s, 2 ϫ 9 H, 2 3J3ЈЈ,4ЈЈ ϭ 10.4 Hz), 5.70 (m), 5.61 (dd, 1 H, H-2ЈЈdisaccharide
ϭ
3J3,4 ϭ 8.8 Hz), CH3OC6H4CH2O), 6.09 (d, 1 H), 5.88Ϫ5.64 (m, H-3ЈЈtrisaccharide
,
,
3J2ЈЈ,3ЈЈ ϭ 3.5,
,
ϫ (CH3)3CSiMe2], 0.12, 0.10, Ϫ0.02, Ϫ0.04 [4 ϫ s, 4 ϫ 3 H, 2 ϫ 3J1ЈЈ,2ЈЈ ϭ 1.6, J2ЈЈ,3ЈЈ ϭ 3.5 Hz), 5.55 (dd, 1 H, Hdisaccharide
,
3J ϭ
3
tBuSi(CH3)2] ppm.
4.4, 3J ϭ 5.4 Hz), 5.37 (br. d, 1 H, H-6disaccharide 3J ϭ 5.1 Hz),
,
5.20 (br. s, 1 H, H-1ЈЈdisaccharide), 5.02 4.92 (2 ϫ d, 2 ϫ 1 H,
H-1ЈЈtrisaccharide, H-1ЈЈЈtrisaccharide), 4.59Ϫ4.49 (m), 4.44, 4.40 (2 ϫ d,
(22R,25R)-3β-(2,4-Di-O-benzoyl-3,6-di-O-tert-butyldimethylsilyl-β-
3
D-glucopyranosyloxy)-26-O-p-methoxybenzyloxy-5-furosten
(26):
2 ϫ 1 H, CH3OC6H4CH2Odisaccharide, J ϭ 11.7 Hz), 4.38 (d, 1 H,
H-1Ј, 3J1Ј,2Ј ϭ 7.6 Hz), 4.31 (m, 1 H, H-16), 4.23Ϫ4.10, 3.95Ϫ3.79,
3.70Ϫ3.50 (3 ϫ m), 3.80 (s, 3 H, CH3OC6H4CH2O), 3.39 (m, 1 H,
H-5Јdisaccharide), 3.37Ϫ3.28 (m, 3 H, H-3, H-22, H-26a), 3.23 (dd, 1
Conversion following GP: Donor 25 (56 mg, 0.08 mmol), acceptor
10 (45 mg, 0.08 mmol), argon, anhydrous diethyl ether (20 mL),
room temperature, 1 h, DMTST (66 mg, 0.25 mmol), TLC PE/
Et2O, 1:1 [Rf (25) ϭ 0.83, Rf (10) ϭ 0.19], room temperature, 16 h,
0.05 mL triethylamine, 15 min. A suitable amount of silica gel was
added to the reaction mixture, the solvent was evaporated and the
powdery mixture was poured onto a pre-packed column of silica
gel (PE) and chromatographed with PE/Et2O, 1:0 Ǟ 10:1 Ǟ 5:1 Ǟ
2:1. Compound 26 (94 mg, 0.08 mmol, quant.) was obtained.
Syrup, C67H98O11Si2 (mol. mass 1135.659 g/mol), [α]2D0 ϭ Ϫ5.0 (c ϭ
1, CHCl3). TLC (PE/Et2O, 1:1): Rf ϭ 0.64 (UV, H2SO4). 1H NMR
(400 MHz, CDCl3): δ ϭ 8.60Ϫ7.95, 7.58Ϫ7.38 (2 ϫ m, 10 H, 2 ϫ
3
2
H, H-26b, J25,26 ϭ 6.6, J26a,26b ϭ 8.8 Hz), 2.88 (d, 1 H, OH),
2.18Ϫ0.82 (m, steroid H, 2 ϫ (CH3)3CMe2Si), 0.20Ϫ0.02 [2 ϫ
(CH3)3CMe2Si] ppm.
(22R,25R)-3β-(2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranosyloxy)-26-
tert-butyldimethylsilyloxy-5-furosten (30): Conversion following
GP: 14 (400 mg, 0.75 mmol), 18 (579 mg, 0.90 mmol), argon, fresh
˚
anhydrous diethyl ether (130 mL), 1 spatula of freshly activated 4-A
mol. sieves, 1 h, room temperature, DMTST (697 mg, 2.70 mmol),
4.5 h. TLC PE/EA, 2:1 [Rf (14) ϭ 0.42, Rf (18) ϭ 0.47] and toluene/
acetone, 20:1 [Rf (14) ϭ 0.18, Rf (18) ϭ 0.18]. Triethylamine
(2.0 mL), 15 min. A suitable amount of silica gel was added to the
reaction mixture, the solvent was evaporated and the powdery mix-
ture was poured on a pre-packed column of silica gel (PE) and
chromatographed with PE/EA, 4:1. Compound 30 (183 mg,
0.16 mmol, 22%) was obtained. Colourless crystals, C67H84O12Si
(1109.462): calcd. C 72.53, H 7.63; found C 71.59, H 7.65 (The
deviation in the elementary analysis is caused by partial hydrolysis
of the TBDMS group during storage.). M.p. 117 °C, [α]2D0 ϭ Ϫ2.7
(c ϭ 0.15, CHCl3). TLC (PE/EA, 2:1): Rf ϭ 0.60, (toluene/acetone
20:1): Rf ϭ 0.74 (UV, H2SO4). MALDI-TOF-MS (DHB, positive
mode): 1131.82 [M ϩ Na]ϩ (calcd.: 1131.56), 1147.72 [M ϩ K]ϩ
(calcd.: 1147.54). 1H NMR (500 MHz, C6D6): δ ϭ 8.21, 8.17, 8.08,
C6H5COO), 7.25, 6.84 (2 ϫ m, 2 ϫ 2 H, CH3OC6H4CH2O),
3
5.20Ϫ5.13 (m, 3 H, H-6, H-2Ј, H-4Ј), 4.64 (d, 1 H, H-1Ј, J1Ј,2Ј
ϭ
8.0 Hz), 4.41, 4.37 (2 ϫ d, 2 ϫ 1 H, CH3OC6H4CH2O, 3J ϭ
11.7 Hz), 4.23 (ddd ഠ dt, 1 H, H-16, J ϭ 5.1, 7.7 Hz), 4.12 (dd ഠ
t, 1 H, H-3Ј, J2Ј,3Ј ϭ J3Ј,4Ј ϭ 9.2 Hz), 3.76 (s, 3 H, CH3OC6H4-
CH2O), 3.73Ϫ3.58 (m, 3 H, H-5Ј, H-6aЈ, H-6bЈ), 3.45 (m, 1 H, H-
3), 3.30Ϫ3.23 (m, 2 H, H-22, H-26a), 3.19 (dd, 1 H, H-26b,
3
3
3
3J25,26b
ϭ 6.8, 9.0 Hz), 2.18Ϫ0.82 [m, steroid H, 2 ϫ
(CH3)3CMe2Si], Ϫ0.02, Ϫ0.06, Ϫ0.24, Ϫ0.26 [2 ϫ (CH3)3CMe2Si]
ppm. 13C NMR (100.67 MHz, CDCl3): δ ϭ 165.15, 165.06 (2 ϫ
C6H5COO), 158.96, 130.92 (CH3OCC4H4CCH2O), 140.56 (C-5),
135.18, 133.20Ϫ128.38 (2
ϫ
C6H5COO), 129.15, 113.77
(CH3OCC4H4CCH2O), 121.48 (C-6), 99.88 (C-1Ј), 90.48 (C-22),
83.26 (C-16), 79.53, 75.47, 74.97, 73.76, 72.91 (C-3, C-2Ј, C-3Ј, C-
4Ј, C-5Ј), 75.78 (C-26), 72.81 (CH3OC6H4CH2O), 65.74 (C-6Ј),
55.44 (CH3OC6H4CH2O), 65.35, 63.64, 57.11, 50.32, 41.02Ϫ14.02
[steroid C, (CH3)3CMe2Si)], Ϫ4.05, Ϫ4.22, Ϫ4.97, Ϫ5.08
[(CH3)3CMe2Si)] ppm.
3
7.99 (4 ϫ m ഠ d, 4 ϫ 2 H, 4 ϫ o-C6H5COO, 4 ϫ J ϭ 7.25 Hz),
7.13Ϫ6.76 (m, 12 H, 4 ϫ m/p-C6H5COO), 6.22 (dd ഠ t, 1 H, H-
3
3
3Ј, J2Ј,3Ј
ϭ
3J3Ј,4Ј ϭ 9.8 Hz), 5.97 (dd, 1 H, H-2Ј, J1Ј,2Ј ϭ 8.8,
3J2Ј,3Ј ϭ 9.2 Hz), 5.89 (t, 2 H, H-4Ј, 3J3Ј,4Ј ϭ J4Ј,5Ј ϭ 9.5 Hz), 5.25
(br. d, 1 H, H-6, J ϭ 5.0 Hz), 4.76 (d, 1 H, H-1Ј, J1Ј,2Ј ϭ 8.2 Hz),
3
3
3
2
(22R,25R)-[3,6-Di-O-tert-butyldimethylsilyl-(2,3,4-tetra-O-benzoyl- 4.63 (dd, 1 H, H-6Јa, J5Ј,6Јa ϭ 2.8, J6Јa,6Јb ϭ 12.0 Hz), 4.53 (dd,
α-
L
-rhamnopyranosyl)-(1Ǟ2)-(2,3,4-tetra-O-benzoyl-α-
L
-rhamno- 1 H, H-6Јb, 3J5Ј,6Јb ϭ 5.2, 2J6Јa,6Јb ϭ 12.0 Hz), 4.29 (m, 1 H, H-16),
3
3
pyranosyl)-(1Ǟ4)-β-
D
-glucopyranosyloxy]-(1-OǞ3β)-26-O-
3.75 (ddd, 1 H, H-5Ј, J4Ј,5Ј ϭ 9.5, J5Ј,6Јa ϭ 2.8, 3J5Ј,6Јb ϭ 5.2 Hz),
p-methoxybenzyloxy-5-furosten and (22R,25R)-[3,6-Di-O-tert-butyl-
dimethylsilyl-(2,3,4-tetra-O-benzoyl-α-
β- -glucopyranosyloxy]-(1-OǞ3β)-26-O-p-methoxybenzyloxy-5-
3.65 (m, 1 H, H-3), 3.51Ϫ3.30 (m, 3 H, H-26a, H-26b, H-22), 2.42
-rhamnopyranosyl)-(1Ǟ2)- (m, 1 H, H-4a), 2.31 (m, 1 H, H-4b), 2.05Ϫ1.92 (m, 2 H),
1.85Ϫ0.82 (m, steroid H), 1.02Ϫ0.82 (m, tBuMe2Si, CH3-18, -19, -
L
D
Eur. J. Org. Chem. 2003, 4003Ϫ4011
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4009

R. Suhr, M. Lahmann, S. Oscarson, J. Thiem
21, -27), 0.09, 0.07 (2 ϫ s, 2 ϫ 3 H, tBuMe2Si) ppm. 13C NMR (CH3-27), 39.61, 37.27, 32.41, 32.18, 31.19, 30.26, 29.84, 20.81
FULL PAPER
(100.67 MHz, C6D6): δ ϭ 165.99Ϫ165.47 (4 ϫ C6H5COO), 140.08
(C-5), 133.28Ϫ132.92, 130.15Ϫ130.00, 128.61Ϫ128.34 (4
(CH2-1, -2, -7, -11, -12, -15, -23, -24), 65.45, 57.12, 50.26, 31.70
(CH-8, -9, -14, -17), Ϫ5.19, Ϫ5.21 (tBuMe2Si) ppm.
ϫ
C6H5COO), 121.90 (C-6), 100.43 (C-1Ј), 90.52 (C-22), 83.41 (C-
16), 80.08 (C-3), 73.80 (C-3Ј), 72.81 (C-2Ј), 72.44 (C-5Ј), 70.62 (C-
4Ј), 68.01 (C-26), 63.38 (C-6Ј), 39.49 (C-4), 41.10, 36.50 (C-10, C-
13), 26.20 [(CH3)3CSi], 19.25, 19.07, 17.05, 16.58 (CH3-18, Ϫ19,
Ϫ21, Ϫ27), 18.52 [(CH3)3CSi], 65.80, 57.22, 50.08, 38.35, 36.04,
31.85 (CH-8, 9, 14, 17, 20, 25), 39.61, 37.48, 32.72, 32.44, 31.51,
30.75, 30.05, 21.01 (CH2-1, -2, -7, -11, -12, -15, -23, -24), Ϫ5.17,
Ϫ5.19 (tBuMe2Si) ppm.
(22R,25R)-[3,6-Di-O-benzoyl-(2,3,4-tetra-O-benzoyl-α-
rhamnopyranosyl)-(1Ǟ2)-(2,3,4-tetra-O-benzoyl-α- -rhamno-
pyranosyl)-(1Ǟ4)-β- -glucopyranosyloxy]-(1-OǞ3β)-26-O-tert-
butyldimethylsilyloxy-5-furosten (33) and (22R,25R)-[3,6-Di-O-
benzoyl-(2,3,4-tetraO-benzoyl-α- -rhamnopyranosyl)-(1Ǟ2)-β-
L-
L
D
L
D-
glucopyranosyloxy]-(1-OǞ3β)-26-O-tert-butyldimethylsilyloxy-5-
furosten (34): Conversion following GP: 32 (30 mg, 0.03 mmol), 15
(52 mg, 0.09 mmol), argon, fresh anhydrous diethyl ether (20 mL),
˚
1 spatula of freshly activated 4-A mol. sieves, 1 h, room tempera-
(22R,25R)-3β-(β-D-Glucopyranosyloxy)-26-tert-butyldimethyl-
silyloxy-5-furosten (31): Compound 30 (150 mg, 0.14 mmol) was
dissolved in a mixture of anhydrous CH2Cl2 (10 mL) and anhy-
drous MeOH (10 mL), and the pH was raised to 8.5 by addition
of solid sodium methoxide. The mixture was stirred for 4 h at room
temperature until TLC PE/EA, 1:3 [Rf (30) ϭ 0.91] and EA/EtOH,
10:1 [Rf (30) ϭ 0.97] showed complete conversion. The pH was
lowered to 6 by addition of AcOH/EtOH, 20:1. Flash chromatogra-
phy with CH2Cl2/MeOH/NEt3, 5:1:0.1 yielded 31 (65 mg,
0.09 mmol, 65%) and slightly impure product (40 mg). Colourless
solid, C39H68O8Si (mol. mass 693.038 g/mol), decomposition: Ͼ
270 °C. TLC (PE/EA, 1:3): Rf ϭ 0, (EA/EtOH, 10:1): Rf ϭ 0.29
(UV, H2SO4). MALDI-TOF-MS (DHB, positive mode): 715.55 [M
ϩ Na]ϩ (calcd.: 715.46), 731.43 [M ϩ K]ϩ (calcd.: 731.43).
ture, DMTST (52 mg, 0.20 mmol), 4.5 days. Observation of the re-
action was carried out using TLC [PE/EA, 3:1, Rf (32) ϭ 0.16, Rf
(15) ϭ 0.41 and toluene/acetone, 10:1, Rf (32) ϭ 0.29, Rf (15) ϭ
0.77] and with MALDI-TOF-MS (subjection of the reaction mix-
ture on a DHB matrix). Triethylamine (0.1 mL), 10 min. A suitable
amount of silica gel was added to the reaction mixture, the solvent
was evaporated and the powdery mixture was poured onto a pre-
packed column of silica gel (toluene) and purified by flash chroma-
tography with toluene/acetone, 16:1, whereby 34 (6 mg, 4.4 µmol,
15%). MALDI-TOF-MS (DHB, positive mode): 1382.92
[M ϩ Na]ϩ (calcd.: 1381.65), 1398.66 [M ϩ K]ϩ (calcd.: 1397.62)]
and the 26,2Ј-di-α--rhamnopyranoside (5 mg, 2.9 µmol, 10%) were
obtained. Flash chromatography of the first fraction with toluene/
acetone, 16:1 yielded 33 (10 mg, 6 µmol, 18%).
(22R,25R)-3β-(3,6-Di-O-benzoyl-β-D-glucopyranosyloxy)-26-O-tert-
33: Colourless crystals, C107H120O24Si (mol. mass 1818.17 g/mol),
m.p. 109.4Ϫ110.1 °C. TLC (toluene/acetone, 10:1): Rf ϭ 0.83 (UV,
H2SO4). MALDI-TOF-MS (DHB, positive mode): 1839.85
[M ϩ Na]ϩ (calcd.: 1839.78), 1855.78 [M ϩ K]ϩ (calcd.: 1855.76).
1H NMR (500 MHz, C6D6): δ ϭ 8.25Ϫ7.91 (m, 16 H, 8 ϫ o-
C6H5COO), 7.14Ϫ6.69 (m, 24 H, 8 ϫ m/p-C6H5COO), 6.41 (dd, 1
butyldimethylsilyloxy-5-furosten (32): Compound 31 (65 mg,
0.09 mmol) and 1-(benzyloxy)benzotriazole[21,23] (61 mg, 0.2 mmol)
were dissolved in anhydrous dichloromethane (2 mL), and triethyl-
amine p. a. (30 µL) was added. The reaction mixture was stirred
for 2.5 days at room temperature until TLC showed complete con-
version of the starting material [PE/EA, 2:1 Rf (31) ϭ 0, Rf (1-
BBTZ) ϭ 0.44, Rf (by-products) ϭ 0.09, 0.22, 0.52, and toluene/
acetone, 10:1 Rf (31) ϭ 0, Rf (1-BBTZ) ϭ 0.59, Rf (by-products) ϭ
0.06, 0.17, 0.42]. After evaporation of the solvent and flash chroma-
tography with toluene/acetone, 12:1 Ǟ 6:1, compound 32 (30 mg,
0.03 mol, 33%) was obtained. The small amount of by-products
was not characterized. Amorphous substance, C53H76O10Si (mol.
mass 901.250 g/mol), [α]D20 ϭ ϩ25.3 (c ϭ 1.2, CHCl3). TLC (PE/
EA, 2:1): Rf ϭ 0.34, (toluene/acetone, 10:1): Rf ϭ 0.25 (UV,
H2SO4). MALDI-TOF-MS (DHB, positive mode): 924.26
3
3
H, H-3ЈЈ, J2ЈЈ,3ЈЈ ϭ 3.2, J3ЈЈ,4ЈЈ ϭ 10.4 Hz), 6.35 (dd, 1 H, H-3ЈЈЈ,
3
3J2ЈЈЈ,3ЈЈЈ ϭ 3.2, J3ЈЈЈ,4ЈЈЈ ϭ 10.4 Hz), 6.22Ϫ6.12 (m, 3 H, H-4ЈЈ, H-
3
2ЈЈЈ, H-4ЈЈЈ), 6.06 (dd, 1 H, H-3Ј, J ϭ 9.5 Hz), 6.04 (dd, 1 H, H-
3
3
2ЈЈ, J1ЈЈ,2ЈЈ ϭ 1.6, J2ЈЈ,3ЈЈ ϭ 3.2 Hz), 5.62 (br. d, 1 H, H-6, J ϭ
5.0 Hz), 5.53 (d, 1 H, H-1ЈЈ, 3J1ЈЈ,2ЈЈ ϭ 1.3 Hz), 5.50 (d, 1 H, H-1ЈЈЈ,
3J1ЈЈЈ,2ЈЈЈ ϭ 1.3 Hz), 5.18 (dq, 1 H, H-5ЈЈ, J4ЈЈ,5ЈЈ ϭ 10.1, J5ЈЈ,6ЈЈ
ϭ
3
3
6.3 Hz), 5.09 (dd, 1 H, H-6Јa, J5Ј,6Јa ϭ 1.9, 2J6Јa,6Јb ϭ 12.3 Hz),
3
4.83 (dd, 1 H, H-6Јb, 3J5Ј,6Јb ϭ 4.7, 2J6Јa,6Јb ϭ 12.3 Hz), 4.55 (dq, 1
3
3
H, H-5ЈЈЈ, J4ЈЈЈ,5ЈЈЈ ϭ 9.7, J5ЈЈ,6ЈЈ ϭ 6.3 Hz), 4.49 (d, 1 H, H-1Ј,
3J1Ј,2Ј ϭ 7.9 Hz), 4.35 (m, 1 H, H-16), 4.20Ϫ4.12 (m, 2 H, H-2Ј,
1
[M ϩ Na]ϩ (calcd.: 923.51), 940.28 [M ϩ K]ϩ (calcd.: 939.49). H
3
H-4Ј), 3.78 (m, 1 H, H-3), 3.49 (dd, 1 H, H-26a, J25,26a ϭ 5.4,
NMR (400 MHz, CDCl3): δ ϭ 8.07Ϫ8.00 (m, 4 H, 2 ϫ o-
C6H5COO), 7.57Ϫ7.51 (m, 2 H, 2 ϫ p-C6H5COO), 7.44Ϫ7.38 (m,
4 H, 2 ϫ m-C6H5COO), 5.30 (br. d, 1 H, H-6, J ϭ 5.0 Hz), 5.18
(dd ഠ t, 1 H, H-3Ј, 3J2Ј,3Ј ϭ 8.8, 3J3Ј,4Ј ϭ 9.2 Hz), 4.64Ϫ4.60 (m, 2
H, H-6Ј), 4.51 (d, 1 H, H-1Ј, 3J1Ј,2Ј ϭ 7.6 Hz), 4.27 (m, 1 H, H-16),
2J26a,26b ϭ 9.5 Hz), 3.46Ϫ3.40 (m, 2 H, H-26b, H-22), 3.38 (ddd, 1
3
3
3
H, H-5Ј, J4Ј,5Ј ϭ 9.5, J5Ј,6Јa ϭ 2.2, J5Ј,6Јb ϭ 4.7 Hz), 2.88 (m, 1
H, H-4a), 2.69 (m, 1 H, H-4b), 2.12Ϫ2.03 (m, 2 H), 1.95 (m, 1 H),
1.83Ϫ0.85 (m, steroid H), 1.58 (d, 3 H, H-6ЈЈ, J5ЈЈ,6ЈЈ ϭ 6.3 Hz),
3
3
1.02Ϫ1.00 (m, tBuMe2Si, CH3-21), 0.98 (d, 3 H, CH3-27, J25,27
ϭ
3
3.73Ϫ3.69 (m, 2 H, H-4Ј, H-5Ј), 3.64 (dd, 1 H, H-2Ј, J1Ј,2Ј ϭ 8.5,
6.9 Hz), 0.84Ϫ0.82 (m, CH3-18, -19), 0.09 (s, 6 H, tBuMe2Si) ppm.
3J2Ј,3Ј ϭ 8.8 Hz), 3.54 (m, 1 H, H-3), 3.43 (dd, 1 H, H-26a,
13C NMR (125.76 MHz, C6D6):
C6H5COO), 142.49 (C-5), 134.91, 133.29Ϫ132.74 (8
C6H5COO), 130.47, 130.16Ϫ130.00 (8
δ
ϭ
166.06Ϫ165.27 (8
ϫ
2
3
3J25,26a ϭ 5.7, J26a,26b ϭ 9.8 Hz), 3.35 (dd, 1 H, H-26b, J25,26b
ϭ
ϫ
p-
2
6.6, J26a,26b ϭ 9.8 Hz), 3.22 (br. s, 1 H, 4Ј-OH), 3.28 (dt, 1 H, H-
22, 3J ϭ 4.1, 7.8 Hz), 2.50 (br. s, 1 H, 2Ј-OH), 2.34 (m, 1 H, H-
4a), 2.25 (m, 2 H, H-4b), 2.00Ϫ1.88 (m, 3 H), 1.75Ϫ0.82 (m, steroid
H), 0.97, 0.85 (d, CH3-21, -27), 0.95, 0.77 (s, CH3-18, -19), 0.86 (s,
9 H, tBuMe2Si), Ϫ0.03 (2 ϫ s, 2 ϫ 3 H, tBuMe2Si) ppm. 13C NMR
(100.67 MHz, CDCl3): δ ϭ 167.95, 166.89 (2 ϫ C6H5COO), 140.36
(C-5) 133.64, 133.29, 130.17, 130.08, 129.99, 129.55, 128.58, 128.52,
128.36 (2 ϫ C6H5COO), 122.09 (C-6), 101.62 (C-1Ј), 90.56 (C-22),
83.25 (C-16), 79.97, 78.74, 74.46, 72.29, 70.00 (C-3, C-2Ј, C-3Ј, C-
4Ј, C-5Ј), 68.30 (C-26), 64.03 (C-6Ј), 38.99 (C-4), 38.02 (C-20),
ϫ
o-C6H5COO),
128.68Ϫ128.35 (m-C6H5COO), 122.30 (C-6), 100.37 (C-1Ј), 99.48
(C-1ЈЈЈ), 98.54 (C-1ЈЈ), 90.56 (C-22), 83.48 (C-16), 79.78 (C-3),
78.11 (C-4Ј), 78.02 (C-2Ј), 77.73 (C-3Ј), 73.54 (C-5Ј), 72.73 (C-4ЈЈ),
72.01, 71.96 (C-2ЈЈЈ, C-4ЈЈЈ), 71.42 (C-2ЈЈ), 70.34 (C-3ЈЈ, C-3ЈЈЈ),
68.58, 68.50 (C-5ЈЈ, C-5ЈЈЈ, C-26), 65.92 (C-17), 63.04 (C-6Ј), 57.29
(C-14), 50.60 (C-9), 40.00Ϫ20.00 (steroid C), 26.57 [(CH3)3CSi],
17.60, 17.07, 15.59, 14.21 (CH3-18, -19, -21, -27), Ϫ 9.95 (tBu-
Me2Si) ppm.
36.11 (C-25), 40.84, 36.92 (C-10, C-13), 26.13 [(CH3)3CSi], 19.47, 34: Syrup, C80H98O17Si (mol. mass 1359.71 g/mol). TLC (toluene/
16.55 (CH3-18, Ϫ19), 19.22 (CH3-21), 18.49 [(CH3)3CSi], 16.87 acetone 10:1): Rf ϭ 0.31 (UV, H2SO4). MALDI-TOF-MS (DHB,
4010
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4003Ϫ4011

Synthesis of Dihydrodiosgenin Glycosides
FULL PAPER
[7]
[8]
[9]
positive mode): 1382.92 [M ϩ Na]ϩ (calcd.: 1381.65), 1398.66
[M ϩ K]ϩ (calcd.: 1397.62). 1H NMR (500 MHz, C6D6): δ ϭ
8.20Ϫ7.80 (m, 10 H, 5 ϫ o-C6H5COO), 7.15Ϫ6.60 (m, 15 H, 5 ϫ
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5355Ϫ5356.
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3
3
m/p-C6H5COO), 6.43 (dd, 1 H, H-3ЈЈ, J2ЈЈ,3ЈЈ ഠ 0, J3ЈЈ,4ЈЈ
ϭ
3
3
10.7 Hz), 6.21 (dd, 1 H, H-4ЈЈ, J3ЈЈ,4ЈЈ ϭ 10.7, J4ЈЈ,5ЈЈ ϭ 9.2 Hz),
5.97 (dd ഠ br. s, 1 H, H-2ЈЈ), 6.63Ϫ5.53 (m, 3 H, H-1ЈЈ, H-3Ј, H-
6), 5.12 (m, 1 H, H-5ЈЈ), 4.68Ϫ4.48 (m, 2 H, H-6Јa, H-6Јb), 4.33
(d, 1 H, H-1Ј, 3J1Ј,2Ј ϭ 9.2 Hz), 4.27 (m, 1 H, H-16), 4.12 (dd, 1 H,
H-2Ј), 3.80Ϫ3.20 (m, 6 H, H-3, H-4Ј, H-26a, H-5Ј, H-26b, H-22),
2.80 (m, 1 H, H-4a), 2.68 (m, 1 H, H-4b), 2.15Ϫ0.70 (m, steroid
H, CH3-6ЈЈ, tBuMe2Si), 0.09, Ϫ 0.03 (2 ϫ s, 2 ϫ 3 H, tBuMe2Si)
ppm.13C NMR (125.76 MHz, C6D6): δ ϭ 167.0Ϫ163.0 (5 ϫ
C6H5COO), 141.1 (C-5), 134.0Ϫ128.0 (5 ϫ C6H5COO), 122.3 (C-
6), 100.4 (C-1Ј), 98.2 (C-1ЈЈ), 90.8 (C-22), 83.7 (C-16), 80.0 (C-3,
C-3Ј), 76.0 (C-2Ј), 74.8 (C-5Ј), 72.8 (C-4ЈЈ), 71.7 (C-2ЈЈ), 70.8 (C-
3ЈЈ), 70.6 (C-4Ј), 68.3 (C-26), 67.9 (C-5ЈЈ), 65.9 (C-17), 64.0 (C-6Ј),
57.4 (C-14), 51.0 (C-9), 42.0Ϫ15.5 [steroid C, (CH3)3CSi] ppm.
[10]
[11]
[12]
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Acknowledgments
Financial support from the EU (Program Carenet-2, Contract
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Received May 14, 2003
Eur. J. Org. Chem. 2003, 4003Ϫ4011
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4011