Synthesis of L-arabinopyranose containing hederagenin saponins

Article abstract of DOI:10.1016/j.tet.2005.03.003

The synthesis of eight hederagenin saponins, five of which are natural products, and their methyl esters is described as part of an ongoing study of the biological activity of triterpenoid saponins. Six disaccharides consisting of an l-arabinopyranose glycosylated in positions 2, 3, or 4 with a β-d-xylopyranose or a β-d-glucopyranose residue, respectively, were synthesized in good to excellent yields. The saponins were then prepared in good yields through glycosylation with a suitably protected hederagenin derivative followed by total deprotection and treatment with diazomethane.

Full text of DOI:10.1016/j.tet.2005.03.003

Tetrahedron 61 (2005) 4347–4362
Synthesis of L-arabinopyranose containing hederagenin saponins
*
´
Karen Ple, Martin Chwalek and Laurence Voutquenne-Nazabadioko
` ´
CNRS FRE 2715 Isolement, Structure, Transformations et Synthese de Substances Naturelles, Universite de Reims Champagne-Ardenne,
´
ˆ
IFR 53 Biomolecules, CPCBAI, Bat. 18, Moulin de la Housse, BP 1039, 51687 Reims, France
Received 7 January 2005; revised 24 February 2005; accepted 2 March 2005
Available online 24 March 2005
Abstract—The synthesis of eight hederagenin saponins, five of which are natural products, and their methyl esters is described as part of an
ongoing study of the biological activity of triterpenoid saponins. Six disaccharides consisting of an L-arabinopyranose glycosylated in
positions 2, 3, or 4 with a b-D-xylopyranose or a b-D-glucopyranose residue, respectively, were synthesized in good to excellent yields. The
saponins were then prepared in good yields through glycosylation with a suitably protected hederagenin derivative followed by total
deprotection and treatment with diazomethane.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the aglycone and the sugar moiety play an important role in
the evaluation of biological activity and must be considered
individually. It is thus essential to have access to all the
positional isomers of a given sugar moiety while keeping
the aglycone constant. We have implemented this strategy
as part of our ongoing study of the hemolytic activity of
hemi-synthetic hederagenin saponins in an attempt to better
understand the role of the sugar moiety on hemolysis.4
Having previously synthesized a-hederin and its positional
isomers with respect to the L-rhamnopyranosyl-L-arabino-
pyranose disaccharide moiety5 the synthesis of two
Saponins are triterpene or steroid glycosides which are
found in a wide variety of plants and certain marine
organisms.1 Interest in saponins is rapidly increasing due to
their numerous biological properties,2,3 but a limiting factor
in their evaluation is often the small amounts obtained from
natural product extraction. Chemical synthesis offers an
alternative to saponin extraction in plants, and opens
the door to the preparation of tailor-made molecules. In
the study of saponin structure–activity relationships, both
Figure 1. D-Xyl-L-Ara and D-Glc-L-Ara hederagenin saponins.
Keywords: Saponins; Glycosylation; Hederagenin; Natural product synthesis.
*
Corresponding author. Tel.: C33 3 26 91 84 19; fax: C33 3 26 91 35 96; e-mail: karen.ple@univ-reims.fr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.003

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4348
additional families of hederagenin saponins was undertaken
(Fig. 1). While keeping an L-arabinopyranose as the first
sugar, a D-xylopyranose and a D-glucopyranose were chosen
as the second one in the disaccharide moiety. In total, we
wished to synthesize eight hederagenin saponins including
2 and 6 having a b configuration between the aglycone
and the sugar chain, normally not found in natural sources.
Five of the eight saponins are naturally occurring in plants
(1, 3, 5, 7, 8),1,6 and several of the saponins have shown
molluscicidal6b,7 (3, 5), hemolytic8 (5), and cytotoxic9 (5,7)
activities.
and benzyl b-L-arabinopyranose oligosaccharides.17 The
disaccharide was synthesized in low yield using a suitably
protected benzyl b-L-arabinopyranose derivative and an
acetobromoglucose in the presence of an excess of mercury
cyanide. More recently, Field et al. reported the synthesis of
two D-glucopyranose-L-arabinopyranose disaccharides
which are fragments of the oat root saponin Avenacin
A-1.18 The desired disaccharides were synthesized in good
yields using a thioglycoside donor.
We wish to describe here the efficient synthesis of
b-D-xylopyranosyl-a-L-arabinopyranose and b-D-gluco-
pyranosyl-a-L-arabinopyranose disaccharides and their use
in the synthesis of eight hederagenin saponins and their
methyl esters as part of a directed study of the hemolytic
activity of hederagenin saponins. To our knowledge, this is
the first reported synthesis of b-D-Xyl-(1/2)-a-L-Ara and
b-D-Glc-(1/3)-a-L-Ara disaccharides as well as that of
eight hederagenin saponins, five of which are natural
products.
While the synthesis of steroidal saponins has been widely
reported in the literature,10 that of triterpenoid saponins has
attracted less attention. A large majority of triterpenoid
saponin syntheses involve oleanolic acid as the aglycone,11
and the use of others remains rare (e.g., hederagenin,5
glycyrrhetic acid,12 ursolic acid,13 or medicagenic acid14).
Few examples exist in the literature concerning the
synthesis of disaccharides with an L-arabinopyranose at
the reducing end. In the b-D-xylopyranosyl-a-L-arabino-
pyranose series, several syntheses have been reported for the
disaccharide portion of the saponin OSW-1 (b-D-Xyl-(1/
3)-a-L-Ara).15 Deng et al. originally reported the use of a
benzyl L-arabinopyranose precursor with free hydroxyl
groups in positions 3 and 4 and a trichloroacetimidate
derivative of b-D-xylopyranose giving a mixture of
disaccharides with glycosylation in position 3 being the
predominant reaction.15e The same authors also reported
that glycosylation of a phenyl 1-thio-L-arabinopyranose
precursor with free hydroxyl groups in positions 3 and 4
resulted in the b-D-Xyl-(1/4)-a-L-Ara disaccharide as the
major reaction product.16 In the synthesis of Yu et al.15c the
target disaccharide b-D-Xyl-(1/3)-a-L-Ara was prepared
in 93% yield from a protected L-arabinopyranose derivative
and a D-xylopyranosyl trichloroacetimidate.
2. Results and discussion
The previously described L-arabinopyranose derivatives 9,
10 and 11 were the starting point for the disaccharide
syntheses.5 In the D-xylopyranose series, glycosylation with
2,3,4-tri-O-benzoyl-a-D-xylopyranosyl trichloroacetimi-
date19 (12) gave the desired disaccharides in good to
excellent yields (Scheme 1).
When the same glycosylation strategy was tried in the
D-glucopyranose series using 2,3,4,6-tetra-O-benzoyl-a-D-
glucopyranosyl trichloroacetimidate (16),20 the reaction
resulted in the isolation of the corresponding orthoesters
in good yields (75–92%) with no trace of the desired
disaccharides (Scheme 2). Modifying the reaction con-
ditions or attempting orthoester opening with excess
TMSOTf or HgBr2 resulted in total degradation of the
starting material. The use of the corresponding per-O-
benzoylated thioglycoside donor 1721 was also tried with
In the b-D-glucopyranose-a-L-arabinopyranose series, Lip-
tak et al. described the first synthesis of a b-D-glucopyr-
anosyl-(1/2)-a-L-arabinopyranose disaccharide derivative
in 1982 as part of a 13C NMR spectroscopy study of methyl
Scheme 1.

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4349
Scheme 2.
the arabinopyranose acceptor 10. Once again, the orthoester
was isolated in good yield.
Ethyl 2-O-benzoyl-3,4,6-tetra-O-benzyl-1-thio-b-D-gluco-
pyranoside (22) was then synthesized using an analogous
procedure described for D-galactose (Scheme 3).22 By
replacing the benzoate protecting groups in positions 3, 4
and 6 with benzyl groups we hoped to enhance the reactivity
of the thioglycoside donor, and avoid, if possible, further
orthoester formation.
Compound 22 was then successfully used as a donor in the
glycosylation reactions with the arabinopyranose acceptors
9, 10, and 11. The disaccharides were obtained in good to
moderate yields with no detectable orthoesters in the
reaction mixtures (Scheme 4).
One possible explanation for the moderate yield of
disaccharide 24 could be the steric hindrance created by
Scheme 3.
Scheme 4.

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4350
the addition of a D-glucopyranose in position 3 of the
L-arabinopyranose derivative 10. Optimization of the
glycosylation reaction at different temperatures or by
the addition of a larger quantity of the thioglycoside donor
(up to 3 equiv) did not increase the yield.
reaction and gave exclusive formation of the a anomers as
a result of neighboring group participation. For the
trichloroacetimidates 27 and 30 possessing a sugar residue
in position 2, the b anomers were isolated as the major
reaction products.
The anomeric MPM protecting groups of the disaccharides
(13–15, 23–25) were then removed in the presence of
aqueous trifluoroacetic acid at room temperature. The
resulting hemiacetal was reacted with trichloroacetonitrile
in the presence of DBU, giving good to excellent yields of
the corresponding trichloroacetimidates (Table 1).
To prepare the corresponding a anomers of these two
saponins, the coupling reaction was carried out in
acetonitrile. Use of this solvent is known to promote
equatorial bond formation in glycoside synthesis when
neighboring group participation is absent.23 Glycosylation
with 2 equiv of the donor in acetonitrile at K35 8C gave a
mixture of anomers with the desired a anomer being the
major reaction product in both cases (Table 3).
Table 1. Trichloroacetimidate formation
Separation of the two anomers was possible by reverse
1
phase HPLC in 100% acetonitrile. Based on the H NMR
coupling constants of the major a anomers (J1,2, J4,5a
and J4,5b), it was observed that for compound 40 with
a D-xylopyranosyl-L-arabinopyranose side chain the arabi-
nopyranose ring adopts a 1C4 conformation to relieve steric
hindrance. In the case of the saponin with a D-gluco-
pyranose-L-arabinopyranose side chain (41) the situation is
not as clear-cut as several coupling constants remain
undetermined.
Disaccharide
R1
R2
R3
Trichloro
acetimidate
Yield
13
14
15
23
24
25
Xyla
Bz
OBz
Xyl
Bz
Bz
Glc
Bz
Bz
Bz
Xyl
Bz
Bz
Glc
27
28
29
30
31
32
89%
80%
83%
78%
74%
77%
Bz
Glcb
Bz
Total deprotection of the saponin derivatives was performed
in one or two steps based on the starting compound. While
having previously reported the efficient removal of a
hederagenin allyl ester in the presence of pyrrolidine and
catalytic amounts of tetrakis(triphenylphosphine) palla-
dium(0) [Pd(PPh3)4],4,5 we sought to reduce the somewhat
long reaction times necessary to achieve complete depro-
tection. In a normal de-allylation reaction, excess pyrro-
lidine serves as a nucleophile, driving the reaction to
completion.24 A recent literature example describes the
deprotection of allylphenols in a 10% KOH/MeOH solution
in the presence of a catalytic amount of Pd/C.25 We felt that
replacing the pyrrolidine with an excess of KOH could lead
Bz
a XylZ(2,3,4-tri-O-benzoyl-b-D-xylopyranosyl).
b GlcZ(2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-glucopyranosyl).
Saponin synthesis was then performed with the activated
disaccharides 27–32 and the previously described allyl
hederagenate derivative 33.5 Coupling at low temperature in
the presence of a catalytic amount of TMSOTf gave the
protected saponins in excellent yields (Table 2).
As expected, the presence of a benzoate in position 2 of the
L-arabinopyranose moiety directed the glycosylation
Table 2. Hederagenin glycosylation
Trichloroacetimidate
R1
R2
R3
Protected saponin
Yield
28
29
31
32
27
30
Bz
Bz
Bz
Bz
Xyl
Glc
Xyla
Bz
Bz
Xyl
Bz
Glc
Bz
Bz
34
35
36
37
38
39
95%
94%
93%
95%
94%
85%
Glcb
Bz
Bz
Bz
a XylZ(2,3,4-tri-O-benzoyl-b-D-xylopyranosyl).
b GlcZ(2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-glucopyranosyl).

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4351
Table 3. Glycosylation in acetonitrile
Trichloro
acetimidate
R1
R2
Protected
saponin (a)
Yield
H-1Ara:
H-4Ara:
J1,2 (Hz)
J4,5a (Hz)
J4,5b (Hz)
27
30
Bz
Bn
H
CH2OBn
40
41
58% (a) C6% (b)
61% (a) C14% (b)
3.5
nd
3.2
Nd
7.1
6.4
to the deprotection of both the allyl and benzoyl protecting
groups in one step. It was found that heating the saponin in
the presence of 1 equiv of Pd(PPh3)4 in a 3% KOH solution
in methanol at 60 8C for 6 h afforded the completely
deprotected D-xylopyranosyl-L-arabinopyranose saponins
(1–4) or the partially protected D-glucopyranosyl-L-arabino-
pyranose ones in good yield. For the latter compounds, the
benzyl groups were then removed by hydrogenolysis in
the presence of Pd/C at atmospheric pressure (Table 4).
Hydrogenolysis or migration of the double bond in the
triterpenoid skeleton was not observed using these reaction
conditions. Successful deprotection was also possible with a
catalytic amount of Pd(PPh3)4 (0.3 equiv) in a mixture of
THF/3% KOH/MeOH at 60 8C, with the desired saponins
being isolated in fair to excellent yields. The use of as little
as 0.1 equiv of Pd(PPh3)4 was tried for the D-xylopyranosyl-
L-arabinopyranose saponins, but in most cases the yields
were poorer than those obtained with 0.3 equiv of catalyst.
The corresponding methyl esters (1a–8a) were then
Table 4. Total deprotection of saponins: optimization of reaction conditions
Protected
saponin
Deprotection
method
Saponin
R1
R2
R3
Yield
(1 equiv Pd)a
Yield
(0.3 equiv Pd)b
Yield
(0.1 equiv Pd)b
40
38
34
35
41
39
36
37
A
A
A
A
B
B
B
B
1
2
3
4
5
6
7
8
Xylc
Xyl
H
H
H
Xyl
H
H
H
Glc
H
H
H
H
Xyl
H
H
H
Glc
76%
64%
82%
84%
82%
88%
78%
82%
89%
84%
72%
74%
87%
82%
84%
65%
64%
88%
71%
66%
—
—
—
—
H
Glcd
Glc
H
H
Method A: 3% KOH/MeOH or THF/3% KOH/MeOH, Pd(PPh3)4, 60 8C. Method B: (1) 3% KOH/MeOH or THF/3% KOH/MeOH, Pd(PPh3)4, 60 8C; (2) Pd/C,
H2.
a 3% KOH/MeOH, 60 8C.
b THF/3% KOH/MeOH, 60 8C.
c XylZ(b-D-xylopyranosyl).
d GlcZ(b-D-glucopyranosyl).

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4352
prepared in quantitative yield by diazomethane treatment of
the acids 1–8.26
4.1.1. 4-Methoxybenzyl 2,3,4-tri-O-benzoyl-b-D-xylopyr-
anosyl-(1/2)-3,4-di-O-benzoyl-a-L-arabinopyranoside
(13). General method. In a typical experiment, 4-methoxy-
benzyl 3,4-di-O-benzoyl-a-L-arabinopyranoside 95 (1.5 g,
3.1 mmol), 2,3,4-tri-O-benzoyl-b-D-xylopyranosyl trichloro-
3. Conclusion
acetimidate19 12 (2.85 g, 4.7 mmol, 1.5 equiv) and 4 A
˚
powdered molecular sieves (6 g) were stirred for 1 h at room
temperature in CH2Cl2 (75 mL). The mixture was cooled
to K20 8C for 30 min followed by the dropwise addition
of a 0.1 M solution of TMSOTf in CH2Cl2 (1.55 mL,
0.16 mmol, 0.05 equiv). After stirring for 2 h at this
temperature, the reaction was quenched with triethylamine
(0.5 mL), filtered through Celite and evaporated. The crude
residue was purified by column chromatography (toluene/
acetone 99:1–98:2) to give 2.62 g (90%) of disaccharide 13
as an amorphous solid. RfZ0.47 (toluene/acetone 9:1). [a]D
C32.98 (c 1, CHCl3). 1H NMR (CDCl3): d 3.70 (dd, 1H, JZ
12.7, 5.3 Hz, H-50), 3.85 (s, 3H, OCH3), 3.91 (dd, 1H, JZ
12.3, 2.1 Hz, H-5), 4.29 (dd, 1H, JZ12.4, 4.7 Hz, H-5), 4.39
(dd, 1H, JZ7.3, 5.5 Hz, H-2), 4.57 (dd, 1H, JZ12.8,
3.7 Hz, H-50), 4.64 (d, 1H, JZ10.9 Hz, CH2MPM), 4.88 (d,
1H, JZ5.3 Hz, H-1), 4.98 (d, 1H, JZ10.9 Hz, CH2MPM),
5.25 (d, 1H, JZ4.2 Hz, H-10), 5.28 (m, 1H, H-40), 5.35
(dd, 1H, JZ6.2, 4.3 Hz, H-20), 5.53 (dd, 1H, JZ7.5, 3.4 Hz,
H-3), 5.56 (m, 1H, H-4), 5.71 (t, 1H, JZ6.3 Hz, H-30), 6.91
(d, 2H, JZ8.6 Hz, Ar-H), 7.21 (t, 1H, JZ7.7 Hz, Ar-H),
7.27 (t, 2H, JZ7.7 Hz, Ar-H), 7.36–7.49 (m, 11H, Ar-H),
7.59 (m, 2H, Ar-H), 7.73 (d, 2H, JZ7.5 Hz, Ar-H), 7.86 (d,
2H, JZ7.3 Hz, Ar-H), 7.99 (d, 2H, JZ7.2 Hz, Ar-H), 8.05
(d, 2H, JZ7.0 Hz, Ar-H), 8.06 (d, 2H, JZ7.0 Hz, Ar-H).
13C NMR (CDCl3): d 55.3 (OCH3), 60.8 (C-50), 61.5 (C-5),
68.0 (C-4), 68.7 (C-40), 69.2 (C-30), 69.8 (C-20), 70.7
(CH2MPM), 71.8 (C-3), 74.5 (C-2), 99.7 (C-10), 100.1
(C-1), 113.8 (CH), 128.1 (CH), 128.3 (CH), 128.4 (CH),
128.4 (CH), 128.4 (CH), 128.8 (C), 129.0 (C), 129.1 (C),
129.3 (C), 129.4 (C), 129.6 (CH), 129.7 (CH), 129.8 (CH),
129.9 (CH), 129.9 (CH), 133.0 (C), 133.2 (C), 133.3 (C),
133.4 (C), 159.4 (C), 164.8 (CO), 165.1 (CO), 165.4 (CO),
165.4 (CO), 165.5 (CO). Anal. Calcd for C53H46O15: C,
68.97; H, 5.02. Found: C, 68.60; H, 4.97.
Efficient chemical synthesis afforded a rapid access to eight
hederagenin saponins, five of which are naturally occurring
products whose synthesis has not yet been reported in the
literature. The synthesis of six disaccharides consisting of
an L-arabinopyranose substituted in positions 2, 3, or 4 with
a b-D-xylopyranose or a b-D-glucopyranose residue was
accomplished in good to excellent yields. Coupling of these
disaccharides to a protected hederagenin derivative and total
deprotection gave the desired saponins in 52–79% overall
yields. A deprotection method was developed with
Pd(PPh3)4 in the presence of KOH to efficiently remove
both the allyl ester and the sugar benzoyl protecting groups
in one step. The fully deprotected saponins were thus
obtained in good yields with significantly shorter reaction
times.
The preparation of triterpenoid saponins in larger quantities
facilitates the study of their biological activity. The strategy
presented here opens the door to the synthesis of a wide
variety of different saponins by simply changing the nature
of the aglycone. In addition, structure–activity relationships
can be more easily studied when all the positional isomers
of a given sugar moiety are readily accessible. The
hemolytic and cytotoxic activity of these molecules will
be reported in due course.
4. Experimental
4.1. General methods
All chemicals were reagent grade and used as supplied
unless otherwise noted. Dichloromethane (CH2Cl2) and
triethylamine were refluxed over calcium hydride and
distilled prior to use. All reactions were performed
under an Argon atmosphere unless otherwise indicated.
Analytical thin-layer chromatography (TLC) was per-
formed on E. Merck Silica Gel 60 F254 plates. Compounds
were visualized by dipping in an anisaldehyde solution in
ethanol and heating. Column chromatography was per-
formed using E. Merck Geduran Silica Gel Si 60 (40–
60 mM). Optical rotations were recorded at 22 8C with a
Perkin–Elmer 241 polarimeter. ESI-MS were recorded
with a Thermofinnigan quadripolar mass spectrometer
with positive ion data collected automatically. High
Resolution mass spectra were recorded on a Micromass
Q-TOF spectrometer. NMR spectra were obtained using a
4.1.2. 4-Methoxybenzyl 2,3,4-tri-O-benzoyl-b-D-xylopyr-
anosyl-(1/3)-2,4-di-O-benzoyl-a-L-arabinopyranoside
(14). This compound was prepared using the general method
described for 13. Reaction of 4-methoxybenzyl 2,4-di-O-
benzoyl-a-L-arabinopyranoside 105 (0.5 g, 1.0 mmol) and
trichloroacetimidate 12 (0.95 g, 1.6 mmol) gave 0.68 g
(70%) of 14. RfZ0.47 (toluene/acetone 9:1). [a]D C10.58
1
(c 1, CHCl3). H NMR (CDCl3): d 3.67 (dd, 1H, JZ12.4,
5.8 Hz, H-50), 3.75 (dd, 1H, JZ12.5, 2.2 Hz, H-5), 3.79 (s,
3H, OCH3), 4.32 (dd, 1H, JZ7.8, 3.3 Hz, H-3), 4.35 (m, 2H,
H-5, H-50), 4.52 (d, 1H, JZ12.2 Hz, CH2MPM), 4.63 (d,
1H, JZ5.7 Hz, H-1), 4.67 (d, 1H, JZ12.2 Hz, CH2MPM),
5.16 (d, 1H, JZ4.7 Hz, H-10), 5.22 (m, 1H, H-40), 5.34 (dd,
1H, JZ6.6, 5.0 Hz, H-20), 5.56 (m, 1H, H-4), 5.602 (dd, 1H,
JZ7.5, 6.0 Hz, H-2), 5.65 (t, 1H, JZ6.6 Hz, H-3 ), 6.71 (d,
2H, JZ8.5 Hz, Ar-H), 7.07 (d, 2H, JZ8.5 Hz, Ar-H), 7.20–
7.63 (m, 15H, Ar-H), 7.81 (d, 2H, JZ7.6 Hz, Ar-H), 7.95
(m, 4H, Ar-H), 8.01 (d, 2H, JZ7.5 Hz, Ar-H), 8.15 (d, 2H,
JZ7.4 Hz, Ar-H). 13C NMR (CDCl3): d 55.1 (OCH3), 60.9
(C-50), 61.7 (C-5), 68.8 (C-40), 69.3 (CH2MPM), 69.7 (C-4,
C-30), 70.0 (C-20), 70.8 (C-2), 76.5 (C-3), 98.4 (C-1), 100.4
(C-10), 113.6 (CH), 128.1 (CH), 128.3 (CH), 128.3 (CH),
1
Bruker Avance DRX 500 spectrometer (500 MHz for H
and 125 MHz for 13C). Elemental analyses were performed
on a Perkin–Elmer CHN 2400. The HPLC system
(Shimadzu) consisted of a solvent delivery system
equipped with dual pumps (LC-8A), and a UV spectro-
photometric detector (SPD-6A). Preparative HPLC was
performed using a Merck Hibar column (250 mm!25 mm;
Lichrospher RP 18 (7 mm)). Protected saponins were
detected at 230 nm.

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4353
128.4 (CH), 128.8 (C), 129.0 (C), 129.2 (C), 129.3 (C),
129.5 (CH), 129.7 (CH), 129.8 (CH), 129.8 (CH), 129.9
(CH), 132.9 (CH), 133.0 (CH), 133.2 (CH), 159.2 (C), 164.7
(CO), 164.9 (CO), 165.2 (CO), 165.4 (CO), 166.1 (CO).
Anal. Calcd for C53H46O15 ($0.7 CH3OH): C, 68.23; H,
5.20. Found: C, 68.23; H, 5.11.
cooled, EtOAc was added, and the solution was succes-
sively washed with H2O (3!), NaHCO3 (satd) (2!), and
H2O (2!). The organic layer was dried (Na2SO4),
evaporated, and the crude residue was purified by column
chromatography (cyclohexane/EtOAc 97:3) to give 6.8 g
(55%) of 20 as an oil. [a]D C17.18 (c 1, CHCl3). 1H NMR
(CDCl3): d 1.34 (t, 3H, JZ7.5 Hz, SCH2CH3), 1.99 (s, 3H,
CH3 orthoester), 2.69 (q, 2H, JZ7.5 Hz, SCH2CH3), 3.69
(dd, 1H, JZ10.9, 4.2 Hz, H-6a), 3.73 (dd, 1H, JZ10.9,
1.9 Hz, H-6b), 3.79 (dd, 1H, JZ9.5, 3.1 Hz, H-4), 3.89 (m,
1H, H-5), 3.99 (t, 1H, JZ3.0 Hz, H-3), 4.41 (d, 1H, JZ
11.5 Hz, CH2Ph), 4.58 (d, 1H, JZ12.2 Hz, CH2Ph), 4.60 (d,
1H, JZ11.5 Hz, CH2Ph), 4.63 (m, 1H, H-2), 4.64 (d, 1H,
JZ11.9 Hz, CH2Ph), 4.65 (d, 1H, JZ11.2 Hz, CH2Ph),
4.75 (d, 1H, JZ11.9 Hz, CH2Ph), 5.85 (d, 1H, JZ5.3 Hz,
H-1), 7.24–7.43 (m, 15H, Ar-H). 13C NMR (CDCl3): d 15.2
(SCH2CH3), 24.8 (SCH2CH3), 27.8 (CH3 orthoester), 69.1
(C-6), 70.1 (C-5), 71.7 (CH2Ph), 72.5 (CH2Ph), 73.4
(CH2Ph), 74.5 (C-2), 75.1 (C-4), 77.4 (C-3), 98.2 (C-1),
115.7 (C orthoester), 127.6 (CH), 127.8 (CH), 127.9 (CH),
128.0 (CH), 128.3 (CH), 128.4 (CH), 128.5 (CH), 137.6 (C),
137.8 (C), 138.1 (C). Anal. Calcd for C31H36O6S: C, 69.38;
H, 6.76. Found: C, 69.50; H, 6.88.
4.1.3. 4-Methoxybenzyl 2,3,4-tri-O-benzoyl-b-D-xylopyr-
anosyl-(1/4)-2,3-di-O-benzoyl-a-L-arabinopyranoside
(15). This compound was prepared using the general method
described for 13. Reaction of 4-methoxybenzyl 2,3-di-O-
benzoyl-a-L-arabinopyranoside 115 (0.5 g, 1.0 mmol) and
trichloroacetimidate 12 (0.95 g, 1.6 mmol) gave 0.89 g
(92%) of 15. RfZ0.46 (toluene/acetone 9:1). [a]D C9.08
(c 1, CHCl3). 1H NMR (CDCl3): d 3.85 (s, 3H, OCH3), 3.87
(m, 2H, H-5, H-50), 4.39 (dd, 1H, JZ12.0, 6.1 Hz, H-5),
4.48 (m, 1H, H-4), 4.57 (dd, 1H, JZ12.5, 3.6 Hz, H-50),
4.64 (d, 1H, JZ11.5 Hz, CH2MPM), 4.85 (d, 1H, JZ
4.8 Hz, H-1), 4.90 (d, 1H, JZ11.5 Hz, CH2MPM), 5.14 (d,
1H, JZ4.2 Hz, H-10), 5.31 (m, 1H, H-40), 5.42 (dd, 1H, JZ
6.0, 4.3 Hz, H-20), 5.53 (dd, 1H, JZ7.1, 3.2 Hz, H-3), 5.66
(dd, 1H, JZ7.0, 4.9 Hz, H-2), 5.75 (t, 1H, JZ6.0 Hz, H-30),
6.84 (d, 2H, JZ8.7 Hz, Ar-H), 7.14–7.62 (m, 17H, Ar-H),
7.82 (d, 2H, JZ8.3 Hz, Ar-H), 7.92 (d, 2H, JZ8.4 Hz, Ar-
H), 8.02–8.07 (m, 6H, Ar-H). 13C NMR (CDCl3): d 55.2
(OCH3), 60.5 (C-50), 62.3 (C-5), 68.4 (C-40), 68.8 (C-30),
69.5 (C-20), 69.8 (CH2MPM), 69.8 (C-2, C-3), 72.1 (C-4),
98.1 (C-1), 99.4 (C-10), 113.7 (CH), 128.2 (CH), 128.4
(CH), 128.5 (CH), 128.9 (C), 129.0 (C), 129.1 (C), 129.1
(C), 129.2 (C), 129.4 (C), 129.7 (CH), 129.8 (CH), 129.9
(CH), 129.9 (CH), 133.0 (CH), 133.0 (CH), 133.2 (CH),
133.3 (CH), 133.3 (CH), 159.2 (C), 164.8 (CO), 165.2 (CO),
165.5 (CO), 165.7 (CO). Anal. Calcd for C53H46O15: C,
68.97; H, 5.02. Found: C, 68.74; H, 4.71.
4.1.6. Ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-b-D-glu-
copyranoside (21). To a solution of orthoester 20 (6.6 g,
˚
12.3 mmol) in CH2Cl2 (26 mL) was added 4 A molecular
sieves (1.6 g), and the mixture was stirred for 1 h. The
solution was cooled to 0 8C, and TMSOTf (0.11 mL, mmol,
0.05 equiv) was slowly added. After stirring for 4 h, the
reaction was quenched by the addition of Et3N, filtered
through celite and evaporated to dryness to give 6.4 g of a
crude product which was used without further purification in
the next step. For identification purposes, a small amount of
product was purified by column chromatography (cyclo-
1
hexane/EtOAc 95:5). [a]D C8.68 (c 1, CHCl3). H NMR
4.1.4. 3,4,6-Tri-O-acetyl-1,2-O-(1-ethylthioethylidene)-
a-D-glucopyranose (19). A solution of HBr in AcOH
(33%, 38 mL) was slowly added to a stirring solution
of 1,2,3,4,6-penta-O-acetyl-D-glucopyranose (10.5 g,
26.9 mmol) in CH2Cl2 (38 mL) at 0 8C. After stirring
overnight at room temperature the reaction mixture was
diluted with CH2Cl2, washed with H2O (200 mL), NaHCO3
(satd) (2!200 mL), NaCl (satd) and dried with Na2SO4.
The solvent was evaporated and the residue (11 g) was taken
up in nitromethane (27 mL). After addition of 2,6-lutidine
(4.7 mL, 40.4 mmol, 1.5 equiv), ethanethiol (8.0 mL,
107.6 mmol, 4 equiv) and tetrabutylammonium bromide
(0.87 g, 2.7 mmol, 0.1 equiv), the reaction was stirred at
room temperature for 48 h. The solution was then
partitioned between EtOAc and aq NaHCO3. The aqueous
layer was extracted with EtOAc, dried (Na2SO4), filtered
and evaporated. The residue was purified by column
chromatography (cyclohexane/EtOAc 8:2–7:3) to give
9.2 g (83%) of 19 as an oil. 1H and 13C NMR spectra
were performed in deuterated chloroform and were in
accordance with published data.27
(CDCl3): d 1.33 (t, 3H, JZ7.4 Hz, SCH2CH3), 2.05 (s, 3H,
CH3CO), 2.78 (m, 2H, SCH2CH3), 3.57 (m, 1H, H-5), 3.74
(t, 1H, JZ9.0 Hz, H-3), 3.77 (t, 1H, JZ8.8 Hz, H-4), 3.78
(dd, 1H, JZ11.3, 4.5 Hz, H-6a), 3.83 (dd, 1H, JZ11.1,
1.9 Hz, H-6b), 4.43 (d, 1H, JZ10.0 Hz, H-1), 4.62 (d, 1H,
JZ12.2 Hz, CH2Ph), 4.64 (d, 1H, JZ11.0 Hz, CH2Ph),
4.68 (d, 1H, JZ12.1 Hz, CH2Ph), 4.76 (d, 1H, JZ11.4 Hz,
CH2Ph), 4.86 (d, 1H, JZ10.6 Hz, CH2Ph), 4.88 (d, 1H, JZ
11.3 Hz, CH2Ph), 5.10 (t, 1H, JZ9.2 Hz, H-2), 7.26–7.41
(m, 15H, Ar-H). 13C NMR (CDCl3): d 14.9 (SCH2CH3),
21.0 (CH3CO), 23.8 (SCH2CH3), 68.8 (C-6), 71.7 (C-2),
73.4 (CH2Ph), 75.1 (CH2Ph), 75.2 (CH2Ph), 77.8 (C-4), 79.4
(C-5), 83.4 (C-1), 84.4 (C-3), 127.6 (CH), 127.8 (CH), 127.9
(CH), 128.0 (CH), 128.3 (CH), 128.4 (CH), 137.9 (C), 138.1
(C), 138.2 (C), 169.6 (CO). Anal. Calcd for C31H36O6S: C,
69.38; H, 6.76. Found: C, 69.23; H, 6.88.
4.1.7. Ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-b-D-
glucopyranoside (22). The crude acetate 21 (6.3 g) was
dissolved in a solution of 3% KOH/MeOH (80 mL) and was
stirred overnight. The reaction mixture was then diluted
with EtOAc, washed with H2O (2!), dried (Na2SO4),
filtered and evaporated. The crude product was taken up in
pyridine (35 mL) and the reaction was cooled to 0 8C.
Benzoyl chloride (2.8 mL, 24.6 mmol, 2 equiv) was added
dropwise, and after warming to room temperature, the
reaction was heated to 70 8C for 6 h. The solvent was then
4.1.5. 3,4,6-Tri-O-benzyl-1,2-O-(1-ethylthioethylidene)-
a-D-glucopyranose (20). To a solution of orthoester 19
(8.9 g, 22.7 mmol) and benzyl bromide (8.7 mL,
72.6 mmol, 3.2 equiv) in dry THF (55 mL) was added
powdered KOH (14 g, 250 mmol, 11 equiv) and the reaction
was refluxed overnight with stirring. After the mixture was

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4354
removed under reduced pressure and the residue dissolved
in EtOAc. The organic layer was washed with H2O, 1 N
HCl, NaHCO3 (satd), and dried (Na2SO4). After filtration
and evaporation of the solvent under reduced pressure the
crude product was purified by column chromatography
(cyclohexane/EtOAc 92:8) to give 3.45 g (49%) of benzoate
Calcd for C61H58O14: C, 72.18; H, 5.76. Found: C, 71.91; H,
5.89.
4.1.9. 4-Methoxybenzyl 2-O-benzoyl-3,4,6-tri-O-benzyl-
b-D-glucopyranosyl-(1/3)-2,4-di-O-benzoyl-a-L-arabi-
nopyranoside (24). This compound was prepared using the
general method described for 23. Reaction of 4-methoxy-
benzyl 2,4-di-O-benzoyl-a-L-arabinopyranoside 105
(0.96 g, 2.0 mmol) and thioglycoside 22 (1.8 g, 3.0 mmol)
gave 1.06 g (52%) of 24. RfZ0.52 (toluene/acetone 9:1).
1
22 as an amorphous solid. [a]D C28.38 (c 1, CHCl3). H
NMR (CDCl3): d 1.31 (t, 3H, JZ7.4 Hz, SCH2CH3), 2.79
(m, 2H, SCH2CH3), 3.64 (m, 1H, H-5), 3.81 (dd, 1H, JZ
11.0, 4.7 Hz, H-6a), 3.83 (t, 1H, JZ8.8 Hz, H-4), 3.86 (dd,
1H, JZ10.8, 1.7 Hz, H-6b), 3.91 (t, 1H, JZ9.0 Hz, H-3),
4.60 (d, 1H, JZ10.0 Hz, H-1), 4.64 (d, 1H, JZ12.1 Hz,
CH2Ph), 4.67 (d, 1H, JZ11.5 Hz, CH2Ph), 4.69 (d, 1H, JZ
12.5 Hz, CH2Ph), 4.73 (d, 1H, JZ11.1 Hz, CH2Ph), 4.81 (d,
1H, JZ11.1 Hz, CH2Ph), 4.89 (d, 1H, JZ10.9 Hz, CH2Ph),
1
[a]D C45.48 (c 1, CHCl3). H NMR (CDCl3): d 3.57 (m,
1H, H-50), 3.64 (dd, 1H, JZ12.6, 2.2 Hz, H-5a), 3.66 (m,
2H, H-60a/b), 3.73 (t, 1H, JZ8.8 Hz, H-40), 3.76 (t, 1H, JZ
8.7 Hz, H-30), 3.79 (s, 3H, OCH3), 4.24 (dd, 1H, JZ7.9,
3.5 Hz, H-3), 4.31 (dd, 1H, JZ12.6, 4.7 Hz, H-5b), 4.39 (d,
1H, JZ12.0 Hz, CH2Ph), 4.42 (d, 1H, JZ11.9 Hz, CH2Ph),
4.45 (d, 1H, JZ12.4 Hz, CH2MPM), 4.50 (d, 1H, JZ
5.9 Hz, H-1), 4.55 (m, 2H, CH2Ph, CH2MPM), 4.58 (d, 1H,
JZ11.1 Hz, CH2Ph), 4.66 (d, 1H, JZ11.1 Hz, CH2Ph),
4.77 (d, 1H, JZ10.9 Hz, CH2Ph), 4.80 (d, 1H, JZ7.7 Hz,
H-10), 5.28 (t, 1H, JZ8.2 Hz, H-20), 5.50 (m, 2H, H-2, H-4),
6.69 (d, 2H, JZ8.7 Hz, Ar-H), 6.97 (d, 2H, JZ8.6 Hz,
Ar-H), 7.07–7.60 (m, 24H, Ar-H), 7.83 (d, 2H, JZ7.6 Hz,
Ar-H), 7.86 (d, 2H, JZ7.3 Hz, Ar-H), 8.16 (dd, 2H, JZ8.4,
1.2 Hz, Ar-H). 13C NMR (CDCl3): d 55.1 (OCH3), 61.9
(C-5), 68.9 (CH2MPM), 70.0 (C-4), 71.2 (C-2), 73.4
(CH2Ph), 73.4 (C-20), 74.8 (CH2Ph), 74.9 (CH2Ph), 75.2
(C-500, C-3), 77.7 (C-40), 82.7 (C-30), 98.1 (C-1), 101.1
(C-1 ), 113.6 (CH), 127.5 (CH), 127.6 (CH), 127.8 (CH),
127.8 (CH), 128.0 (CH), 128.1 (CH), 128.2 (CH), 128.3
(CH), 128.3 (CH), 128.4 (CH), 128.8 (C), 129.6 (CH), 129.7
(CH), 129.8 (C), 130.1 (CH), 132.6 (CH), 133.0 (CH), 137.7
(C), 137.9 (C), 138.2 (C), 159.1 (C), 164.7 (CO), 166.3
(CO). Anal. Calcd for C61H58O14: C, 72.18; H, 5.76. Found:
C, 71.95; H, 5.86.
5.38 (t, 1H, JZ9.6 Hz, H-2), 7.26–8.10 (m, 20H, Ar-H). 13
C
NMR (CDCl3): d 14.9 (SCH2CH3), 23.8 (SCH2CH3), 68.9
(C-6), 72.4 (C-2), 73.5 (CH2Ph), 75.1 (CH2Ph), 75.3
(CH2Ph), 77.9 (C-4), 79.5 (C-5), 83.4 (C-1), 84.3 (C-3),
127.6 (CH), 127.7 (CH), 127.8 (CH), 128.0 (CH), 128.2
(CH), 128.4 (CH), 129.8 (CH), 129.9 (C), 133.1 (CH), 137.7
(C), 137.9 (C), 138.1 (C), 165.3 (CO). Anal. Calcd for
C36H38O6S: C, 72.02; H, 6.4. Found: C, 72.02; H, 6.31.
4.1.8. 4-Methoxybenzyl 2-O-benzoyl-3,4,6-tri-O-benzyl-
b-D-glucopyranosyl-(1/2)-3,4-di-O-benzoyl-a-L-arabi-
nopyranoside (23). General method. In a typical experi-
ment, a mixture of alcohol 9 (3.0 g, 6.3 mmol),
˚
thioglycoside 22 (5.63 g, 9.4 mmol, 1.5 equiv), and 4 A
powdered molecular sieves (15 g) was stirred for 2 h at
room temperature in CH2Cl2 (72 mL). The mixture was
cooled to 0 8C and N-iodosuccinimide (2.12 g, 9.4 mmol,
1.5 equiv) was added followed by the dropwise addition of
triflic acid (0.028 mL, 0.05 equiv). After 2 h at 0 8C, the
reaction was quenched with triethylamine and filtered
through Celite. The filtrate was washed with NaHCO3,
10% Na2S2O3, and water. The organic layer was dried
(Na2SO4), filtered and evaporated. The crude residue was
purified by column chromatography (toluene/acetone 99:1)
to give 5.22 g (82%) of disaccharide 23 as a white
amorphous solid. RfZ0.58 (toluene/acetone 9:1). [a]D
4.1.10. 4-Methoxybenzyl 2-O-benzoyl-3,4,6-tri-O-benzyl-
b-D-glucopyranosyl-(1/4)-2,3-di-O-benzoyl-a-L-arabi-
nopyranoside (25). This compound was prepared using the
general method described for 23. Reaction of 4-methoxy-
benzyl 2,3-di-O-benzoyl-a-L-arabinopyranoside 115 (0.5 g,
1.0 mmol) and thioglycoside 22 (0.94 g, 1.6 mmol) gave
0.87 g (82%) of 25. RfZ0.56 (toluene/acetone 9:1). [a]D
1
C33.48 (c 1, CHCl3). H NMR (CDCl3): d 3.63 (m, 1H,
H-50), 3.82 (m, 4H, H-60a/b, H-30, 0 H-5a), 3.84 (s, 3H,
OCH3), 3.86 (t, 1H, JZ9.5 Hz, H-4 ), 4.17 (dd, 1H, JZ
11.3, 8.0 Hz, H-5b), 4.26 (m, 1H, H-2), 4.54 (d, 1H, JZ
11.1 Hz, CH2MPM), 4.61 (d, 1H, JZ12.1 Hz, CH2Ph), 4.64
(m, 3H, CH2Ph), 4.75 (d, 1H, JZ11.0 Hz, CH2Ph), 4.83 (d,
1H, JZ11.1 Hz, CH2MPM), 4.87 (d, 1H, JZ10.9 Hz,
CH2Ph), 4.90 (d, 1H, JZ7.9 Hz, H-10), 4.96 (d, 1H, JZ
2.6 Hz, H-1), 5.32 (m, 1H, H-4), 5.38 (t, 1H, JZ8.3 Hz,
H-20), 5.46 (m, 1H, H-3), 6.87 (d, 2H, JZ8.2 Hz, Ar-H),
7.26–7.67 (m, 26H, Ar-H), 7.85 (d, 2H, JZ7.9 Hz, Ar-H),
7.90 (d, 2H, JZ7.9 Hz, Ar-H), 7.96 (d, 2H, JZ7.8 Hz,
Ar-H). 13C NMR (CDCl3): d 55.3 (OCH3), 58.8 (C-5), 66.8
(C-4), 68.7 (C-60), 69.7 (C-3), 69.8 (CH2MPM), 73.4 (C-20),
73.6 (CH2Ph), 74.9 (C-2), 75.0 (2!CH2Ph), 75.5 (C-50),
77.8 (C-40), 82.6 (C-30), 98.9 (C-1), 100.9 (C-10), 113.7
(CH), 127.6 (CH), 127.6 (CH), 127.8 (CH), 127.8 (CH),
128.0 (CH), 128.0 (CH), 128.3 (CH), 128.3 (CH), 128.4
(CH), 129.5 (C), 129.6 (C), 129.7 (CH), 129.7 (CH), 132.9
(CH), 133.0 (CH), 133.1 (CH), 137.6 (C), 137.9 (C), 138.2
(C), 159.4 (C), 164.9 (CO), 165.1 (CO), 165.6 (CO). Anal.
1
C7.28 (c 1, CHCl3). H NMR (CDCl3): d 3.61 (m, 1H,
H-50), 3.77 (m, 2H, H-60a/b), 3.82 (m, 2H, H-30, H-40), 3.84
(s, 3H, OCH3), 3.86 (m, 1H, H-5a), 4.35 (dd, 1H, JZ11.4,
8.3 Hz, H-5b), 4.47 (m, 1H, H-4), 4.53 (d, 1H, JZ11.3 Hz,
CH2MPM), 4.62 (d, 2H, JZ12.2 Hz, CH2Ph), 4.65 (d, 1H,
JZ12.8 Hz, CH2Ph), 4.69 (d, 1H, JZ12.2 Hz, CH2Ph),
4.72 (d, 1H, JZ11.0 Hz, CH2Ph), 4.80 (d, 1H, JZ11.4 Hz,
CH2MPM), 4.81 (d, 1H, JZ7.7 Hz, H-10), 4.85 (m, 2H, H-1,
CH2Ph), 5.32 (t, 1H, JZ8.2 Hz, H-20), 5.45 (dd, 1H, JZ5.3,
3.0 Hz, H-2), 5.47 (dd, 1H, JZ5.4, 2.9 Hz, H-3), 6.82
(d, 2H, JZ8.6 Hz, Ar-H), 7.10–7.60 (m, 26H, Ar-H), 7.67
(d, 2H, JZ7.2 Hz, Ar-H), 7.87 (d, 2H, JZ7.3 Hz, Ar-H),
8.30 (d, 2H, JZ7.2 Hz, Ar-H). 13C NMR (CDCl3): d 55.2
(OCH3), 60.9 (C-5), 68.6 (C-60), 69.0 (C-2), 69.3
(CH2MPM), 69.7 (C-3), 70.7 (C-4), 73.4 (CH2Ph, C-20),
74.9 (CH2Ph), 75.0 (CH2Ph), 75.2 (C-50), 77.8 (C-40), 82.7
(C-30), 97.0 (C-1), 100.0 (C-10), 113.7 (CH), 127.6 (CH),
127.7 (CH), 127.7 (CH), 127.8 (CH), 128.0 (CH), 128.1
(CH), 128.2 (CH), 128.3 (CH), 128.4 (CH), 128.4 (CH),
129.1 (C), 129.3 (C), 129.4 (C), 129.6 (CH), 129.7 (CH),

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4355
129.8 (CH), 129.8 (CH), 159.2 (C), 164.7 (CO), 164.9 (CO),
165.4 (CO). Anal. Calcd for C61H58O14: C, 72.18; H, 5.76.
Found: C, 72.07; H, 5.80.
128.4 (CH), 128.5 (CH), 128.8 (C), 128.8 (C), 129.2 (C),
129.5 (CH), 129.5 (C), 129.6 (CH), 129.6 (CH), 129.9 (CH),
130.0 (CH), 132.9 (CH), 133.2 (CH), 133.3 (CH), 133.3
(CH), 133.4 (CH), 160.5 (C]NH), 164.6 (CO), 165.2 (CO),
165.3 (CO), 165.4 (CO), 166.1 (CO). Anal. Calcd for
C47H38Cl3NO14: C, 59.60; H, 4.04; N, 1.48. Found: C,
59.25; H, 3.93; N, 1.35.
4.1.11. 2,3,4-Tri-O-benzoyl-b-D-xylopyranosyl-(1/2)-
3,4-di-O-benzoyl-b-L-arabinopyranosyl trichloroaceti-
midate (27). General method. In a typical experiment,
trifluoroacetic acid (4.0 mL, 52.5 mmol, 20 equiv) and H20
(0.56 mL, 31.6 mmol, 12 equiv) were added to a solution of
the disaccharide 13 (2.42 g, 2.6 mmol) in CH2Cl2 (90 mL).
The reaction was vigorously stirred overnight before
being washed with H2O, NaHCO3 (satd), and NaCl (satd).
The dried solution (Na2SO4) was then evaporated under
reduced pressure and the residue taken up in CH2Cl2
(30 mL). Trichloroacetonitrile (1.3 mL, 12.8 mmol,
5 equiv) was added, followed by DBU (0.04 mL,
0.26 mmol, 0.1 equiv), and the reaction was stirred over-
night. The reaction was then evaporated and the crude
residue was purified by column chromatography (cyclo-
hexane/EtOAc/Et3N 9:1:0.1) to give 2.20 g (89%) of 27 as a
white amorphous solid. RfZ0.53 (cyclohexane/EtOAc 6:4).
4.1.13. 2,3,4-Tri-O-benzoyl-b-D-xylopyranosyl-(1/4)-
2,3-di-O-benzoyl-b-L-arabinopyranosyl trichloroaceti-
midate (29). This compound was prepared using the
general method described for 27. Deprotection of dis-
accharide 15 (0.65 g, 0.7 mmol) followed by trichloro-
acetimidate formation gave 0.56 g (83%) of 29. RfZ0.55
1
(cyclohexane/EtOAc 6:4). [a]D C50.18 (c 1, CHCl3). H
NMR (CDCl3): d 3.86 (dd, 1H, JZ12.5, 5.1 Hz, H-50), 4.28
(dd, 1H, JZ12.7, 1.5 Hz, H-5), 4.37 (brd, 1H, JZ12.7 Hz,
H-5), 4.59 (m, 2H, H-4, H-50), 5.13 (d, 1H, JZ3.8 Hz,
H-100), 5.34 (m, 1H, H-40), 5.54 (dd, 1H, JZ5.5, 4.1 Hz,
H-2 ), 5.77 (t, 1H, JZ5.7 Hz, H-30), 5.87 (dd, 1H, JZ10.7,
3.4 Hz, H-2), 5.93 (dd, 1H, JZ10.7, 2.9 Hz, H-3), 6.86 (d,
1H, JZ3.3 Hz, H-1), 7.24–7.62 (m, 15H, Ar-H), 7.90 (d,
2H, JZ7.4 Hz, Ar-H), 7.94 (d, 2H, JZ7.4 Hz, Ar-H), 7.96
(d, 2H, JZ7.4 Hz, Ar-H), 8.04 (d, 2H, JZ7.4 Hz, Ar-H),
8.18 (d, 2H, JZ7.4 Hz, Ar-H), 8.66 (s, 1H, NH). 13C NMR
(CDCl3): d 60.4 (C-50), 64.6 (C-5), 68.1 (C-2), 68.2 (C-40),
68.50(C-30), 69.4 (C-20, C-3), 74.8 (C-4), 94.2 (C-1), 100.5
(C-1 ), 128.2 (CH), 128.3 (CH), 128.3 (CH), 128.4 (CH),
128.5 (CH), 128.7 (C), 128.9 (C), 129.0 (C), 129.1 (C),
129.2 (C), 129.7 (CH), 129.7 (CH), 129.8 (CH), 130.0 (CH),
133.1 (CH), 133.2 (CH), 133.3 (CH), 133.5 (CH), 160.8
(C]NH), 164.9 (CO), 165.1 (CO), 165.2 (CO), 165.4 (CO),
165.9 (CO). Anal. Calcd for C47H38Cl3NO14: C, 59.60; H,
4.04; N, 1.48. Found: C, 59.23; H, 4.04; N, 1.58.
1
[a]D C94.68 (c 1, CHCl3). H NMR (CDCl3): d 3.81 (dd,
1H, JZ12.3, 6.7 Hz, H-50), 4.09 (dd, 1H, JZ13.2, 1.6 Hz,
H-5), 4.37 (brd, 1H, JZ12.9 Hz, H-5), 4.54 (dd, 1H, JZ
12.4, 4.4 Hz, H-50), 4.62 (dd, 1H, JZ10.4, 3.6 Hz, H-2),
5.17 (d, 1H, JZ5.4 Hz, H-10), 5.34 (m, 1H, H-40), 5.37 (dd,
1H, JZ7.8, 5.5 Hz, H-20), 5.71 (t, 1H, JZ7.5 Hz, H-30),
5.77 (dd, 1H, JZ10.4, 3.5 Hz, H-3), 5.82 (m, 1H, H-4), 6.79
(d, 1H, JZ3.5 Hz, H-1), 7.12 (t, 2H, JZ7.7 Hz, Ar-H),
7.30–7.67 (m, 15H, Ar-H), 7.80 (d, 2H, JZ8.3 Hz, Ar-H),
7.91 (d, 2H, JZ8.4 Hz, Ar-H), 8.04 (d, 2H, JZ8.4 Hz,
Ar-H), 8.08 (d, 2H, JZ8.4 Hz, Ar-H), 8.82 (s, 1H, NH). 13C
NMR (CDCl3): d 61.7 (C-50), 62.8 (C-5), 69.3 (C-3), 69.4
(C-40), 69.5 (C-4), 70.2 (C-20), 70.2 (C-30), 74.0 (C-2), 95.9
(C-1), 101.7 (C-10), 128.1 (CH), 128.3 (CH), 128.3 (CH),
128.4 (CH), 128.5 (CH), 128.8 (C), 120.0 (C), 129.1 (C),
129.5 (CH), 129.5 (CH), 129.5 (C), 129.8 (CH), 129.9 (CH),
132.9 (C), 133.1 (C), 133.3 (C), 133.4 (C), 161.1 (C]NH),
164.7 (CO), 165.1 (CO), 165.4 (CO), 165.5 (CO). Anal.
Calcd for C47H38Cl3NO14: C, 59.60; H, 4.04; N, 1.48.
Found: C, 59.45; H, 4.07; N, 1.40.
4.1.14. 2-O-Benzoyl-3,4,6-tri-O-benzyl-b-D-glucopyrano-
syl-(1/2)-3,4-di-O-benzoyl-b-L-arabinopyranosyl tri-
chloroacetimidate (30). This compound was prepared
using the general method described for 27. Deprotection
of disaccharide 23 (6.47 g, 6.4 mmol) followed by trichloro-
acetimidate formation gave 4.6 g (78%) of 30. RfZ0.64
1
4.1.12. 2,3,4-Tri-O-benzoyl-b-D-xylopyranosyl-(1/3)-
2,4-di-O-benzoyl-b-L-arabinopyranosyl trichloroaceti-
midate (28). This compound was prepared using
the general method described for 27. Deprotection of
disaccharide 14 (0.65 g, 0.7 mmol) followed by trichloro-
acetimidate formation gave 0.53 g (80%) of 28. RfZ0.55
(cyclohexane/EtOAc 6:4). [a]D C110.78 (c 1, CHCl3). H
NMR (CDCl3): d 3.68 (m, 1H, H-50), 3.77 (t, 1H, JZ9.1 Hz,
H-30), 3.84 (t, 1H, JZ9.4 Hz, H-40), 3.87 (m, 2H, H-60a/b),
4.07 (dd, 1H, JZ13.3, 1.8 Hz, H-5a), 4.31 (d, 1H, JZ
12.9 Hz, H-5b), 4.56 (m, 1H, H-2), 4.57 (d, 1H, JZ11.3 Hz,
CH2Ph), 4.66 (m, 3H, CH2Ph), 4.71 (d, 1H, JZ11.9 Hz,
CH2Ph), 4.84 (d, 1H, JZ10.8 Hz, CH2Ph), 4.87 (d, 1H, JZ
7.8 Hz, H-10), 5.25 (dd, 1H, JZ9.2, 7.9 Hz, H-20), 5.68 (dd,
1H, JZ10.4, 3.5 Hz, H-3), 3.78 (m, 1H, H-4), 6.79 (d, 1H,
JZ3.6 Hz, H-1), 7.07–7.65 (m, 25H, Ar-H), 7.74 (dd, 2H,
JZ8.3, 1.2 Hz, Ar-H), 8.05 (dd, 2H, JZ8.3, 1.3 Hz, Ar-H),
8.11 (dd, 1H, JZ8.3, 1.3 Hz, Ar-H), 8.64 (s, 1H, NH). 13C
NMR (CDCl3): d 62.7 (C-5), 68.9 (C-60), 69.4 (C-4), 69.7
(C-3), 73.0 (C-2), 73.4 (C-20), 73.7 (CH2Ph), 75.0 (CH2Ph),
75.1 (CH2Ph), 75.4 (C-50), 77.7 (C-40), 82.5 (C-30), 96.2
(C-1), 101.6 (C-10), 127.6 (CH), 127.7 (CH), 127.7 (CH),
127.9 (CH), 128.0 (CH), 128.2 (CH), 128.2 (CH), 128.4
(CH), 128.5 (CH), 129.1 (C), 129.2 (CH), 129.3 (C), 129.5
(CH), 129.6 (CH), 129.6 (C), 129.8 (CH), 132.6 (CH), 132.9
(CH), 133.0 (CH), 133.4 (CH), 137.6 (C), 137.9 (C), 138.1
(C), 161.2 (C]NH), 164.6 (CO), 164.9 (CO), 165.5 (CO).
1
(cyclohexane/EtOAc 6:4). [a]D C45.68 (c 0.5, CHCl3). H
NMR (CDCl3): d 3.81 (dd, 1H, JZ12.5, 5.7 Hz, H-50), 4.20
(dd, 1H, JZ13.4, 2.0 Hz, H-5), 4.31 (brd, 01H, JZ12.9 Hz,
H-5), 4.47 (dd, 1H, JZ12.6, 4.0 Hz, H-5 ), 4.68 (dd, 1H,
JZ10.3, 3.4 Hz, H-3), 5.26 (m, 2H, H-10, H-40), 5.34 (dd,
1H, JZ7.0, 4.8 Hz, H-20), 5.67 (t, 1H, JZ6.8 Hz, H-30),
5.78 (m, 1H, H-4), 5.85 (dd, 1H, JZ10.3, 3.6 Hz, H-2), 6.74
(d, 1H, JZ3.6 Hz, H-1), 7.17 (t, 2H, JZ7.6 Hz, Ar-H), 7.27
(t, 2H, JZ7.6 Hz, Ar-H), 7.35 (t, 2H, JZ7.7 Hz, Ar-H),
7.40–7.69 (m, 11H, Ar-H), 7.87 (d, 2H, JZ8.3 Hz, Ar-H),
7.92 (d, 2H, JZ8.4 Hz, Ar-H), 8.04 (d, 2H, JZ8.4 Hz,
Ar-H), 8.17 (d, 2H, JZ8.4 Hz, Ar-H), 8.60 (s, 1H, NH). 13C
NMR (CDCl3): d 61.2 (C-50), 63.1 (C-5), 69.0 (C-40), 69.5
(C-2), 69.7 (C-30),069.9 (C-20), 71.4 (C-4), 73.5 (C-3), 94.3
(C-1-), 101.4 (C-1 ), 128.1 (CH), 128.3 (CH), 128.3 (CH),

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4356
Anal. Calcd for C55H50Cl3NO13: C, 63.56; H, 4.85; N, 1.35.
Found: C, 63.80; H, 4.59; N, 1.30.
0.24 mmol), trichloroacetimidate 28 (0.35 g, 0.37 mmol,
˚
1.5 equiv) and 4 A powdered molecular sieves (1 g) were
stirred for 1 h at room temperature in CH2Cl2 (4 mL). The
mixture was cooled to K20 8C for 30 min followed by the
dropwise addition of a 0.1 M solution of TMSOTf in
CH2Cl2 (0.12 mL, 0.012 mmol, 0.05 equiv). After 6 h at
K20 8C the reaction was quenched with triethylamine,
filtered through Celite and evaporated. Purification by
column chromatography (toluene/acetone 99:1–98.5:1.5)
gave 0.32 g (95%) of saponin 34 as a white foam. RfZ0.63
(toluene/acetone 9:1). [a]D C53.18 (c 1, CHCl3). 1H NMR
(CDCl3): d 0.63 (s, 3H, H-24), 0.73 (s, 3H, H-26), 0.90–1.98
(m, 22H, H-1, H-2, H-5, H-6, H-7, H-9, H-11, H-15, H-16,
H-19, H-21, H-22), 0.93 (s, 3H, H-25), 0.94 (s, 3H, H-29),
0.96 (s, 3H, H-30), 1.05 (s, 3H, H-27), 2.91 (dd, 1H, JZ
13.7, 3.8 Hz, H-18), 3.56 (dd, 1H, JZ11.6, 4.7 Hz, H-3),
3.66 (dd, 1H, JZ12.5, 5.7 Hz, H-500), 3.69 (brd, 1H, JZ
13.6 Hz, H-50), 3.83 (d, 1H, JZ11.5 Hz, H-23), 4.09 (d, 1H,
JZ11.6 Hz, H-23), 4.29 (m, 2H, H-30, H-50), 4.39 (dd, 1H,
JZ12.5, 3.8 Hz, H-500), 4.55 (m, 2H, CH2CH]CH2), 4.65
(d, 1H, JZ7.1 Hz, H-10), 5.14 (d, 1H, JZ4.5 Hz, H-100),
5.19 (m, 1H, H-400), 5.23 (dd, 1H, JZ10.8, 0.8 Hz,
CH2CH]CH2), 5.27 (dd, 1H, JZ6.7, 4.7 Hz, H-200), 5.34
(m, 2H, CH2CH]CH2, H-12), 5.55 (m, 1H, H-40), 5.60
(t, 1H, JZ6.5 Hz, H-300), 5.71 (dd, 1H, JZ8.9, 7.4 Hz,
H-20), 5.92 (m, 1H, CH2CH]CH2), 7.23 (t, 2H, JZ7.7 Hz,
Ar-H), 7.30–7.65 (m, 16H, Ar-H), 7.70 (d, 2H, JZ7.6 Hz,
Ar-H), 7.94 (d, 2H, JZ7.8 Hz, Ar-H), 7.96 (d, 2H, JZ
7.6 Hz, Ar-H), 8.01 (d, 2H, JZ7.4 Hz, Ar-H), 8.04 (d, 2H,
JZ7.3 Hz, Ar-H), 8.16 (d, 2H, JZ7.4 Hz, Ar-H). 13C NMR
(CDCl3): d 12.5 (C-24), 15.5 (C-25), 16.9 (C-26), 17.9
(C-6), 22.9 (C-16), 23.4 (C-11), 23.6 (C-30), 25.3 (C-27,
C-2), 27.5 (C-15), 30.6 (C-20), 32.3 (C-7, C-22), 33.1
(C-29), 33.8 (C-21), 36.4 (C-10), 38.3 (C-1), 39.3 (C-8),
41.3 (C-18), 41.6 (C-14), 42.1 (C-4), 0045.8 (C-19), 46.7
(C-17), 48.0 (C-9), 48.1 (C-5), 60.8 (C-5 ), 63.2 (C-50), 64.8
(CH2CH]CH2), 65.3 (C-23), 68.8 (C-400), 69.5 (C-300), 69.8
(C-200), 71.0 (C-40), 71.30 (C-20), 77.1 (C-30), 83.4 (C-3),
100.7 (C-100), 103.2 (C-1 ), 117.7 (CH2CH]CH2), 122.4
(C-12), 128.0 (CH), 128.3 (CH), 128.3 (CH), 128.4 (CH),
128.6 (CH), 128.9 (C), 129.0 (C), 129.2 (C), 129.2 (C),
129.4 (CH), 129.7 (CH), 129.7 (CH), 129.8 (CH), 129.8
(CH), 130.0 (CH), 130.4 (C), 132.5 (CH2CH]CH2), 132.8
(CH), 132.9 (CH), 133.0 (CH), 133.3 (CH), 143.6 (C-13),
164.6 (CO), 164.9 (CO), 165.2 (CO), 165.4 (CO), 165.8
(CO), 166.2 (CO), 177.3 (C-28). Anal. Calcd for
C85H92O18: C, 72.84; H, 6.62. Found: C, 72.77; H, 6.85.
4.1.15. 2-O-Benzoyl-3,4,6-tri-O-benzyl-b-D-glucopyrano-
syl-(1/3)-2,4-di-O-benzoyl-b-L-arabinopyranosyl tri-
chloroacetimidate (31). This compound was prepared
using the general method described for 27. Deprotection
of disaccharide 24 (0.97 g, 1.0 mmol) followed by trichloro-
acetimidate formation gave 0.66 g (74%) of 31. RfZ0.65
1
(cyclohexane/EtOAc 6:4). [a]D C68.58 (c 1, CHCl3). H
NMR (CDCl3): d 3.66 (m, 1H, H-50), 3.77 (m, 4H, H-30,
H-40, H-60a, H-60b), 4.20 (m, 2H, H-5a, H-5b), 4.51 (d, 1H,
JZ11.9 Hz, CH2Ph), 4.56 (d, 3H, JZ11.5 Hz, CH2Ph),
4.60 (dd, 1H, JZ10.2, 3.5 Hz, H-3), 4.65 (d, 1H, JZ
11.1 Hz, CH2Ph), 4.77 (d, 1H, JZ10.8 Hz, CH2Ph), 4.93 (d,
1H, JZ7.6 Hz, H-10), 5.24 (m, 1H, H-20), 5.73 (m, 1H, H-4),
5.75 (dd, 1H, JZ10.2, 3.5 Hz, H-2), 6.65 (d, 1H, JZ3.6 Hz,
H-1), 7.06–7.62 (m, 24H, Ar-H), 7.66 (dd, 2H, JZ8.3,
1.3 Hz, Ar-H), 7.84 (dd, 2H, JZ8.4, 1.2 Hz, Ar-H), 8.15
(dd, 2H, JZ8.4, 1.4 Hz, Ar-H), 8.052 (s, 1H, NH). 13C NMR
(CDCl3): d 62.9 (C-5), 68.9 (C-6 ), 69.6 (C-2), 71.4 (C-4),
73.0 (C-3), 73.4 (C-20), 73.5 (CH2Ph), 74.7 (CH2Ph), 75.0
(CH2Ph), 75.3 (C-50), 77.6 (C-40), 82.5 (C-30), 94.2 (C-1),
101.5 (C-10), 127.5 (CH), 127.5 (CH), 127.7 (CH), 127.8
(CH), 128.0 (CH), 128.1 (CH), 128.1 (CH), 128.2 (CH),
128.3 (CH), 128.4 (CH), 128.4 (CH), 128.9 (C), 129.3 (CH),
129.4 (C), 129.6 (CH), 129.9 (C), 130.0 (CH), 132.7 (CH),
132.9 (CH), 133.1 (CH), 137.6 (C), 137.8 (C), 138.1 (C),
160.5 (C]NH), 164.6 (CO), 165.1 (CO), 166.3 (CO). Anal.
Calcd for C55H50Cl3NO13: C, 63.56; H, 4.85; N, 1.35.
Found: C, 63.17; H, 4.56; N, 1.38.
4.1.16. 2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-glucopyrano-
syl-(1/4)-2,3-di-O-benzoyl-b-L-arabinopyranosyl tri-
chloroacetimidate (32). This compound was prepared
using the general method described for 27. Deprotection
of disaccharide 25 (0.65 g, 0.6 mmol) followed by trichloro-
acetimidate formation gave 0.52 g (77%) of 32. RfZ0.63
1
(cyclohexane/EtOAc 6:4). [a]D C66.38 (c 1, CHCl3). H
NMR (CDCl3): d 3.54 (m, 1H, H-50), 3.72 (m, 2H, H-60a/b),
3.81 (m, 2H, H-30, H-40), 4.24 (d, 1H, JZ12.5 Hz, H-5a),
4.32 (dd, 1H, JZ12.6, 1.7 Hz, H-5b), 4.54 (m, 1H, H-4),
4.62 (m, 3H, CH2Ph), 4.70 (d, 1H, JZ11.0 Hz, CH2Ph),
4.77 (d, 1H, JZ11.9 Hz, CH2Ph), 4.79 (d, 1H, JZ7.9 Hz,
H-10), 4.85 (d, 1H, JZ10.9 Hz, CH2Ph), 5.47 (m, 1H, H-20),
5.78 (m, 2H, H-2, H-3), 6.79 (d, 1H, JZ1.7 Hz, H-1), 7.17–
7.54 (m, 24H, Ar-H), 7.78 (d, 2H, JZ7.3 Hz, Ar-H), 7.91
(d, 2H, JZ7.3 Hz, Ar-H), 7.97 (d, 2H, JZ7.3 Hz, Ar-H),
8.60 (s, 1H, NH0). 13C NMR (CDCl3): d 64.8 (C-5), 67.8
(C-2), 68.7 (C-6 ), 69.9 (C-3), 73.5 (CH2Ph), 73.7 (C-20),
74.8 (C-4), 75.0 (2!CH2Ph), 75.1 (C-50), 77.8 (C-40), 82.8
(C-30), 94.6 (C-1), 101.9 (C-10), 127.6 (CH), 127.7 (CH),
127.9 (CH), 128.3 (CH), 128.5 (CH), 128.8 (C), 129.1 (C),
129.5 (CH), 129.7 (CH), 129.7 (CH), 129.8 (C), 132.7 (CH),
133.1 (CH), 133.2 (CH), 137.7 (C), 137.7 (C), 137.8 (C),
138.0 (C), 160.6 (C]NH), 164.9 (CO), 165.0 (CO), 166.0
(CO). Anal. Calcd for C55H50Cl3NO13: C, 63.56; H, 4.85; N,
1.35. Found: C, 63.88; H, 5.14; N, 1.26.
4.1.18. Allyl 3-O-[2,3,4-tri-O-benzoyl-b-D-xylopyrano-
syl-(1/4)-2,3-di-O-benzoyl-a-L-arabinopyranosyl]-23-
O-benzoylhederagenate (35). This compound was pre-
pared using the general method described for 34. Reaction
of allyl hederagenate 33 (0.150 g, 0.24 mmol) and trichloro-
acetimidate 28 (0.35 g, 0.37 mmol) gave 0.178 g (94%) of
35. RfZ0.61 (toluene/acetone 9:1). [a]D C46.08 (c 1,
CHCl3). As 1H and 13C chemical shifts for the hederagenin
aglycone are nearly identical to those indicated above, only
1
selected NMR data is presented: H NMR (CDCl3): d 0.69
(s, 3H, H-24), 0.76 (s, 3H, H-26), 0.95 (s, 3H, H-29), 0.98 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.07 (s, 3H, H-27), 2.93 (dd,
1H, JZ13.6, 3.8 Hz, H-18), 3.68 (dd, 01H, JZ11.6, 4.5 Hz,
H-3), 3.77 (brd, 1H, JZ11.0 Hz, H-5 ), 3.82 (dd, 1H, JZ
12.5, 5.2 Hz, H-500), 4.02 (d, 1H, JZ11.4 Hz, H-23), 4.10 (d,
4.1.17. Allyl 3-O-[2,3,4-tri-O-benzoyl-b-D-xylopyrano-
syl-(1/3)-2,4-di-O-benzoyl-a-L-arabinopyranosyl]-23-
O-benzoylhederagenate (34). General coupling method.
In a typical experiment, allyl hederagenate 335 (0.150 g,

´
K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4357
1H, JZ11.6 Hz, H-203), 4.34 (dd, 1H, JZ12.4, 4.5 Hz, H-
50), 4.44 (m, 1H, H-4 ), 4.56 (m, 3H, H-500, CH2CH]CH2),
4.80 (d, 1H, JZ5.9 Hz, H-10), 5.08 (d, 1H, JZ4.0 Hz,
H-100), 5.25 (brd, 1H, JZ10.5 Hz, CH2CH]CH2), 5.30 (m,
1H, H-400), 5.36 (m, 2H, H-12, CH2CH]CH2), 5.42 (dd,
1H, 0 JZ5.7, 4.2 Hz, H-200), 5.45 (dd, 1H, JZ8.5, 3.2 Hz,
H-3 ), 5.72 (t, 1H, JZ5.7 Hz, H-300), 5.73 (m, 1H, H-20),
5.94 (m, 1H, CH2CH]CH2). 13C NMR (CDCl3): d 12.7
(C-24), 15.6 (C-25), 16.9 (C-26), 23.6 (C-30), 25.4 (C-27),
33.100(C-29), 60.4 (C-500), 63.5 (C-50), 65.4 (C-23), 680.5
(C-4 ), 68.9 (C-300), 69.6 (C-200), 70.0 (C-20), 71.3 (C-3 ),
73.1 (C-40), 82.4 (C-3), 99.8 (C-100), 102.3 (C-10), 122.3
(C-12), 143.6 (C-13), 177.3 (C-28). Anal. Calcd for
C85H92O18: C, 72.84; H, 6.62. Found: C, 72.70; H, 6.70.
12.0 Hz, CH2Ph), 4.73 (d, 1H, JZ11.0 Hz, CH2Ph), 4.80 (d,
1H, JZ7.5 Hz, H-100), 4.80 (m, 1H, H-10), 4.85 (d, 1H, JZ
10.9 Hz, CH2Ph), 5.25 (m, 1H, CH2CH]CH2), 5.35 (m,
2H, H-12, H-200), 5.36 (m, 1H, CH2CH]CH2), 5.38 (m, 1H,
H-30), 5.53 (dd, 1H, JZ6.7, 4.4 Hz, H-20), 5.95 (m, 1H,
CH2CH]CH2). 13C NMR (CDCl3): d 12.6 (C-24), 15.6
(C-25), 16.9 (C-26), 23.6 (C-30), 25.2 (C-2), 25.400(C-27),
33.10 (C-29), 62.0 (C-500), 65.5 (C-23), 68.6 (C-6 ), 69.8
(C-200, C-30), 71.4 (C-4 ), 73.5 (C-200), 75.2 (C-500), 770.7
(C-4 ), 82.2 (C-3), 82.7 (C-300), 100.2 (C-100), 101.0 (C-1 ),
122.4 (C-12), 143.6 (C-13), 177.3 (C-28). Anal. Calcd for
C93H104O17: C, 74.78; H, 7.02. Found: C, 74.51; H, 7.29.
4.1.21. Allyl 3-O-[2,3,4-tri-O-benzoyl-b-D-xylopyrano-
syl-(1/2)-2,3-di-O-benzoyl-b-L-arabinopyranosyl]-23-
O-benzoylhederagenate (38). This compound was pre-
pared at 0 8C using the general method described for 34.
Reaction of allyl hederagenate 33 (0.26 g, 0.41 mmol) and
trichloroacetimidate 27 (0.59 g, 0.62 mmol) gave 0.55 g
(94%) of 38. RfZ0.62 (toluene/acetone 9:1). [a]D C81.98
(c 1, CHCl3). Selected NMR data: 1H NMR (CDCl3): d 0.83
(s, 3H, H-26), 0.96 (s, 6H, H-24, H-29), 0.99 (s, 3H, H-30),
1.10 (s, 3H, H-25), 1.13 (s, 3H, H-27), 2.96 (dd, 1H, JZ
14.2, 3.7 Hz, H-18), 3.72 (dd, 1H, JZ11.9, 8.3 Hz, H-500),
3.82 (brd, 1H, JZ13.0 Hz, H-50), 3.88 (dd0, 1H, JZ11.7,
4.3 Hz, H-3), 4.20 (brd, 1H, JZ12.7 Hz, H-05 ), 4.33 (m, 2H,
H-23), 4.39 (dd, 1H, 0J0 Z10.4, 3.5 Hz, H-2 ), 4.49 (dd, 1H,
JZ11.9, 4.8 Hz, H-5 ), 4.60 (m, 2H, CH2CH]CH2), 5.06
(d, 1H, JZ6.2 Hz, H-100), 5.28 (dd,0 1H, JZ00 10.5, 1.0 Hz,
CH2CH]CH2), 5.39 (m, 6H, H-1 , H-2 , H-400, H-12,
CH2CH]CH2), 5.62 (dd, 1H, JZ10.5, 3.5 Hz, H-30), 5.69
(m, 1H, H-40), 5.74 (t, 1H, JZ8.4 Hz, H-300), 5.97 (m, 1H,
CH2CH]CH2). 13C NMR (CDCl3): d 13.1 (C-24), 15.8
(C-25), 17.0 (C-26), 21.8 (C-2), 23.6 (C-30), 25.5 (C-27),
33.10 (C-29), 61.0 (C-50), 62.2 (C-500), 66.0 (C-23), 69.6
(C-3 ), 69.7 (C-400), 70.2 (C-40), 70.8 (C-200), 71.1 (C-300),
74.8 (C-20), 78.8 (C-3), 96.7 (C-10), 102.0 (C-100), 122.4
(C-12), 143.6 (C-13), 177.3 (C-28). Anal. Calcd for
C85H92O18: C, 72.84; H, 6.62. Found: C, 72.45; H, 6.43.
4.1.19. Allyl 3-O-[2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-
glucopyranosyl-(1/3)-2,4-di-O-benzoyl-a-L-arabino-
pyranosyl]-23-O-benzoylhederagenate (36). This com-
pound was prepared using the general method described
for 34. Reaction of allyl hederagenate 33 (0.31 g,
0.51 mmol) and trichloroacetimidate 31 (0.79 g,
0.76 mmol) gave 0.71 g (93%) of 36. RfZ0.72 (toluene/
acetone 9:1). [a]D C69.08 (c 1, CHCl3). Selected NMR
1
data: H NMR (CDCl3): d 0.55 (s, 3H, H-24), 0.72 (s, 3H,
H-26), 0.91 (s, 3H, H-25), 0.94 (s, 3H, H-29), 0.97 (s, 3H,
H-30), 1.04 (s, 3H, H-27), 2.91 (dd, 1H, JZ13.6, 3.8 Hz,
H-18), 3.53 (dd, 1H, JZ11.6, 4.8 Hz, H-3), 3.58 (m, 1H,
H-500), 3.59 (dl, 1H, JZ12.7 Hz, H-5a000), 3.69 (m, 2H, H-300,
H-400), 3.75 (m, 3H, H-23a, H-6a/b ), 3.96 (d, 1H, JZ
11.5 Hz, H-23b), 4.19 (dd, 1H, JZ9.9, JZ3.7 Hz, H-30),
4.28 (dd, 1H, JZ13.4, 1.8 Hz, H-5b0), 4.54 (m, 7H, H-10,
CH2Ph, CH2CH]CH2), 4.61 (d, 1H, JZ11.0 Hz, CH2Ph),
4.78 (d, 1H, JZ10.8 Hz, CH2Ph), 4.79 (d, 1H, JZ7.7 Hz,
H-100), 5.20 (m, 1H, H-200), 5.23 (m, 1H, CH2CH]CH2),
5.32 (m, 1H, H-12), 5.34 (m, 1H, CH2CH]CH2), 5.51 (m,
1H, H-40), 5.62 (dd, 1H, JZ9.8, 7.8 Hz, H-20), 5.92 (m, 1H,
CH2CH]CH2). 13C NMR (CDCl3): d 12.5 (C-24), 15.5
(C-25), 16.9 (C-26), 23.6 (C-30), 25.3 (C-27), 25.4 (C-2),
33.10 (C-29), 64.0 (C-50), 65.3 (C-23), 69.0 (C-600), 710.6
(C-4 ), 710.07 (C-20), 73.4 (C-200), 75.1 (C-500), 76.060 (C-3 ),
77.60(C-4 ), 82.1 (C-3), 82.7 (C-300), 101.4 (C-1 ), 103.4
(C-1 ), 122.4 (C-12), 143.6 (C-13), 177.3 (C-28). Anal.
Calcd for C93H104O17 ($0.9 CH3OH): C, 74.07; H, 7.12.
Found: C, 73.91; H, 7.12.
4.1.22. Allyl 3-O-[2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-
glucopyranosyl-(1/2)-3,4-di-O-benzoyl-b-L-arabino-
pyranosyl]-23-O-benzoylhederagenate (39). This com-
pound was prepared at 0 8C using the general method
described for 34. Reaction of allyl hederagenate 33
(0.40 g, 0.65 mmol) and trichloroacetimidate 30 (1.01 g,
0.97 mmol) gave 0.82 g (85%) of 39. RfZ0.75 (toluene/
acetone 9:1). [a]D C83.38 (c 1, CHCl3). Selected NMR
4.1.20. Allyl 3-O-[2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-
glucopyranosyl-(1/4)-2,3-di-O-benzoyl-a-L-arabino-
pyranosyl]-23-O-benzoylhederagenate (37). This com-
pound was prepared using the general method described
for 34. Reaction of allyl hederagenate 33 (0.11 g,
0.18 mmol) and trichloroacetimidate 32 (0.28 g,
0.27 mmol) gave 0.25 g (95%) of 37. RfZ0.70 (toluene/
acetone 9:1). [a]D C50.08 (c 1, CHCl3). Selected NMR
1
data: H NMR (CDCl3): d 0.81 (s, 3H, H-26), 0.94 (s, 3H,
H-24), 0.97 (s, 3H, H-29), 1.01 (s, 3H, H-30), 1.04 (s, 3H,
H-25), 1.12 (s, 3H, H-27), 2.96 (dd, 1H, JZ13.4, 3.3 Hz,
H-18), 3.65 (m, 1H, H-500), 3.76 (m, 1H, H-3), 3.77 (t, 1H,
JZ9.2 Hz, H-300), 3.82 (m, 1H, H-5a0), 3.84 (m, 2H, H-6a/
b00), 3.89 (t, 1H, JZ9.2 Hz, H-400), 4.23 (dl, 1H, JZ12.6 Hz,
H-5b0), 4.27 (d, 1H, JZ11.5 Hz, H-23a), 4.31 (d, 1H, JZ
11.5 Hz, H-23b), 4.37 (dd, 1H, JZ10.5, 3.6 Hz, H-20), 4.56
(d, 1H, JZ12.0 Hz, CH2Ph), 4.58 (d, 1H, JZ10.9 Hz,
CH2Ph), 4.61 (m, 2H, CH2CH]CH2), 4.65 (d, 1H, JZ
11.0 Hz, CH2Ph), 4.68 (d, 2H, JZ11.5 Hz, CH2Ph), 4.85 (d,
1H, JZ7.8 Hz, H-100), 4.87 (d, 1H, JZ10.8 Hz, CH2Ph),
5.29 (m, 2H, H-200, CH2CH]CH2), 5.39 (m, 2H, H-10,
CH2CH]CH2), 5.53 (dd, 1H, JZ10.5, 3.5 Hz, H-30), 5.67
(m, 1H, H-40), 5.97 (m, 1H, CH2CH]CH2). 13C NMR
1
data: H NMR (CDCl3): d 0.58 (s, 3H, H-24), 0.75 (s, 3H,
H-26), 0.95 (s, 3H, H-29), 0.96 (s, 3H, H-25), 0.98 (s, 3H,
H-30), 1.05 (s, 3H, H-27), 2.93 (dd, 1H, JZ13.3, 3.1 Hz,
H-18), 3.55 (m, 1H, H-500), 3.63 (dd, 1H, JZ11.7, 4.5 Hz,
H-3), 3.74 (m,002H, H-6a/b00), 3.76 (m, 1H, H-5a0), 3.80 (m,
2H, H-300, H-4 ), 4.01 (d, 1H, JZ11.5 Hz, H-23a), 4.07 (d,
1H, JZ11.5 Hz, H-23b), 0 4.36 (dd, 1H, JZ11.8, 6.7 Hz,
H-5b0), 4.45 (m, 1H, H-4 ), 4.57 (m, 2H, CH2CH]CH2),
4.60 (d, 1H, JZ12.3 Hz, CH2Ph), 4.62 (d, 1H, JZ10.9 Hz,
CH2Ph), 4.65 (d, 1H, JZ9.0 Hz, CH2Ph), 4.67 (d, 1H, JZ

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K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4358
(CDCl3): d 13.1 (C-24), 15.7 (C-25), 17.0 (C-26), 22.0
(C-2), 23.6 (C-30), 25.4 (C-27), 33.10 (C-29), 61.00 (C-50),
66.30 (C-23), 68.8 (C-600), 70.0 (C-3 ), 70.030 (C-4 ), 73.6
(C-2 ), 73.7 (C-200), 75.1 (C-500), 77.8 (C-4 ), 79.6 (C-3),
82.7 (C-300), 97.4 (C-10), 101.6 (C-100), 122.5 (C-12), 143.5
(C-13), 177.3 (C-28). Anal. Calcd for C93H104O17: C, 74.78;
H, 7.02. Found: C, 74.44; H, 7.20.
9.2 Hz, H-400), 4.20 (dd, 1H, JZ12.0, 6.4 Hz, H-5b0), 4.27
(d, 1H, JZ11.4 Hz, H-23a), 4.32 (m, 2H, H-20, H-23b), 4.57
(m, 4H, CH2CH]CH2, CH2Ph), 4.60 (m, 2H, CH2Ph), 4.69
(d, 1H, JZ11.2 Hz, CH2Ph), 4.82 (m, 1H, H-10), 4.83 (d,
1H, JZ10.8 Hz, CH2Ph), 4.89 (d, 1H, JZ8.0 Hz, H-100),
5.25 (m, 2H, H-30, CH2CH]CH2), 5.31 (dd, 1H, JZ9.4,
8.1 Hz, H-200), 4.35 (m, 1H, H-12), 4.36 (m, 1H, CH2CHZ
]CH2), 4.38 (m, 1H, H-40), 5.95 (m, 1H, CH2CH]CH2).
13C NMR (CDCl3): d 12.8 (C-24), 15.6 (C-25), 17.0 (C-26),
23.60 (C-30), 25.1 (C-2), 25.40 (C-27), 33.010 (C-29), 600.2
(C-5 ), 65.9 (C-23), 67.04 (C-4 ), 69.1 (C-6 ), 71.8 (C-3 ),
73.400(C-200), 74.7 (C-2 ), 75.5 (C-500), 770.8 (C-400), 82.7
(C-3 ), 82.8 (C-3), 101.4 (C-100), 101.9 (C-1 ), 122.3 (C-12),
143.7 (C-13), 177.3 (C-28). Anal. Calcd for C93H104O17: C,
74.78; H, 7.02. Found: C, 74.44; H, 7.31.
4.1.23. Allyl 3-O-[2,3,4-tri-O-benzoyl-b-D-xylopyrano-
syl-(1/2)-2,3-di-O-benzoyl-a-L-arabinopyranosyl]-23-
O-benzoylhederagenate (40). Allyl hederagenate 33 (0.8 g,
1.3 mmol), trichloroacetimidate 27 (2.46 g, 2.6 mmol,
˚
2.0 equiv) and 4 A powdered molecular sieves (7 g) were
stirred for 1 h at room temperature in dry acetonitrile
(20 mL). The mixture was cooled to K35 8C for 30 min
followed by the rapid addition of a 0.1 M solution of
TMSOTf in acetonitrile (3.9 mL, 0.39 mmol, 0.3 equiv).
The reaction was stirred at this temperature until tlc
indicated the disappearance of the allyl hederagenin.
Triethylamine was added and the mixture was filtered
through Celite and evaporated. The crude residue was
purified by column chromatography (toluene/acetone 99:1)
to give 0.68 g (38%) of the desired a anomer, and 0.48 g of a
mixture of anomeric products. HPLC separation (100%
acetonitrile) gave a further 0.36 g (20%) of the desired
saponin 40 as a white foam (total yield 58%), and 0.12 g
(6%) of the b anomer 38 which was previously described
above. RfZ0.63 (toluene/acetone 9:1). [a]D C47.18 (c 1,
4.1.25. 3-O-[b-D-xylopyranosyl-(1/2)-a-L-arabinopyra-
nosyl]hederagenin (1). General method 1. In a typical
experiment, Pd(PPh3)4 (0.57 g, 0.49 mmol, 1.0 equiv) was
added to a solution of saponin 40 (0.680 g, 0.49 mmol) in
3% KOH in MeOH (39 mL). After heating to 60 8C for 6 h,
the reaction was neutralized with Amberlite IR 120 (HC
form), filtered and evaporated. The crude residue was
purified by column chromatography (CH2Cl2/MeOH 9:1–
8:2) to give 0.280 g (76%) of the deprotected saponin 1 as
an amorphous solid.
General method 2. Use of a catalytic amount of Pd(PPh3)4:
in a typical experiment Pd(PPh3)4 (0.025 g, 0.02 mmol,
0.3 equiv) was added to a solution of saponin 40 (0.102 g,
0.07 mmol) in a THF/3% KOH in MeOH (1:1) mixture
(6 mL). After heating to 60 8C for 7 h, the reaction was
neutralized with Amberlite IR 120 (HC form), filtered and
evaporated. The crude residue was purified by column
chromatography (CH2Cl2/MeOH 9:1–8:2) to give 0.048 g
(89%) of the deprotected saponin 1 as an amorphous solid.
1
CHCl3). Selected NMR data: H NMR (CDCl3): d 0.77 (s,
3H, H-24), 0.79 (s, 3H, H-26), 0.96 (s, 3H, H-29), 0.98 (s,
3H, H-30), 1.02 (s, 3H, H-25), 1.13 (s, 3H, H-27), 2.94 (dd,
1H, 0J0 Z13.7, 3.8 Hz, H-18), 3.66 (dd, 1H, JZ12.0, 7.8 Hz,
H-5 ), 3.73 (dd, 1H, JZ11.6, 4.4 Hz, H-3), 3.84 (dd, 1H,
JZ11.6, 3.2 Hz, H-50), 4.20 (d, 1H, JZ11.4 Hz, H-23), 4.27
(dd, 1H, JZ11.7, 7.1 Hz, H-50), 4.34 (dd, 1H, JZ6.0,
3.9 Hz, H-2000), 4.37 (m, 1H, H-23), 4.41 (dd, 1H, JZ12.1,
4.4 Hz, H-5 ), 4.58 (m, 2H, CH2CH]CH2), 4.89 (d, 1H,
JZ3.5 Hz, H-10), 5.14 (d, 1H, JZ5.9 Hz, H-100), 5.26 (d,
1H, JZ10.5 Hz, CH2CH]CH2), 5.32 (m, 1H, H-400), 5.37
(m, 3H, H-12, H-30, CH2CH]CH2), 5.44 (dd, 1H, JZ7.7,
6.1 Hz, H-200), 5.48 (m, 1H, H-40), 5.74 (t, 1H, JZ7.8 Hz,
H-300), 5.95 (m, 1H, CH2CH]CH2). 13C NMR (CDCl3): d
12.7 (C-24), 15.8 (C-25), 17.0 (C-26), 23.6 (C-30), 25.2
(C-2), 25.4 (C-27), 33.1 (C-29), 59.4 (C-50), 61.700 (C-500),
65.7 (C-23), 67.1 (C-40), 69.2 (C-400), 70.7 (C-3 , C-200,
C-30), 75.1 (C-20), 82.9 (C-3), 101.0 (C-100), 101.9 (C-10),
122.3 (C-12), 143.7 (C-13), 177.3 (C-28). Anal. Calcd for
C85H92O18: C, 72.84; H, 6.62. Found: C, 72.69; H, 6.84.
1
[a]D C41.08 (c 0.5, pyridine). H NMR (pyridine-d5): d
0.90 (s, 3H, H-29), 0.93 (s, 3H, H-25), 0.98 (s, 3H, H-30),
1.00 (s, 6H, H-24, H-26), 1.03–2.22 (m, 22H, H-1, H-2, H-5,
H-6, H-7, H-9, H-11, H-15, H-16, H-19, H-21, H-22), 1.22
(s, 3H, H-270)0, 3.26 (dd, 1H, JZ13.6, 3.8 Hz, H-18), 3.56
(m, 1H, H-5 ), 3.64 (brd, 1H, JZ11.1 Hz0,0 H-50), 3.68 (d,
1H, 00JZ11.0 Hz, H-23), 4.08 (m, 1H, H-20 ), 4.10 (m, 1H,
H-300), 4.15 (dd, 1H, JZ8.4, 2.3 Hz, H-3 ), 4.18 (m, 1H,
H-4 ), 4.24 (m, 1H, H-50), 4.25 (m, 1H, H-40), 4.27 (m, 1H,
H-3), 4.31 (dd, 1H, JZ11.4, 5.2 Hz, H-500), 4.035 (d, 1H, JZ
11.1 Hz, H-23), 4.53 (brt, 1H, JZ7.5 Hz, H-2 ), 5.07 (d, 1H,
JZ6.5 Hz, H-100), 5.11 (d, 1H, JZ6.6 Hz, H-10), 5.46
(m, 1H, H-12). 13C NMR (pyridine-d5): d 12.9 (C-24), 15.8
(C-25), 17.1 (C-26), 17.8 (C-6), 23.3 (C-16), 23.4 (C-30),
23.5 (C-11), 25.9 (C-27), 26.0 (C-2), 28.0 (C-15), 30.6
(C-20), 32.5 (C-7), 32.9 (C-22, C-29), 33.8 (C-21), 36.6
(C-10), 38.5 (C-1), 39.4 (C-8), 41.6 (C-18), 41.8 (C-14),
43.3 (C-4), 46.1 (C-19), 46.3 (C-17), 47.0 (C-5), 47.8 (C-9),
63.200(C-23), 65.6 (C-50), 67.1 (C-500), 68.4 (C-40), 70.6
(C-4 ), 73.6 (C-30), 75.8 (C-200), 77.9 (C-300), 81.1 (C-3),
81.5 (C-20), 104.2 (C-10), 106.4 (C-100), 122.3 (C-12), 144.5
(C-13), 179.9 (C-28). HRMS: C40H64O12Na calcd
759.4295; found 759.4316.
4.1.24. Allyl 3-O-[2-O-benzoyl-3,4,6-tri-O-benzyl-b-D-
glucopyranosyl-(1/2)-3,4-di-O-benzoyl-a-L-arabino-
pyranosyl]-23-O-benzoylhederagenate (41). This product
was prepared in acetonitrile as described for compound 40.
Reaction of allyl hederagenate 33 (0.83 g, 1.3 mmol) and
trichloroacetimidate 30 (2.8 g, 2.7 mmol) gave 1.22 g
(61%) of 41 as well as 0.28 g (14%) of the b coupling
product 39. RfZ0.69 (toluene/acetone 9:1). [a]D C47.58 (c
1, CHCl3). 1H NMR (CDCl3): d 0.73 (s, 3H, H-24), 0.76 (s,
3H, H-26), 0.95 (s, 3H, H-29), 0.97 (s, 3H, H-25), 0.98 (s,
3H, H-30), 1.07 (s, 3H, H-27), 2.92 (dd, 1H, JZ13.7,
3.8 Hz, H-18), 3.64 (dt, JZ9.7, 3.3 Hz, H-500), 3.69 (dd, 1H,
JZ11.7, 4.6 Hz, H-3), 3.75 (t, 1H, JZ9.2 Hz, H-300), 3.78
(m, 1H, H-5a0), 3.80 (m, 2H, H-6a/b00), 3.85 (t, 1H, JZ
4.1.26. 3-O-[b-D-xylopyranosyl-(1/2)-b-L-arabinopyra-
nosyl]hederagenin (2). Using a stoichiometric amount of

´
K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4359
Pd(PPh3)4 in the general deprotection method 1 described
for 1, the deprotection of saponin 38 (0.52 g, 0.37 mmol)
gave 0.17 g (64%) of 2. Use of the catalytic method with
0.115 g (0.08 mmol) of 38 gave 0.050 g (84%) of 2. [a]D
H-30), 4.20 (m, 1H, H-400), 4.23 (dd, 1H, JZ12.2, 4.6 Hz,
H-3), 4.26 (brd, 1H, JZ11.1 Hz, H-23), 4.27 (m, 1H, H-40),
4.30 (dd, 1H, JZ11.3, 5.2 Hz, H-500), 4.40 (dd, 1H, JZ9.1,
7.4 Hz, H-20), 4.43 (0dd, 1H, JZ12.5, 2.2 Hz, H-50), 4.96 (d,
1H, JZ7.3 Hz, H-1 ), 5.06 (d, 1H, JZ7.7 Hz, H-100), 5.47
(m, 1H, H-12). 13C NMR (pyridine-d5): d 13.3 (C-24), 15.8
(C-25), 17.2 (C-26), 23.5 (C-30), 25.9 (C-27), 33.000(C-29),
63.90 (C-23), 66.0 (C-50), 66.9 (C-500), 70.5 (C-4 ), 730.1
(C-2 ), 74.0 (C-30), 75.0 (C-200), 770.08 (C-300), 79.2 (C-4 ),
81.8 (C-3), 106.1 (C-10), 106.8 (C-1 ), 122.3 (C-12), 144.5
(C-13), 180.1 (C-28). HRMS: C40H64O12Na calcd
759.4295; found 759.4266.
1
C82.28 (c 0.5, pyridine). Selected NMR data: H NMR
(pyridine-d5): d 0.85 (s, 3H, H-24), 0.85 (s, 3H, H-25), 0.92
(s, 3H, H-29), 0.99 (s, 3H, H-30), 1.00 (s, 3H, H-26), 1.24
(s, 3H, H-27), 3.27 (dd, 1H, JZ13.5, 3.6 Hz, H-18), 3.50
(dd, 1H, JZ11.0, 10.1 Hz, H-500), 3.70 (d, 1H, JZ10.7 Hz,
H-23), 3.93 (d, 1H, JZ10.9 Hz, H-23), 4.10 (dd, 1H, JZ
8.7, 7.0 Hz, H-200), 004.12 (dd, 1H, JZ10.5, 1.7 Hz, H-50; t,
1H, JZ8.6 Hz, H-3 ), 4.18 (m, 1H, H-400), 4.21 (dd, 1H, JZ
11.9, 4.8 Hz, H-3), 4.25 (dd, 1H, JZ11.3, 5.1 Hz,0 H-500),
4.43 (m, 1H, H-40), 4.44 (brd, 1H, JZ11.3 Hz, H-5 ), 4.62
(dd,01H, JZ9.9, 3.1 Hz, H-30), 4.67 (dd, 1H, JZ9.9, 3.2 Hz,
H-2 ), 5.00 (d, 1H, JZ7.1 Hz, H-100), 5.48 (m, 1H, H-12),
5.69 (d, 1H, JZ3.3 Hz, H-10). 13C NMR (pyridine-d5): d
13.8 (C-24), 15.6 (C-25), 17.2 (C-26), 22.2 (C-2), 230.5
(C-30), 25.9 (C-27), 33.00 (C-29), 64.0 (C-23), 64.3 (C-5 ),
66.600(C-500), 69.2 (C-3 ), 70.0 (C-40), 70.5 (C-400), 740.8
(C-2 ), 77.4 (C-3), 77.5 (C-300), 79.4 (C-20), 97.6 (C-1 ),
106.6 (C-100), 122.3 (C-12), 144.6 (C-13), 180.3 (C-28).
HRMS: C40H64O12Na calcd 759.4295; found 759.4275.
4.1.29. 3-O-[b-D-glucopyranosyl-(1/2)-a-L-arabinopyr-
anosyl]hederagenin (5). General method 1. In a typical
experiment, Pd(PPh3)4 (0.57 g, 0.49 mmol, 1.0 equiv) was
added to a solution of saponin 41 (0.730 g, 0.49 mmol) in
3% KOH in MeOH (39 mL). After heating to 60 8C for 6 h,
the reaction was neutralized with Amberlite IR 120 (HC
form), filtered and evaporated. The crude residue was taken
up in ethanol (84 mL) and Pd/C (2.51 g) was added. The
reaction then was placed under H2. After stirring for 48 h
at room temperature, the mixture was filtered over celite,
evaporated, and the crude saponin purified by column
chromatography (CH2Cl2/MeOH 9:1–8:2) to give 0.37 g
(82%) of the desired product 5 as an amorphous solid.
4.1.27. 3-O-[b-D-xylopyranosyl-(1/3)-a-L-arabinopyra-
nosyl]hederagenin (3). Using a stoichiometric amount of
Pd(PPh3)4 in the general deprotection method 1 described
for 1, the deprotection of saponin 34 (0.26 g, 0.18 mmol)
gave 0.11 g (82%) of 3. Use of the catalytic method with
0.055 g (0.04 mmol) of 34 gave 0.021 g (72%) of 3. [a]D
General method 2. Use of a catalytic amount of Pd(PPh3)4:
in a typical experiment Pd(PPh3)4 (0.031 g, 0.03 mmol,
0.3 equiv) was added to a solution of saponin 41 (0.132 g,
0.09 mmol) in a THF/3% KOH in MeOH (1:1) mixture
(6 mL). After heating to 60 8C for 7 h, the reaction was
neutralized with Amberlite IR 120 (HC form), filtered and
evaporated. The crude residue was rapidly passed through a
silica gel column to remove non-polar impurities (CH2Cl2/
MeOH, 9.8:0.2) and the partially protected saponin was
taken up in ethanol (7 mL) and Pd/C (0.080 g) was added.
The reaction then was placed under H2. After stirring for
24–48 h at room temperature, the mixture was filtered over
celite, evaporated, and the crude saponin purified by column
chromatography (CHCl3/MeOH 9:1–8:2) to give 0.059 g
(87%) of the desired product 5 as an amorphous solid.
1H NMR (pyridine-d5): d 0.89 (s, 3H, H-25), 0.91 (s, 3H,
H-29), 0.97 (s, 6H, H-30, H-26), 0.98–2.15 (m, 22H, H-1,
H-2, H-5, H-6, H-7, H-9, H-11, H-15, H-16, H-19, H-21,
H-22), 1.00 (s, 3H, H-24), 1.20 (s, 3H, H-27), 3.27 (dd, 1H,
JZ13.6, 3.7 Hz, H-18), 3.70 (brd, 1H, JZ10.7 Hz,00H-5a0),
3.73 (d, 1H, JZ10.8 Hz, H-23a), 3.81 (m, 1H, H-5 ), 4.09
(t, 1H, JZ8.0 Hz, H-200), 4.16 (dd, 1H, JZ7.5, 4.5 Hz, H-3),
4.18 (t, 1H, JZ8.1 Hz, H-300), 4.22 (m, 2H, H-23b, H-4000),
4.27 (dd, 1H, JZ7.0, 3.7 Hz, H-30), 4.28 (m, 1H, H-5b ),
4.32 (m, 1H, H-40), 4.35 (dd, 1H, JZ11.7, 4.5 Hz, H-6a00),
4.47 (dd, 1H, JZ11.7, 1.6 Hz, H-6b00), 4.060 (t, 1H, JZ
6.7 Hz, H-20), 5.19 (d, 1H, JZ4.6 Hz, H-1 ), 5.20 (d, 1H,
JZ7.0 Hz, H-100), 5.45 (m, 1H, H-12). 13C NMR (pyridine-
d5): d 13.2 (C-24), 15.7 (C-25), 17.2 (C-26), 17.8 (C-6), 23.4
(C-16), 23.5 (C-30), 23.5 (C-11), 25.7 (C-2), 25.8 (C-27),
28.0 (C-15), 30.6 (C-20), 32.5 (C-7), 32.9 (C-22), 33.0
(C-29), 34.9 (C-21), 36.6 (C-10), 38.3 (C-1), 39.4 (C-8),
41.6 (C-18), 41.8 (C-14), 43.2 (C-4), 46.3 (C-19), 46.3
(C-17), 47.4 (C-5), 47.8 (C-9), 62.100(C-600), 64.3 0(C-23),
64.800(C-50), 67.900 (C-40), 71.000 (C-4 ), 73.2 (C-3 ), 75.8
(C-2 ), 77.7 (C-3 ), 78.0 (C-5 ), 80.7 (C-20), 81.8 (C-3),
1
C47.68 (c 0.5, pyridine). Selected NMR data: H NMR
(pyridine-d5): d 0.91 (s, 3H, H-25), 0.92 (s, 3H, H-24), 0.92
(s, 3H, H-29), 0.98 (s, 3H, H-30), 1.00 (s, 3H, H-26), 1.24
(s, 3H, H-27), 3.27 (dd, 1H, JZ13.7, 3.7 Hz, H-18), 3.70
(d, 1H, JZ10.7 Hz, H-23), 3.71 (m, 1H, H-500), 3.75 (brd,
1H, JZ11.6 Hz, H-50), 4.03 (dd, 1H, JZ8.8, 7.7 Hz, H-200),
4.10 (dd, 1H, JZ9.4, 3.3 Hz, H-30), 4.18 (m, 2H, H-300,
H-400), 4.26 (dd, 1H, JZ12.0, 2.0 Hz, H-50), 4.29 (dd, 1H,
JZ12.2, 4.6 Hz, H-3), 4.32 (d, 010 H, JZ10.6 Hz, H-23), 4.33
(dd, 1H, JZ10.7, 5.2 Hz, H-50 ), 4.39 (m, 1H, H-40), 4.59
(dd,0 1H, JZ9.2, 7.7 Hz, H-2 ), 5.04 (d, 1H, JZ7.5 Hz,
H-1 ), 5.20 (d, 1H, JZ7.6 Hz, H-100), 5.47 (m, 1H, H-12).
13C NMR (pyridine-d5): d 13.4 (C-24), 15.8 (C-25), 17.2
(C-26), 23.5 (C-30), 25.9 (C-27), 33.0 (C-29), 63.600(C-23),
66.70 (C-50), 66.800 (C-500), 69.0 (C-40), 70.6 (C-4 ), 710.5
(C-2 ), 74.9 (C-2 ), 77.5 0(0 C-300), 81.5 (C-3), 83.3 (C-3 ),
106.2 (C-10), 106.3 (C-1 ), 122.3 (C-12), 144.5 (C-13),
180.2 (C-28). HRMS: C40H64O12Na calcd 759.4295; found
759.4303.
4.1.28. 3-O-[b-D-xylopyranosyl-(1/4)-a-L-arabinopyra-
nosyl]hederagenin (4). Using a stoichiometric amount of
Pd(PPh3)4 in the general deprotection method 1 described
for 1, the deprotection of saponin 35 (0.32 g, 0.23 mmol)
gave 0.14 g (84%) of 4. Use of the catalytic method with
0.108 g (0.08 mmol) of 35 gave 0.042 g (74%) of 4. [a]D
1
C46.88 (c 0.5, pyridine). Selected NMR data: H NMR
(pyridine-d5): d 0.88 (s, 3H, H-24), 0.92 (s, 6H, H-25, H-29),
0.98 (s, 3H, H-30), 0.99 (s, 3H, H-26), 1.23 (s, 3H, H-27),
3.27 (dd, 1H, JZ13.7, 3.8 Hz, H-18), 3.64 (brt, 1H, JZ
10.6 Hz, H-500), 3.670(d, 1H, JZ10.7 Hz, H-23), 3.76 (brd,
1H, JZ11.6 Hz, H-5 ), 4.02 (dd, 1H, JZ8.7, 7.9 Hz, H-200),
4.13 (t, 1H, JZ8.8 Hz, H-300), 4.15 (dd, 1H, JZ9.3, 3.6 Hz,

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103.7 (C-10), 105.4 (C-100), 122.2 (C-12), 144.6 (C-13).
HRMS: C41H66O13Na calcd 789.4401; found 789.4415.
(s, 3H, H-25), 0.98 (s, 3H, H-30), 0.99 (s, 3H, H-26), 1.23 (s,
3H, H-27), 3.27 (dd, 1H, JZ13.6, 3.6 Hz, H-18), 3.67 (0d,
1H, JZ10.6 Hz, H-23a), 3.68 (brd, 1H, JZ11.8 Hz, H-5a ),
3.94 (m, 1H, H-500), 4.05 (m, 1H, H-200), 4.10 (dd, 1H, JZ
9.2,003.4 Hz, H-30), 4.21 (m, 1H, H-3), 4.22 (m, 2H, H-300,
H-4 ), 4.27 (d, 1H, JZ11.0 Hz, H-23b), 4.32 (m, 1H, H-40),
4.35 (dd, 1H, JZ12.0, 5.3 Hz, H-6a00), 4.41 (dd, 1H, JZ8.9,
7.6 Hz, H-20), 4.44 (m, 1H, H-5b0), 4.51 (dd, 1H, JZ11.9,
1.8 Hz, H-6b00), 4.94 (d, 1H, JZ7.3 Hz, H-10), 5.23 (d, 1H,
JZ7.8 Hz, H-100), 5.44 (m, 1H, H-12). 13C NMR (pyridine-
d5): d 13.3 (C-24), 15.8 (C-25), 17.2 (C-26), 23.5 (C-30),
25.8 (C-2), 25.9 (C-27), 33.0 (C-29), 62.1 (C-600), 630.9
(C-23), 66.0 (C-50), 70.090 (C-400), 73.2 (C-20), 74.20 (C-3 ),
75.3 (C-200), 77.9 (C-3 ), 78.3 (C-500), 79.4 (C-4 ), 81.8
(C-3), 106.1 (C-10), 106.4 (C-100), 122.2 (C-12), 144.6
(C-13). HRMS: C41H66O13Na calcd 789.4401; found
789.4409.
4.1.30. 3-O-[b-D-glucopyranosyl-(1/2)-b-L-arabinopyr-
anosyl]hederagenin (6). Using a stoichiometric amount of
Pd(PPh3)4 in the general deprotection method 1 described
for 5, the deprotection of saponin 39 (0.89 g, 0.60 mmol)
gave 0.40 g (88%) of 6. Use of the catalytic method with
0.145 g (0.10 mmol) of 39 gave 0.061 g (82%) of 6. [a]D
1
C74.68 (c 0.5, pyridine). Selected NMR data: H NMR
(pyridine-d5): d 0.83 (s, 3H, H-25), 0.85 (s, 3H, H-24), 0.92
(s, 3H, H-29), 0.98 (s, 6H, H-26, H-30), 1.20 (s, 3H, H-27),
3.27 (dd, 1H, JZ13.7, 3.6 Hz, H-18), 3.68 (d, 1H, JZ
10.6 Hz, H-23a), 3.77 (ddd, 1H, JZ8.8, 5.4, 2.6 Hz, H-500),
3.94 (d, 1H,0 JZ10.8 Hz, H-23b), 4.06 (dd, 1H, JZ12.0,
1.8 Hz, H-5a ), 4.12 (dd, 1H, JZ9.2, 7.8 Hz, H-200), 4.15 (m,
1H, H-400), 4.16 (m, 1H, H-300), 4.23 (dd, 1H, JZ11.8,
4.4 Hz, H-3), 4.30 (dd, 1H, JZ010 1.7, 5.4 Hz, H-6a00), 4.39
(m, 1H, H-40), 4.44 (m, 2H, H-6b , H-5b0), 4.65 (dd, 1H, JZ
9.9, 3.3 Hz, H-30), 4.7300(dd, 1H, JZ9.9, 3.2 Hz, H-20), 5.12
(d, 1H, JZ7.5 Hz, H-1 ), 5.45 (m, 1H, H-12), 5.82 (d, 1H,
JZ3.3 Hz, H-10). 13C NMR (pyridine-d5): d 13.8 (C-24),
15.6 (C-25), 17.2 (C-26), 22.020 (C-2), 23.5 (C-30), 250.8
(C-27), 33.0 (C-29), 62.4 (C-6 ), 64.020 (C-23), 64.3 (C-5 ),
69.2 (C-30), 70.0 (C-40), 71.3 (C-4 ), 75.2 (C-200), 770.3
(C-3), 77.9 (C-300), 77.9 (C-500), 79.9 (C-20), 97.7 (C-1 ),
106.0 (C-100), 122.2 (C-12), 144.6 (C-13). HRMS:
C41H66O13Na calcd 789.4401; found 789.4374.
The saponins 1–8 were treated with excess diazomethane26
to give their corresponding methyl esters in quantitative
yields.
4.1.33. Methyl 3-O-[b-D-xylopyranosyl-(1/2)-a-L-ara-
binopyranosyl]hederagenate (1a). [a]D C39.08 (c 0.5,
pyridine). 1H NMR (CD3OD): d 0.72 (s, 3H, H-24), 0.77 (s,
3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s, 3H, H-30), 0.97–2.06
(m, 22H, H-1, H-2, H-5, H-6, H-7, H-9, H-11, H-15, H-16,
H-19, H-21, H-22), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27),
2.89 (dd, 1H,00JZ13.7, 3.9 Hz, H-18), 3.18 (dd, 1H, JZ11.1,
10.7 Hz, H-5 ), 3.23 (dd, 1H, JZ9.1, 7.7 Hz, H-200), 3.26 (d,
1H, JZ10.1 Hz, H-23), 3.33 (m, 1H, H-300), 3.48 (ddd, 1H,
JZ10.2, 8.9, 5.4 Hz, H-400), 3.54 (dd, 1H, JZ13.2, 2.6 Hz,
H-50), 3.61 (dd, 1H, JZ12.3, 4.8 Hz, H-3), 30.64 (s, 3H,
OCH3), 3.72 (m, 1H, H-23), 3.74 (m, 1H, H-3 ), 3.75 (m,
1H, H-20), 3.84 (m, 3H, H-500, H-40, H-50), 4.48 (d, 1H, JZ
6.4 Hz, H-10), 4.51 (d, 1H, JZ7.6 Hz, H-100), 5.27 (m, 1H,
H-12). 13C NMR (CD3OD): d 11.6 (C-24), 14.9 (C-25), 16.2
(C-26), 17.3 (C-6), 22.5 (C-30), 22.6 (C-16), 23.1 (C-11),
25.0 (C-27), 25.0 (C-2), 27.3 (C-15), 30.1 (C-20), 31.8
(C-7), 32.1 (C-29), 32.1 (C-22), 33.3 (C-21), 36.2 (C-10),
38.0 (C-1), 39.1 (C-8), 41.3 (C-18), 41.4 (C-14), 42.6 (C-4),
45.6 (C-19), 46.4 (C-5), 46.60 (C-17), 47.5 (C-9), 500.7
(OCH3), 62.8 (C-23), 64.7 (C-5 ), 65.7 (C-500), 68.0 (C-4 ),
69.70 (C-400), 72.6 (C-30), 74.5 (C-200), 76.4 (C-300), 79.6
(C-2 ), 81.5 (C-3), 103.3 (C-10), 104.8 (C-100), 122.3 (C-12),
143.6 (C-13), 178.6 (C-28). HRMS: C41H66O12Na calcd
773.4452; found 773.4425.
4.1.31. 3-O-[b-D-glucopyranosyl-(1/3)-a-L-arabinopyr-
anosyl]hederagenin (7). Using a stoichiometric amount of
Pd(PPh3)4 in the general deprotection method 1 described
for 5, the deprotection of saponin 36 (0.67 g, 0.43 mmol)
gave 0.27 g (78%) of 7. Use of the catalytic method with
0.060 g (0.04 mmol) of 36 gave 0.026 g (84%) of 7. [a]D
1
C46.88 (c 0.5, pyridine). Selected NMR data: H NMR
(pyridine-d5): d 0.90 (s, 6H, H-25, H-24), 0.91 (s, 3H, H-29),
0.98 (s, 3H, H-30), 0.99 (s, 3H, H-26), 1.24 (s, 3H, H-27),
3.27 (dd, 1H, JZ13.8, 4.2, H-18), 3.67 (brd, 1H, JZ12.0,
H-5a0), 3.70 (d, 1H, JZ11.0, H-23a), 4.00 (ddd, 010 H, JZ9.5,
5.3, 1.9 0Hz, H-500), 4.07 (t, 1H, JZ8.4 Hz, H-2 ), 4.15 (m,
1H, H-3 ), 4.18 (t, 1H, JZ9.1 Hz, H-400; m, 1H, H-5b0), 4.26
(m, 1H, H-3), 4.27 (t, 1H, JZ8.9 Hz, H-300), 4.32 (d, 1H, JZ
00
11.4 Hz, H-23b), 4.33 (brd, 1H, JZ11.8 Hz, H-6a ), 4.44
00
(m, 1H, H-40), 4.54 (dd, 1H, JZ11.8, 1.8 Hz, H-6b ), 4.58
(dd,0 1H, JZ9.0, 7.8 Hz, H-20), 5.01 (d, 1H, JZ7.5 Hz,
H-1 ), 5.29 (d, 1H, JZ7.8 Hz, H-100), 5.47 (m, 1H, H-12).
13C NMR (pyridine-d5): d 14.5 (C-24), 16.8 (C-25), 18.3
(C-26), 24.6 (C-30), 26.9 (C-27), 27.0 (C-2), 34.0 0(C-29),
63.200(C-600), 64.8 (C-23), 67.7 (C-50), 69.9 (C-4 ), 72.2
(C-4 ), 72.6 (C-20), 76.2 (C-200), 78.8 (C-300), 79.3 (C-500),
82.6 (C-3), 84.8 (C-30), 106.7 (C-100), 107.2 (C-100), 123.3
(C-12), 145.6 (C-13). HRMS: C41H66O13Na calcd
789.4401; found 789.4391.
4.1.34. Methyl 3-O-[b-D-xylopyranosyl-(1/2)-b-L-ara-
binopyranosyl]hederagenate (2a). [a]D C87.28 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.69
1
(s, 3H, H-24), 0.77 (s, 3H, H-26), 0.93 (s, 3H, H-30), 0.96 (s,
3H, H-29), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27), 2.89 (dd,
1H, 0J0 Z13.7, 4.1 Hz, H-18), 3.21 (dd, 1H, JZ11.3, 10.4 Hz,
H-5 ), 3.27 (dd, 1H, JZ9.0, 7.4 Hz,00H-200), 3.33 (m, 1H,
H-23), 3.34 (t, 1H, JZ8.9 Hz, H-3 ), 3.47 (d, 1H, JZ
11.2 Hz, H-23), 3.50 (m, 1H, H-400), 3.59 (dd, 1H, JZ12.4,
1.2 Hz, H-50), 3.64 (s, 3H, OCH3), 3.65 (dd, 1H, JZ11.4,
4.7 Hz, H-3), 3.83 (dd, 1H, JZ9.3, 3.4 Hz, H-200), 3.88 (dd,
1H, JZ11.4, 5.3 Hz, H-500), 3.94 (m, 1H, H-4 ), 3.95 (m,
1H, H-30), 3.9800(brd, 1H, JZ12.2 Hz, H-50), 4.41 (d, 1H,
JZ7.4 Hz, H-1 ), 5.14 (d, 1H, JZ3.4 Hz, H-10), 5.28 (m,
1H, H-12). 13C NMR (CD3OD): d 12.4 (C-24), 14.8 (C-25),
4.1.32. 3-O-[b-D-glucopyranosyl-(1/4)-a-L-arabinopyr-
anosyl]hederagenin (8). Using a stoichiometric amount of
Pd(PPh3)4 in the general deprotection method 1 described
for 5, the deprotection of saponin 37 (0.80 g, 0.50 mmol)
gave 0.34 g (82%) of 8. Use of the catalytic method with
0.122 g (0.08 mmol) of 37 gave 0.041 g (65%) of 8. [a]D
1
C35.58 (c 0.53, CH3OH). Selected NMR data: H NMR
(pyridine-d5): d 0.89 (s, 3H, H-24), 0.91 (s, 3H, H-29), 0.91

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16.2 (C-26), 21.6 (C-2), 22.5 0 (C-30), 25.0 (C-27), 32.1
(C-29), 50.7 (OCH3), 63.2 (C-5 ), 63.5 (C-23), 65.4 (C-500),
68.100(C-30), 69.4 (C-40), 69.07 (C-400), 73.9 (C-200), 76.3
(C-3 ), 77.2 (C-3), 78.4 (C-2 ), 97.0 (C-10), 105.4 (C-100),
122.3 (C-12), 143.6 (C-13), 178.6 (C-28). HRMS:
C41H66O12Na calcd 773.4452; found 773.4456.
(C-26), 22.5 (C-30), 24.9 (C-2), 25.0 (C-27), 32.0 (C-29),
50.7 (OCH3), 61.4 (C-600), 63.3 (C-23), 64.1 (C-50), 67.6
(C-40), 70.2 (C-400), 72.4 (C-30), 74.5 (C-200), 76.5 (C-300),
76.800(C-500), 77.9 (C-20), 82.2 (C-3), 103.1 (C-10), 103.2
(C-1 ), 122.3 (C-12), 143.6 (C-13), 178.6 (C-28). HRMS:
C42H68O13Na calcd 803.4558; found 803.4554.
4.1.35. Methyl 3-O-[b-D-xylopyranosyl-(1/3)-a-L-ara-
binopyranosyl]hederagenate (3a). [a]D C49.08 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.74
4.1.38. Methyl 3-O-[b-D-glucopyranosyl-(1/2)-b-L-ara-
binopyranosyl]hederagenate (6a). [a]D C72.28 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.69
1
1
(s, 3H, H-24), 0.77 (s, 3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27), 2.89 (dd,
1H, 0J0 Z13.5, 3.4 Hz, H-18), 3.23 (dd, 1H, JZ11.0, 10.7 Hz,
H-5 ), 3.31 (m,010 H, H-23), 3.32 (m, 1H, H-200), 3.36 (t, 1H,
JZ8.2 Hz, H-3 ), 3.52 (m, 1H, H-4000), 3.58 (brd, 1H, JZ
12.4 Hz, H-50), 3.63 (m, 2H, H-3, H-3 ), 3.64 (s, 3H, OCH3),
3.65 (m, 1H, H-23), 3.71 (dd, 1H, JZ9.3, 7.6 Hz, H-20),
3.87 (dd, 1H, JZ12.4, 2.0 Hz, H-50), 3.88 (dd, 1H, JZ11.3,
5.4 Hz, H-500), 3.97 (m, 1H, H-40), 4.36 (d, 1H, JZ7.5 Hz,
H-10), 4.53 (d, 1H, JZ7.1 Hz, H-100), 5.27 (m, 1H, H-12).
13C NMR (CD3OD): d 11.9 (C-24), 15.0 (C-25), 16.2
(C-26), 22.5 (C-30), 25.1 (C-27), 32.1 (C-29), 50.8 (OCH3),
63.600(C-23), 65.4 (C-50), 65.5 (C-500), 68.3 (C-40), 69.6
(C-4 ), 70.7 (C-20), 73.7 (C-200), 76.0 (C-300), 82.0 (C-3),
82.2 (C-30), 104.7 (C-10, C-100), 122.3 (C-12), 143.6 (C-13),
178.5 (C-28). HRMS: C41H66O12Na calcd 773.4452; found
773.4450.
(s, 3H, H-24), 0.77 (s, 3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27), 2.90 (dd,
1H, JZ13.8, 3.9 Hz, H-18), 3.27 (m, 1H, H-400), 3.28 (m,
1H, H-200), 3.30 (m, 1H, H-500), 3.34 (m, 1H, H-23a), 3.38 (t,
1H, JZ8.8 Hz, H-300), 3.50 (d, 1H, JZ11.1 Hz, H-23b),
3.60 (dd, 1H, JZ12.1, 1.6 Hz, H-5a0), 3.64 (s, 3H, OCH3),
3.67 (dd, 1H, JZ11.8, 5.7 Hz, H-6a00), 3.72 (dd, 1H, JZ
11.6, 4.5 Hz, H-3), 3.86 (dd, 1H0,0 JZ9.5, 3.3 Hz, H-200), 3.90
(dd, 1H, JZ11.8, 2.0 Hz, H-6b ), 3.94 (m, 1H, H-4 ), 3.96
(dd, 1H, JZ9.7, 3.4 Hz, H-30), 3.99 (brd, 1H, JZ12.0 Hz,
H-5b0), 4.49 (d, 1H, JZ7.7 Hz, H-100), 5.28 (m, 1H, H-12; d,
1H, JZ3.2 Hz, H-10). 13C NMR (CD3OD): d 12.4 (C-24),
14.8 (C-25), 16.2 (C-26), 22.1 (C-2), 22.5 (C-30), 250.0
(C-27), 32.0 (C-29), 50.7 (OCH3), 61.5 (C-600), 63.3 (C-5 ),
63.500(C-23), 68.0 (C-30), 69.4 (C-40), 70.3 (C-400), 740.2
(C-2 ), 76.5 (C-300), 76.6 (C-500), 78.0 (C-3), 78.6 (C-2 ),
97.8 (C-10), 104.5 (C-100), 122.4 (C-12), 143.6 (C-13), 178.6
(C-28). HRMS: C42H68O13Na calcd 803.4558; found
803.4554.
4.1.36. Methyl 3-O-[b-D-xylopyranosyl-(1/4)-a-L-ara-
binopyranosyl]hederagenate (4a). [a]D C45.28 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.69
1
4.1.39. Methyl 3-O-[b-D-glucopyranosyl-(1/3)-a-L-ara-
binopyranosyl]hederagenate (7a). [a]D C47.08 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.84
(s, 3H, H-24), 0.73 (s, 3H, H-26), 0.89 (s, 3H, H-29), 0.92 (s,
3H, H-30), 0.96 (s, 3H, H-25), 1.15 (s, 3H, H-27), 2.85 (dd,
1H, 0J0 Z13.7, 3.8 Hz, H-18), 3.16 (dd, 1H, JZ11.0, 10.8 Hz,
H-5 ), 3.25 (m, 1H, H-200), 3.26 (d, 1H, JZ11.4 Hz, H-23),
3.29 (m, 1H, H-300), 3.46 (m, 1H, H-400), 3.50 (m, 1H, H-20),
3.51 (m, 1H, H-50), 3.53 (m, 1H, H-30), 3.58 (dd, 1H, JZ
11.5, 4.7 Hz, H-3), 3.59 (m, 1H, H-23), 3.60 (s, 3H, OCH3),
3.85 (dd, 1H, JZ11.4, 5.3 Hz, H-500), 3.83 (m, 1H, H-40),
4.03 (dd, 10H, JZ12.6, 2.4 Hz, H-50), 4.28 (d, 1H, JZ
6.4 Hz, H-1 ), 4.39 (d, 1H, JZ7.1 Hz, H-100), 5.23 (m, 1H,
H-12). 13C NMR (CD3OD): d 11.9 (C-24), 14.9 (C-25), 16.2
(C-26), 22.5 (C-30), 25.0 (C-27), 32.1 (C-29), 50.7 (OCH3),
63.30 (C-23), 65.1 (C-50), 65.5 (C-500), 69.6 (C-400), 710.9
(C-2 ), 73.0 (C-30), 73.8 (C-200), 760.03 (C-300), 78.4 (C-4 ),
82.0 (C-3), 104.9 (C-10), 105.6 (C-1 ), 122.3 (C-12), 143.6
(C-13), 178.6 (C-28). HRMS: C41H66O12Na calcd
773.4452; found 773.4441.
1
(s, 3H, H-24), 0.87 (s, 3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27), 2.89 (dd,
1H, JZ13.5, 4.0 Hz, H-18), 3.30 (m, 1H, H-500), 3.32 (m,
1H, 00H-200), 3.32 (m, 1H, H-23a),00 3.37 (t, 1H, JZ8.5 Hz,
H-4 ), 3.40 (t, 1H, JZ8.6 Hz, H-3 ), 3.59 (dd, 1H, JZ12.8,
1.2 Hz, H-5a0), 3.64 (s, 3H, OCH3; m, 1H, H-3), 3.65 (m,
1H, H-30; d, 1H, JZ11.6 Hz, H-23b), 3.71 (dd, 1H, JZ12.1,
5.4 Hz, H-6a00; dd, 1H, 0J0 Z9.8, 7.5 Hz, H-20), 3.85 (dd, 1H,
JZ11.9, 2.1 Hz, H-6b ),0 3.88 (dd, 1H, JZ13.0, 2.2 Hz,
H-5b0), 4.06 (m, 1H, H-4 ), 4.37 (d, 1H, JZ7.4 Hz, H-10),
4.56 (d, 1H, JZ7.7 Hz, H-100), 5.27 (brt, 1H, JZ3.3 Hz,
H-12). 13C NMR (CD3OD): d 11.9, (C-24), 15.0 (C-25),
16.2 (C-26), 22.5 (C-30), 24.8 (C-2), 25.0 (C-27), 320.0
(C-29), 50.7 (OCH3), 60.9 (C-600), 63.7 (C-23), 65.4 (C-5 ),
68.100(C-40), 69.700 (C-400), 70.6 (C-20), 73.9 (C-200), 76.2
(C-3 ), 76.5 (C-5 ), 82.0 (C-3), 82.8 (C-30), 104.1 (C-100),
104.7 (C-10), 122.3 (C-12), 143.6 (C-13), 178.6 (C-28).
HRMS: C42H68O13Na calcd 803.4558; found 803.4534.
4.1.37. Methyl 3-O-[b-D-glucopyranosyl-(1/2)-a-L-ara-
binopyranosyl]hederagenate (5a). [a]D C39.88 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.74
1
(s, 3H, H-24), 0.77 (s, 3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-27), 2.89 (dd,
1H, 00JZ13.6, 3.9 Hz, H-18), 3.23 (dd, 1H, JZ8.7, 7.9 Hz,
4.1.40. Methyl 3-O-[b-D-glucopyranosyl-(1/4)-a-L-ara-
binopyranosyl]hederagenate (8a). [a]D C22.18 (c 0.5,
pyridine). Selected NMR data: H NMR (CD3OD): d 0.73
1
00
H-2 ), 3.25 (t, 1H, JZ9.1 Hz, H-400), 3.28 (m, 1H, H-5 ),
(s, 3H, H-24), 0.77 (s, 3H, H-26), 0.93 (s, 3H, H-29), 0.96 (s,
3H, H-30), 1.00 (s, 3H, H-25), 1.19 (s, 3H, H-020 7), 2.89 (dd,
1H, JZ13.7, 3.9 Hz, H-18), 3.30 (m, 2H, H-2 , H-500), 3.32
(m, 1H, H-23a), 3.33 (m,01H, H-400), 3.37 (t, 1H, JZ8.6 Hz,
H-300), 3.56 (m, 3H, H-2 , H-30, H-5a0), 3.63 (m, 1H, H-3),
3.64 (s, 3H, OCH3; d, 1H, JZ11.2 Hz, H-23b), 3.68 (dd,
1H, J0Z0 12.0, 5.3 Hz, H-6a00), 3.87 (dd, 1H, JZ12.1, 2.1 Hz,
H-6b ), 3.93 (m, 1H, H-40), 4.20 (dd, 1H, JZ12.7, 2.4 Hz,
00
3.32 (m, 1H, H-23a), 3.38 (dd, 1H0, JZ9.0, 8.7 Hz, H-3 ),
3.54 (dd, 1H, JZ13.3, 3.3 Hz, H-5a ), 3.64 (s, 3H, OCH3; m,
1H, H-3), 3.65 (m, 1H, H-6a00), 3.67 (d, 1H, JZ11.2 Hz,
H-23b), 3.77 (dd, 1H, JZ8.1, 3.1 Hz, H-30), 3.85 (m, 1H,
H-40), 3.86 (m, 3H, H-6b00, H-5b0, H-20), 4.56 (d, 1H, JZ
6.2 Hz, H-10), 4.63 (d, 1H, JZ7.8 Hz, H-100), 5.27 (m, 1H,
H-12). 13C NMR (CD3OD): d 11.9 (C-24), 14.9 (C-25), 16.2

´
K. Ple et al. / Tetrahedron 61 (2005) 4347–4362
4362
H-5b0), 4.33 (d, 1H, JZ6.8 Hz, H-10), 4.49 (d, 1H, JZ
7.6 Hz, H-100), 5.27 (m, 1H, H-12). 13C NMR (CD3OD): d
11.9 (C-24), 14.9 (C-25), 16.2 (C-26), 22.5 (C-30), 24.7
(C-2), 25.0 (C-27), 32.1 (C-29), 50.7 (OCH3), 61.1 (C-600),
63.30 (C-23), 65.1 (C-50), 69.8 (C-400), 71.9 (C-20), 730.0
(C-3 ), 73.9 (C-200), 76.4 (C-300), 76.5 (C-500), 78.5 (C-4 ),
81.9 (C-3), 104.8 (C-10), 104.9 (C-100), 122.3 (C-12), 143.6
(C-13), 178.6 (C-28). HRMS: C42H68O13Na calcd
803.4558; found 803.4531.
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Acknowledgements
The authors would like to thank the CNRS (Centre National
de Recherche Scientifique) and the French Research
Ministry for financial support as well as the PhD scholarship
for MC.
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