Synthesis of a typical glucuronide-containing saponin, 28-O-β-D- glucopyranosyl oleanate 3-O-β-D-galactopyranosyl-(1→2)-[β-D- glucopyranosyl-(1→3)]-β-D-glucuronopyranoside

Article abstract of DOI:10.1055/s-2004-829103

28-O-β-D-Glucopyranosyl oleanate 3-O-β-D-galactopyranosyl- (1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-glucuronopyranoside (1), a structurally typical glucuronide-containing triterpene saponin isolated from Aralia dasyphylla, was concisely synthesized in linear nine steps and 26% overall yield. The key features of the synthesis are: (1) attachment of the 28-glucosyl ester ahead of assembly of the 3-O-sugar chain; (2) elaboration of the glucuronide residue at a later stage via the TEMPO-mediated selective oxidation; (3) installation of 2-(azidomethyl)benzoyl group as a benzoylic neighboring participating group which is selectively removed afterwards for synthesis of the 1→2 sugar linkage.

Full text of DOI:10.1055/s-2004-829103

PAPER
1641
Synthesis of a Typical Glucuronide-Containing Saponin,
28-O-b-D-Glucopyranosyl Oleanate 3-O-b-D-Galactopyranosyl-(1→2)-
[b-D-glucopyranosyl-(1→3)]-b-D-glucuronopyranoside
Synthesis of
a
Typical
G
e
lucuronide
n
-Containing
j
Saponi
i
e Peng,a Xiuwen Han,a Biao Yu*b
a
State Key Laboratory of Catalyst, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, P. R. of China
b
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, P. R. of China
E-mail: byu@mail.sioc.ac.cn
Received 27 February 2004; revised 25 March 2004
Abstract: 28-O-b-D-Glucopyranosyl oleanate 3-O-b-D-galactopyr-
anosyl-(1→2)-[b-D-glucopyranosyl-(1→3)]-b-D-glucuronopyrano-
side (1), a structurally typical glucuronide-containing triterpene
saponin isolated from Aralia dasyphylla, was concisely synthesized
in linear nine steps and 26% overall yield. The key features of the
synthesis are: (1) attachment of the 28-glucosyl ester ahead of as-
sembly of the 3-O-sugar chain; (2) elaboration of the glucuronide
residue at a later stage via the TEMPO-mediated selective oxida-
tion; (3) installation of 2-(azidomethyl)benzoyl group as a benzoyl-
ic neighboring participating group which is selectively removed
afterwards for synthesis of the 1→2 sugar linkage.
Figure 1
Keywords: triterpene saponin, glucuronide, synthesis, glycosyla-
tion, oxidation
the four glucose and galactose residues determines the
synthetic route toward saponin 1. Highly selective glyco-
sylation of the 28-COOH of an oleanolic triterpene with a
glycosyl bromide, in the presence of the 3-OH, has been
demonstrated.6 A convergent manner would therefore call
for the subsequent assembly of the remaining 3-OH with
a trisaccharide donor. However, the 3-O-trisaccharide
bearing a 1→2 linkage, which is a common pattern in tri-
terpene saponins,3 precludes the use of a trisaccharide do-
nor with a neighboring participating group to ensure a
stereospecific glycosylation. We thus planned to assemble
a Glu-(1→3)-Glu donor installed with a participating
group at the 2-OH, and then follow with a selective re-
moval of the 2-O-group and a subsequent glycosylation
with a galactosyl donor (e.g., 5). For construction of the
1,2-trans-glycosidic bond at the 3-OH of triterpenoids and
steroids, the glycosylation conditions have been opti-
mized,7 where glycosyl trichloroacetimidate (or trifluoro-
acetimidate)8 donors with a benzoyl group at 2-OH and
TMSOTf as catalyst are required. Thus, disaccharide tri-
fluoroacetimidate donor 4 was designed: the 2-(azido-
methyl)benzoyl (AZMB) group, a benzoylic group
capable of selective removal under reductive conditions,9
was chosen as the 2-O-group; the 4,6-O-acetyl groups
were expected to be removed in the presence of benzyl
groups at a later stage for introduction the 6¢-carboxylic
function.10 Benzoyl group was selected as the permanent
protecting group, which could be taken off under alkaline
conditions without affecting the robust 28-glycosyl ester
linkage.11
28-O-b-D-Glucopyranosyl oleanate 3-O-b-D-galactopyra-
nosyl-(1→2)-[b-D-glucopyranosyl-(1→3)]-b-D-glucuro-
nopyranoside (1) was isolated from Aralia dasyphylla
Miq. (Araliaceae), a Chinese folk medicinal plant used for
treatment of hepatitis and diabetes.1 This compound was
claimed to be highly cytotoxic, with IC50 values of 1.2 mg/
mL and 0.02 mg/mL against two cultured human cancer
cell lines, KB and Hela-S3 cells, respectively.1 In fact, an
early report has mentioned the same structure being isolat-
ed from Polyscias fruticosa (L.) Harms. (Araliaceae).2
However, two reports provided quite different 1H and 13C
NMR data as well as the optical rotation value for this
compound.1,2 Structurally, saponin 1 represents a typical
member of the family termed glucuronide oleanane-type
triterpene carboxylic acid 3,28-O-bisdesmoside (GOT-
CAB).3 We have recently reported the first synthesis of a
GOTCAB saponin, ginsenoside Ro [28-O-b-D-glucopyr-
anosyl oleanate 3-O-b-D-glucopyranosyl-(1→2)-b-D-glu-
curonopyranoside].4 Here we report a full account on the
synthesis of saponin 1 (Figure 1).
Adopting the common tactic for introduction of uronate
residues in the synthesis of complex oligosaccharides and
glycoconjugates,5 we scheduled to elaborate the 6¢-car-
boxyl function via a selective oxidation of the primary 6¢-
OH of 2 (Scheme 1) at a later stage after assembly of the
tetrasaccharide. Therefore, the sequence for assembly of
Disaccharide trifluoroacetimidate 4 was readily prepared
as shown in Scheme 2. Regioselective glycosylation of
the 2,3-diol 6 (allyl 4,6-O-benzylidene-a-D-glucopyrano-
side) with 2,3,4,6-tetra-O-benzoyl-D-glucopyranosyl
SYNTHESIS 2004, No. 10, pp 1641–1647
Advanced online publication: 16.06.2004
DOI: 10.1055/s-2004-829103; Art ID: F03104SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4

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W. Peng et al.
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Scheme 2 Preparation of the disaccharide donor 4: Reagents and
conditions: (a) 8 (1.0 equiv), TMSOTf (0.06 equiv), CH2Cl2, 4 Å MS,
0 °C–r.t., 92% (for a mixture of the 2-O- and 3-O-glycosylated iso-
mers). (b) AZMBCl, DMAP, CH2Cl2, r.t., 66% (for 9, 2 steps). (c)
AZMBCl, pyridine–CH2Cl2, 0 °C, 78%. (d) 8 (2.0 equiv), TMSOTf
(0.1 equiv), CH2Cl2, 4 Å MS, r.t., 62%. (e) p-TsOH, MeOH–CH2Cl2,
reflux, 97%. (f) Ac2O, pyridine–CH2Cl2, r.t., 98%. (g) PdCl2 (0.7
equiv), MeOH–CH2Cl2, r.t., 84%. (h) PhN=CClCF3, K2CO3, acetone,
r.t., 91%.
Scheme 1 Retrosynthetic plan
trichloroacetimidate to give the 1→3 linked disaccharide
has been reported.12 However, under similar reaction con-
ditions (0.06 equiv of TMSOTf, CH2Cl2, 4 Å MS, 0 °C–
r.t.), coupling of 6 with 8 (or its trichloroacetimidate coun-
terpart) gave a mixture of the 2-O- and 3-O-glycosylated
isomers, which are inseparable on silica gel. Subsequent in 90% yield (Scheme 3). The anomeric proton appeared
acylation with AZMBCl provided the corresponding re- at d = 5.96 ppm (d, J = 8.1 Hz). Next, glycosylation of 13
gioisomers in a ratio of 3.5:1 in favor of the desired 3-O- with 4 in the presence of a catalytic amount of TMSOTf
glycosylated isomer 9 (66% yield for two steps). Alterna- (0.1 equiv) afforded the desired b-bismoside 14 (H-1¢,
tively, regioselective benzoylation (and pivaloylation) of 4.44 ppm, d, J = 7.4 Hz) in high yield (89%). Selective re-
the 2-OH of 6 is feasible.13 Treatment of 6 with AZMBCl moval of the 2¢-O-AZMB group with PBu3 in the presence
in pyridine–CH2Cl2 at 0 °C provided the 2-O-AZMB of acetyl and benzoyl groups was achieved,9 providing 15
product 7 [d = 5.03 (dd, J = 9.6, 3.6 Hz, H-2)] in a satis- in 90% yield. Subsequent glycosylation of the resulting
factory yield (78%) with an easy purification. And the 2¢-OH of 15 with galactosyl trifluoroacetimidate 5 in the
2,3-di-O-AZMB product [d = 5.33 (overlapped H-2), d = presence of TBSOTf (0.4 equiv) afforded the b-glycosyl-
6.09 (t, J = 9.9 Hz, H-3)] was isolated in 6% yield. Gly- ated tetrasaccharide 16 in an excellent yield (90%). Here,
cosylation of the hindered 3-OH of 7 with trifluoroacetim- the use of TBSOTf as the catalysis in place of TMSOTf
idate 8 in the presence of a catalytic amount of TMSOTf improved the glycosylation yield by avoiding the produc-
(0.1 equiv) afforded the desired disaccharide 9 in a com- tion of the corresponding 2¢-O-TMS ether. Selective re-
promised 62% yield. In comparison, coupling of 7 with moval of the 4¢,6¢-O-acetate on 16 with 1% HCl in MeOH
2,3,4,6-tetra-O-benzoyl-D-glucopyranosyl trichloroace- in the presence of 12 benzoyl groups met with no prob-
timidate under similar conditions was examined, provid- lem, providing 4¢,6¢-diol 2 in 88% yield.10 Diol 2 was then
ing 9 in 52% yield. To avoid problems associated with subjected to selective oxidation with a modified oxidation
cleavage of the anomeric allyl group,14 the 4,6-ben- protocol of TEMPO/KBr/Ca(ClO)2 under phase-transfer
zylidene 9 was converted to the 4,6-di-O-acetate 11. aqueous conditions.16 In order to facilitate purification
Treatment of 11 with PdCl2 in MeOH–CH2Cl2 at room and characterization, the resulting 6¢-carboxylic acid de-
temperature provided the corresponding hemiacetal 12 in rivative was directly subjected to methylation with CH2N2
84% yield,15 which was directly subjected to addition with to provide methyl ester 17 in 72% isolated yield. Finally,
N-phenyl-2,2,2-trifluoroacetimidoyl chloride (K2CO3, ac- removal of the benzoyl groups with NaOMe in MeOH–
etone, r.t.),8 affording the desired trifluoroacetimidate 4 in CH2Cl2 gave the methyl ester of saponin 1 (18) in 85%
91% yield.
yield. Further treatment of 18 with aq NaOH (0.5 N) af-
forded the target saponin 1 (78%). All the analytical data
of 1 are in full agreement with those reported for the sapo-
nin isolated from Aralia dasyphylla.1
Expectedly, treatment of oleanolic acid with 2,3,4,6-tetra-
O-benzoyl-a-D-glucopyranosyl bromide (3) under the
slightly modified literature conditions (K2CO3, Bu4NBr,
CH2Cl2–H2O, reflux)6 provided the 28-glucosyl ester 13
Synthesis 2004, No. 10, 1641–1647 © Thieme Stuttgart · New York

PAPER
Synthesis of a Typical Glucuronide-Containing Saponin
1643
or a VG Quatro mass spectrometer. Elemental analyses were per-
formed on a Perkin Elmer Model 2400 instrument.
Allyl 2-O-(2-azidomethyl)benzoyl-4,6-O-benzylidene-a-D-glu-
copyranoside (7)
To a stirred solution of compound 6 (450 mg, 1.46 mmol) in anhyd
CH2Cl2 (4 mL) at 0 °C under Ar was added anhyd pyridine (2 mL),
followed by a solution of AZMBCl (2.0 equiv) in CH2Cl2. After be-
ing stirred at 0 °C for 2 h, the reaction was quenched with water and
diluted with CH2Cl2. The organic phase, after being washed with aq
2 N HCl and brine, was dried over Na2SO4, and then concentrated
in vacuo. The residue was applied to a silica gel column chromatog-
raphy (petroleum ether–EtOAc, 5:1) to give 7 as a yellow syrup
(529 mg, 78%); [a]D +68.6 (c = 1.17, CHCl3).
IR (film): 3459, 2870, 2104, 1720, 1602, 1580, 1453, 1379, 1333,
1263, 1144, 1120, 1085, 1035, 995, 927, 752, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.10 (d, J = 7.5 Hz, 1 H), 7.60–
7.37 (m, 8 H), 5.85 (m, 1 H), 5.60 (s, 1 H), 5.28 (dd, J = 10.5, 1.5
Hz, 1 H), 5.26 (d, J = 3.9 Hz, 1 H), 5.18 (dd, J = 10.5, 1.5 Hz, 1 H),
5.03 (dd, J = 9.6, 3.6 Hz, 1 H), 4.89 (d, J = 13.5 Hz, 1 H), 4.66 (d,
J = 14.1 Hz, 1 H), 4.40 (t, J = 9.5 Hz, 1 H), 4.32 (dd, J = 5.4, 4.8 Hz,
1 H), 4.22 (dt, J = 15.0, 3.9 Hz, 1 H), 4.06–3.93 (m, 2 H), 3.80 (t,
J = 10.4 Hz, 1 H), 3.68 (t, J = 9.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 166.2, 136.9, 133.3, 133.0, 131.8,
131.6, 130.0, 129.5, 129.2, 128.5, 128.2, 127.9, 126.2, 117.7, 101.9,
95.7, 81.2, 74.5, 68.7, 68.6, 68.5, 62.3, 53.2.
ESI–MS: m/z = 490.1 [M + Na+].
Anal. Calcd for C24H25N3O7: C, 61.66; H, 5.39; N, 8.99. Found: C,
61.35; H, 5.41; N, 9.68.
Allyl 2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-2-O-
(2-azidomethyl)benzoyl-4,6-O-benzylidene-a-D-glucopyrano-
side (9)
To a mixture of 7 (86 mg, 0.18 mmol), 8 (282 mg, 0.37 mmol), and
4 Å molecular sieves in anhyd CH2Cl2 (2 mL) was added TMSOTf
in CH2Cl2 (0.10 equiv) under Ar at r.t. After being stirred for 3 h,
the mixture was neutralized with Et3N, and then filtered and con-
centrated. The residue was purified by a flash column chromatogra-
phy on silica gel (petroleum ether–EtOAc, 3:1) to give 9 (118 mg,
62%) as a white foam; [a]D +56.8 (c = 0.97, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.95 (d, J = 8.4 Hz, 2 H), 7.89 (d,
J = 7.5 Hz, 1 H), 7.82 (d, J = 8.7 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H),
7.59–7.25 (m, 18 H), 7.20 (t, J = 6.6 Hz, 2 H), 7.06 (t, J = 7.5 Hz, 2
H), 5.78 (t, J = 9.9 Hz, 1 H), 5.75 (m, 1 H), 5.65 (s, 1 H), 5.64 (t,
Scheme 3 Synthesis of saponin 1: Reagents and conditions: (a)
K2CO3, Bu4NBr, CH2Cl2–H2O, reflux, 90%. (b) TMSOTf (0.1 equiv),
CH2Cl2, 4 Å MS, r.t., 89%. (c) Bu3P, THF–H2O, r.t., 90%. (d)
TBSOTf (0.4 equiv), CH2Cl2, 4 Å MS, r.t., 90%. (e) 1% AcCl,
MeOH–CH2Cl2, 0 °C–r.t., 88%. (f) TEMPO, Ca(ClO)2, KBr,
Bu4NBr, CHCl3–H2O, 0 °C; then CH2N2, Et2O, 0 °C, 72%. (g)
NaOMe, MeOH–CH2Cl2, r.t., 85%. (h) aq. NaOH (0.5 N), MeOH–
CH2Cl2, r.t., 78%.
In summary, 28-O-b-D-glucopyranosyl oleanate 3-O-b-D-
galactopyranosyl-(1→2)-[b-D-glucopyranosyl-(1→3)]-b-
D-glucuronopyranoside (1), a structurally typical glucu- J = 9.6 Hz, 1 H), 5.49 (t, J = 8.1 Hz, 1 H), 5.20 (dt, J = 17.4, 1.2 Hz,
1 H), 5.16–5.08 (m, 4 H), 4.68 (d, J = 15 Hz, 1 H), 4.52–4.41 (m, 2
ronide-containing triterpene saponin isolated from Aralia
dasyphylla, was concisely synthesized in linear nine steps
and 26% overall yield. The key features of the synthesis
are: (1) attachment of the 28-glucosyl ester before assem-
bly of the 3-O-sugar chain; (2) elaboration of the glucu-
ronide residue at a later stage via the TEMPO-mediated
H), 4.35–4.22 (m, 3 H), 4.14 (m, 1 H), 4.02–3.91 (m, 3 H), 3.86 (t,
J = 9.3 Hz, 1 H), 3.82 (t, J = 9.3 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 166.1, 165.7, 165.2, 165.0, 164.8,
138.0, 137.1, 133.3, 133.1, 133.0, 132.7, 131.1, 129.7, 129.6, 129.3,
129.2, 129.1, 128.8, 128.7, 128.3, 128.2, 128.0, 127.4, 126.0, 118.0,
101.5, 101.0, 95.6, 79.8, 76.4, 73.1, 73.0, 72.2, 71.9, 69.7, 68.8,
selective oxidation; (3) installation of AZMB as a ben-
63.1, 62.6, 52.7.
zoylic neighboring participating group in a glycosyl donor
ESI–MS: m/z = 1068.3 [M + Na+].
and removal of AZMB selectively afterwards for assem-
bly of the 1→2 sugar linkage.
Anal. Calcd for C58H51N3O16·H2O: C, 65.51; H, 5.02; N, 3.97.
Found: C, 65.89; H, 4.87; N, 3.96.
Allyl 2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-2-O-
(2-azidomethyl)benzoyl-a-D-glucopyranoside (10)
A solution of compound 9 (1.40 g, 1.3 mmol) and p-TsOH (254 mg,
1.3 mmol) in MeOH–CH2Cl2 (10 mL:10 mL) was refluxed for 5 h.
The mixture was then neutralized with Et3N and concentrated. The
residue was purified by a flash column chromatography on silica gel
Solvents were purified in the usual way. TLCs were performed on
precoated plates of silica gel HF254 (0.5 mm, Yantai, China). Flash
column chromatography was performed on silica gel H (10–40 mM,
Yantai, China). Optical rotations were determined with a Perkin
Elmer Model 241 MC polarimeter. NMR spectra were recorded on
a Bruker AM 300 spectrometer with Me4Si as the internal standard.
J values are given in Hz. Mass spectra were obtained on a HP5989A
Synthesis 2004, No. 10, 1641–1647 © Thieme Stuttgart · New York

1644
W. Peng et al.
PAPER
(3:2 petroleum ether–EtOAc) to yield 10 (1.24 g, 97%) as a white
foam; [a]D +45.2 (c = 1.05, CHCl3).
13C NMR (75 MHz,CDCl3): d = 166.1, 165.7, 135.1, 164.9, 164.8,
138.3, 133.4, 133.3, 132.8, 131.2, 129.7, 129.6, 129.5, 129.3, 128.8,
128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.0, 101.5, 89.8, 76.3,
73.8, 72.9, 72.0, 69.5, 67.9, 67.5, 63.1, 62.2, 52.8, 20.7, 20.5.
1H NMR (300 MHz, CDCl3): d = 8.15 (d, J = 8.7 Hz, 2 H), 7.90 (d,
J = 8.4 Hz, 2 H), 7.85 (d, J = 7.5 Hz, 1 H), 7.72 (d, J = 8.4 Hz, 2 H),
7.61–7.18 (m, 15 H), 6.94 (t, J = 7.8 Hz, 2 H), 5.88 (t, J = 9.9 Hz, 1
H), 5.70 (m, 1 H), 5.62 (t, J = 10.0 Hz, 1 H), 5.52 (t, J = 8.9 Hz, 1
H), 5.18 (d, J = 17.1 Hz, 1 H), 5.06 (m, 3 H), 4.95 (dd, J = 9.3, 3.9
Hz, 1 H), 4.81 (d, J = 11.7 Hz, 1 H), 4.65 (d, J = 15.3 Hz, 1 H), 4.41
(dd, J = 11.7, 6.6 Hz, 1 H), 4.28 (m, 1 H), 4.19–4.02 (m, 3 H), 3.98–
3.85 (m, 3 H), 3.84–3.70 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 166.1, 165.6, 165.1, 164.9, 164.7,
138.0, 133.6, 133.3, 133.2, 132.9, 132.7, 131.1, 129.9, 129.8, 129.5,
129.1, 129.0, 128.4, 128.3, 128.2, 127.9, 126.8, 117.8, 101.7, 94.7,
82.5, 72.7, 72.4, 72.2, 71.6, 71.1, 69.36, 69.2, 68.4, 62.6, 52.7.
+
ESI-MS: m/z = 1019.1 [M + NH4 ].
Anal. Calcd for C52H47N3O18·1/2H2O: C, 61.78; H, 4.79; N, 4.17.
Found: C, 61.63; H, 4.75; N, 4.01.
2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-4,6-di-O-
acetyl-2-O-(2-azidomethyl)benzoyl-a/b-D-glucopyranosyl
N-(Phenyl)trifluoroacetimidate (4)
To a stirred mixture of 12 (1.05g, 1.04 mmol) and K2CO3 (468 mg,
3.0 equiv) in acetone (20 mL) under Ar at r.t. was added N-(phe-
nyl)trifluoroacetimidoyl chloride (185 L, 1.2 equiv). After being
stirred at r.t. for 7 h, the mixture was filtered and concentrated. The
residue was purified by a flash column chromatography on silica gel
(petroleum ether–EtOAc, 5:2) to afford 4 (a and b mixture, 1.11 g,
91%) as a white solid.
+
ESI–MS: m/z = 975.4 [M + NH4 ].
Anal. Calcd for C51H47N3O16·H2O: C, 62.77; H, 5.06; N, 4.32.
Found: C, 63.15; H, 4.28; N, 3.94.
Allyl 2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-4,6-
di-O-acetyl-2-O-(2-azidomethyl)benzoyl-a-D-glucopyranoside
(11)
To a solution of compound 10 (1.09 g, 1.14 mmol) in anhyd pyri-
dine (10 mL) at 0 °C was added acetic anhydride (1.15 mL, 11.4
mmol) dropwise. The mixture was stirred at r.t. for 2 h. After a con-
ventional workup, the residue was subjected to a column chroma-
tography on silica gel (petroleum ether–EtOAc, 2:1) to yield 11
(1.17 g, 98%) as a white solid; [a]D +33.3 (c = 0.70, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.08 (m, 3 H), 7.87 (d, J = 8.4 Hz,
2 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.76–7.19 (m, 15 H), 7.04 (t, J = 7.0
Hz, 2 H), 5.84–5.63 (m, 3 H), 5.46 (t, J = 8.4 Hz, 1 H), 5.20 (d, J =
17.1 Hz, 1 H), 5.18–5.07 (m, 4 H), 4.95 (dd, J = 9.9, 2.9 Hz, 1 H),
4.68 (m, 2 H), 4.50 (dd, J = 12.1, 4.6 Hz, 1 H), 4.38 (t, J = 10.0 Hz,
1 H), 4.24–4.15 (m, 2 H), 4.14–4.05 (m, 3 H), 3.98–3.89 (m, 2 H),
2.10 (s, 3 H), 1.97 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 170.7, 169.3, 166.1, 165.7, 165.1,
164.9, 164.8, 138.4, 133.4, 133.3, 133.0, 132.8, 131.1, 129.8, 129.7,
129.6, 129.5, 129.3, 128.8, 128.7, 128.6, 128.4, 128.2, 128.0, 127.0,
118.3, 101.5, 94.7, 76.7, 73.6, 72.9, 72.0, 69.5, 68.8, 68.0, 67.7,
63.1, 62.1, 52.7, 20.7, 20.6.
4a (Major)
[a]D +26.6 (c = 0.91, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.06 (d, J = 8.0 Hz, 3 H), 7.90 (d,
J = 6.9 Hz, 2 H), 7.72 (d, J = 7.1 Hz, 3 H), 7.69–7.51 (m, 2 H), 7.50–
7.28 (m, 10 H), 7.24 (t, J = 7.8 Hz, 2 H), 7.09 (t, J = 7.4 Hz, 2 H),
6.99 (t, J = 8.0 Hz, 3 H), 6.56 (br s, 1 H), 6.25 (d, J = 7.4 Hz, 2 H),
5.86 (t, J = 9.7 Hz, 1 H), 5.68 (t, J = 9.7 Hz, 1 H), 5.49 (dd, J = 9.9,
8.0 Hz, 1 H), 5.28 (t, J = 9.7 Hz, 1 H), 5.19 (dd, J = 9.9, 3.6 Hz, 1
H), 5.11 (d, J = 8.0 Hz, 1 H), 4.68 (dd, J = 12.2, 2.9 Hz, 1 H), 4.53
(dd, J = 12.4, 5.2 Hz, 1 H), 4.45–4.26 (m, 3 H), 4.23–4.16 (m, 2 H),
4.14–4.03 (m, 2 H), 2.11 (s, 3 H), 2.00 (s, 3 H).
4b (Minor)
1H NMR (300 MHz, CDCl3): d = 8.04 (d, J = 7.1 Hz, 2 H), 7.98 (d,
J = 7.7 Hz, 1 H), 7.88 (d, J = 7.1 Hz, 2 H), 7.72 (d, J = 7.1 Hz, 2 H),
7.68 (d, J = 7.7 Hz, 1 H), 7.61–7.31 (m, 12 H), 7.29–7.05 (m, 7 H),
6.64 (d, J = 7.7 Hz, 2 H), 5.81 (t, J = 9.6 Hz, 2 H), 5.65 (t, J = 9.8
Hz, 1 H), 5.48 (t, J = 8.0 Hz, 1 H), 5.45 (t, J = 7.7 Hz, 1 H), 5.25 (t,
J = 9.3 Hz, 1 H), 5.06 (d, J = 8.0 Hz, 1 H), 4.64 (dd, J = 3.0, 12.4
Hz, 1 H), 4.57–4.85 (m, 2 H), 4.28–4.10 (m, 5 H), 3.70 (br s, 1 H),
2.09 (s, 3 H), 2.00 (s, 3 H).
ESI–MS: m/z = 1024.2 [M + Na+ – C(=NPh)CF3].
ESI–MS: m/z = 1064.3 [M + Na+].
Anal. Calcd for C60H51F3N4O18·H2O: C, 60.51; H, 4.32; N, 4.70.
Found: C, 60.36; H, 4.51; N, 4.43.
Anal. Calcd for C55H51N3O18: C, 63.40; H, 4.93; N, 4.03. Found: C,
63.32; H, 5.02; N, 3.97.
2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl Oleanate (13)
To a solution of oleanolic acid (195 mg, 0.43 mmol) and bromide 3
(377 mg, 1.3 equiv) in CH2Cl2 (5.0 mL) were added K2CO3 (151
mg, 2.5 equiv), water (5.0 mL), and Bu4NBr (56 mg, 0.4 equiv). The
resulting mixture was refluxed for 6 h, and then diluted with
CH2Cl2. The organic phase, after being washed with water and
brine, was dried over Na2SO4, and then concentrated in vacuo. The
residue was purified by a flash column chromatography on silica gel
(toluene–EtOAc, 25:1) to give 13 (398 mg, 90%) as a white foam;
[a]D +67.0 (c = 1.0, CHCl3).
2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-4,6-di-O-
acetyl-2-O-(2-azidomethyl)benzoyl-a/b-D-glucopyranoside (12)
A dark suspension of PdCl2 (165 mg, 0.94 mmol) and compound 11
(1.4 g, 1.34 mmol) in methanol–CH2Cl2 (10 mL:10 mL) was stirred
at r.t. until TLC (petroleum ether–EtOAc, 1.5:1) indicated that the
reaction completed. The mixture was filtered through a bed of
celite. The filtrates were concentrated in vacuo to give a dark syrup,
which was purified by a flash column chromatography on silica gel
(petroleum ether–EtOAc, 2:1) to give 12 (a and b mixture) as a
white solid (1.13 g, 84%).
1H NMR (300 MHz, CDCl3): d = 8.04 (d, J = 7.2 Hz, 2 H), 7.97 (d,
J = 7.5 Hz, 2 H), 7.90 (d, J = 7.2 Hz, 2 H), 7.83 (d, J = 7.2 Hz, 2 H),
7.59–7.28 (m, 12 H), 5.99 (t, J = 9.6 Hz, 1 H), 5.96 (d, J = 8.1 Hz,
1 H), 5.78–5.69 (m, 2 H), 5.28 (s, 1 H), 4.56 (dd, J = 12.3, 3.0 Hz,
1 H), 4.46 (dd, J = 9.3, 5.4 Hz, 1 H), 4.26 (m, 1 H), 3.14 (m, 1 H),
2.79 (m, 1 H), 0.97, 0.94, 0.86, 0.83, 0.76, 0.74, 0.45 (7 × s, 7 ×
CH3).
12a
1H NMR (300 MHz, CDCl3): d = 8.07 (m, 3 H), 7.87 (d, J = 7.1 Hz,
2 H), 7.71 (d, J = 7.4 Hz, 2 H), 7.69–7.30 (m, 13 H), 7.22 (t, J = 7.7
Hz, 2 H), 7.05 (t, J = 7.8 Hz, 2 H), 5.82 (t, J = 9.6 Hz, 1 H), 5.65 (t,
J = 9.6 Hz, 1 H), 5.49 (s, 1 H), 5.46 (t, J = 9.6 Hz, 1 H), 5.15 (t, J =
9.6 Hz, 1 H), 5.10 (d, J = 7.8 Hz, 1 H), 4.97 (dd, J = 10.2, 3.6 Hz, 1
H), 4.70 (d, J = 15.1 Hz, 1 H), 4.64 (dd, J = 12.0, 3.0 Hz, 1 H), 4.50
(dd, J = 12.1, 5.2 Hz, 1 H), 4.44 (t, J = 9.6 Hz, 1 H), 4.23–4.09 (m,
5 H), 3.11 (brs, 1 H), 2.09 (s, 3 H), 1.97 (s, 3 H).
ESI–MS: m/z = 1057.9 [M + Na+].
Anal. Calcd for C64H74O12: C, 74.25; H, 7.21. Found: C, 74.29; H,
7.34.
Synthesis 2004, No. 10, 1641–1647 © Thieme Stuttgart · New York

PAPER
Synthesis of a Typical Glucuronide-Containing Saponin
1645
28-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl Oleanate
3-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-4,6-di-
O-acetyl-2-O-(2-azidomethyl)benzoyl-b-D-glucopyranoside (14)
A mixture of imidate 4 (1.0 g, 0.85 mmol), acceptor 13 (806 mg,
0.78 mmol), and powered 4 Å molecular sieves in anhyd CH2Cl2
was stirred at r.t. under Ar for 1 h. A solution of TMSOTf in CH2Cl2
(0.1 equiv) was added dropwise. After being stirred at r.t. overnight,
the mixture was neutralized with Et3N, and then filtered and con-
centrated. The residue was purified by flash column chromatogra-
phy on silica gel (petroleum ether–EtOAc, 2:1) to give 14 (1.4 g,
89%) as a white solid.; [a]D +40.8 (c = 0.93, CHCl3).
2,3,4,6-Tetra-O-benzoyl-a/b-D-galactopyranosyl N-(Phenyl)tri-
fluoroacetimidate (5)
To a stirred mixture of 2,3,4,6-tetra-O-benzoyl-a/b-D-galactose
(600 mg, 1.0 mmol) and K2CO3 (416 mg, 3.0 mmol) in acetone (20
mL) was added N-(phenyl)trifluoroacetimidoyl chloride (175 mL,
1.2 mmol) under Ar at r.t. After being stirred overnight, the mixture
was filtered. The filtrates were concentrated. The residue was puri-
fied by flash column chromatography on silica gel (petroleum
ether–EtOAc, 5:1) to produce 5 (a/b mixture, 721 mg, 94%) as a
white foam; [a]D +115.6 (5a, c = 1.08, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.08 (d, J = 7.4 Hz, 2 H), 8.03 (d,
J = 7.1 Hz, 2 H), 8.00 (d, J = 7.4 Hz, 2 H), 7.81 (d, J = 7.4 Hz, 2 H),
7.66–7.36 (m, 10 H), 7.28 (t, J = 7.7 Hz, 2 H), 7.12 (t, J = 7.1 Hz, 2
H), 7.02 (t, J = 7.4 Hz, 1 H), 6.89 (br s, 1 H), 6.45 (d, J = 6.6 Hz, 2
H), 6.17 (d, J = 2.2 Hz, 1 H), 6.06 (dd, J = 10.7, 3.0 Hz, 1 H), 5.95
(dd, J = 10.7, 3.3 Hz, 1 H), 4.81 (m, 1 H), 4.65 (dd, J = 11.4, 6.9 Hz,
1 H), 4.44 (dd, J = 11.4, 5.9 Hz, 1 H).
IR (film): 2952, 2104, 1737, 1603, 1585, 1492, 1452, 1369, 1316,
1265, 1178, 1106, 1093, 1069, 1027, 977, 709, 687 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.03 (t, J = 6.9 Hz, 3 H), 7.94 (m,
9 H), 7.67 (t, J = 8.0 Hz, 2 H), 7.58–7.09 (m, 30 H), 5.97 (t, J = 9.8
Hz, 1 H), 5.94 (d, J = 8.2 Hz, 1 H), 5.79–5.68 (m, 3 H), 5.62 (t, J =
9.6 Hz, 1 H), 5.42 (t, J = 8.5 Hz, 1 H), 5.25 (s, 1 H), 5.23 (t, J = 7.7
Hz, 1 H), 5.09 (t, J = 9.5 Hz, 1 H), 5.00 (d, J = 7.7 Hz, 1 H), 4.65
(dd, J = 12.1, 3.0 Hz, 1 H), 4.60–4.40 (m, 5 H), 4.29–4.20 (m, 1 H),
4.19–4.09 (m, 4 H), 4.02 (d, J = 16.2 Hz, 1 H), 3.51 (m, 1 H), 2.89
(dd, J = 11.0, 4.1 Hz, 1 H), 2.78 (d, J = 9.9 Hz, 1 H), 2.07, 1.99, 0.90,
0.84, 0.81, 0.68, 0.48, 0.43, 0.38 (9 × s, 9 × CH3).
13C NMR (75 MHz, CDCl3): d = 165.9, 165.6, 165.5, 165.4, 142.8,
133.7, 133.3, 133.2, 129.9, 129.8, 129.7, 129.3, 128.8, 128.7, 128.6,
128.4, 128.3, 124.4, 119.1, 93.0, 69.8, 68.5, 68.2, 67.6, 62.2.
Anal. Calcd for C42H32F3NO10·1/2H2O: C, 64.95; H, 4.28; N, 1.81.
Found: C, 64.93; H, 4.02; N, 1.62.
13C NMR (75 MHz, CDCl3): d = 175.6, 170.7, 169.2, 166.0, 165.6,
165.1, 164.7, 163.7, 142.9, 139.2, 133.5, 133.2, 133.0, 132.8, 130.4,
129.8, 129.6, 129.5, 129.1, 128.7, 128.4, 128.3, 128.0, 127.6, 127.0,
122.7, 103.0, 101.3, 91.9, 90.3, 79.2, 73.3, 72.9, 72.0, 71.6, 70.3,
69.6, 69.3, 68.8, 63.1, 62.7, 62.5, 55.3, 52.8, 47.4, 46.8, 45.7, 41.5,
40.9, 38.8, 38.5, 38.3, 36.5, 33.7, 32.9, 31.8, 30.5, 29.7, 27.6, 25.6,
25.4, 23.4, 22.6, 20.8, 20.6, 17.9, 16.4, 16.1, 15.1.
28-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl Oleanate
3-O-2,3,4,6-Tetra-O-benzoyl-b-D-galactopyranosyl-(1→2)-
[2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)]-4,6-di-O-
acetyl-b-D-glucopyranoside (16)
A mixture of acceptor 15 (381 mg, 0.20 mmol), donor 5 (472 mg, 3
equiv), and powered 4 Å molecular sieves in anhyd CH2Cl2 (15 mL)
was stirred for 1 h at r.t. under Ar. A solution of TBSOTf in CH2Cl2
(0.2 equiv) was added. The mixture was stirred for 3 h. Et3N was
added, and the mixture was filtered. The filtrates were concentrated
to give a residue, which was applied to a flash column chromatog-
raphy on silica gel (petroleum ether–EtOAc, 5:2–2:1) to provide 16
(447 mg, 90%) as a white solid; [a]D +85.1 (c = 1.13, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.24 (d, J = 7.4 Hz, 2 H), 8.16 (d,
J = 7.4 Hz, 2 H), 8.07 (d, J = 7.4 Hz, 2 H), 8.05–7.78 (m, 18 H),
7.72–7.18 (m, 36 H), 5.98 (t, J = 9.6 Hz, 1 H), 5.94 (d, J = 8.2 Hz,
1 H), 5.87 (t, J = 9.9 Hz, 1 H), 5.78–5.68 (m, 2 H), 5.65–5.06 (m, 2
H), 5.48–5.39 (m, 3 H), 3.27 (s, 1 H), 4.85 (t, J = 9.5 Hz, 1 H), 4.72
(d, J = 7.4 Hz, 2 H), 4.54 (dd, J = 12.2, 2.6 Hz, 1 H), 4.48 (dd, J =
12.2, 4.8 Hz, 1 H), 4.38 (dd, J = 11.3, 6.3 Hz, 1 H), 4.29–4.19 (m, 4
H), 4.18–3.98 (m, 5 H), 3.79 (m, 2 H), 3.35 (m, 1 H), 2.98 (dd, J =
11.5, 4.4 Hz, 1 H), 2.78 (d, J = 11.6 Hz, 1 H), 2.42 (m, 1 H), 2.32 (t,
J = 7.0 Hz, 1 H), 2.04, 1.90, 1.22, 0.99, 0.86, 0.84, 0.79, 0.74, 0.42
(9 × s, 9 × CH3).
13C NMR (75 MHz, CDCl3): d = 175.6, 170.6, 169.3, 166.0, 165.6,
165.5, 165.0, 164.7, 142.9, 134.7, 134.7, 133.5, 133.3, 133.0, 130.2,
129.8, 128.6, 128.3, 122.8, 103.5, 100.1, 91.9, 90.7, 80.0, 72.9,
72.4, 71.3, 70.9, 70.6, 70.4, 69.6, 69.3, 68.6, 67.8, 62.7, 60.6, 55.6,
47.5, 46.8, 45.8, 41.6, 41.0, 39.2, 39.0, 38.6, 36.6, 33.7, 33.0, 31.8,
30.6, 29.7, 27.9, 25.8, 25.5, 23.4, 22.7, 20.8, 18.1, 16.5, 15.2.
ESI–MS: m/z = 2040.8 [M + Na+].
Anal. Calcd for C116H119N3O29·H2O: C, 68.40; H, 5.94; N, 2.06.
Found: C, 68.07; H, 5.69; N, 1.60.
28-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl Oleanate
3-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)-4,6-di-
O-acetyl-b-D-glucopyranoside (15)
To a solution of 14 (1.20 g, 0.60 mmol) in THF (6 mL) at r.t. was
added water (270 mL, 25 equiv), followed by Bu3P (446 mL, 3
equiv). After being stirred for 1 h, the mixture was diluted with
CH2Cl2 and washed with sat. aq NaHCO3 and water. The organic
layer was dried over Na2SO4, and then filtered and concentrated in
vacuo. The residue was purified by flash column chromatography
on silica gel (petroleum ether–EtOAc, 2:1) to yield 15 (995 mg,
90%) as a white foam; [a]D +43.6 (c = 1.0, CHCl3).
IR (film): 3066, 2952, 1737, 1603, 1585, 1492, 1453, 1369, 1317,
1266, 1178, 1094, 1069, 1027, 853, 802, 709, 683, 503 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.07–7.78 (m, 15 H), 7.59–7.18
(m, 25 H), 5.95 (t, J = 9.6 Hz, 1 H), 5.92 (d, J = 8.2 Hz, 1 H), 5.86
(t, J = 9.6 Hz, 1 H), 5.76–5.68 (m, 2 H), 5.66 (t, J = 9.7 Hz, 1 H),
5.45 (dd, J = 9.0, 8.0 Hz, 1 H), 5.25 (s, 1 H), 5.20 (t, J = 8.0 Hz, 1
H), 4.83 (t, J = 9.6 Hz, 1 H), 4.60 (dd, J = 12.2, 2.8 Hz, 1 H), 4.52
(dd, J = 12.4, 2.9 Hz, 1 H), 4.43 (dd, J = 12.2, 4.8 Hz, 2 H), 4.28–
4.16 (m, 2 H), 4.15–3.97 (m, 3 H), 3.76 (t, J = 9.2 Hz, 1 H), 3.49 (m,
1 H), 3.31 (t, J = 7.1 Hz, 1 H), 3.00 (dd, J = 11.5, 4.4 Hz, 1 H), 2.76
(d, J = 11.0 Hz, 1 H), 2.00, 1.87, 0.93, 0.86, 0.82, 0.79, 0.70, 0.66,
0.42 (9 × s, 9 × CH3).
13C NMR (75 MHz, CDCl3): d = 175.7, 170.6, 169.4, 166.0, 165.8,
165.6, 165.1, 164.9, 164.7, 143.0, 133.2, 133.0, 129.9, 129.7, 128.7,
128.4, 128.3, 122.7, 104.5, 101.5, 91.9, 89.9, 81.0, 74.8, 72.9, 72.2,
72.0, 71.6, 70.4, 69.6, 69.3, 68.4, 62.9, 62.7, 62.6, 55.3, 47.4, 46.8,
45.7, 41.5, 40.9, 38.9, 38.8, 38.3, 36.6, 33.7, 32.9, 31.8, 30.5, 28.2,
27.7, 25.6, 25.5, 23.4, 22.6, 20.7, 20.5, 18.1, 16.6, 16.5, 15.1.
HRESI–MS: m/z [M + Na+] calcd for C142H140O37Na: 2459.8966,
found: 2459.8973.
28-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl Oleanate
3-O-2,3,4,6-Tetra-O-benzoyl-b-D-galactopyranosyl-(1→2)-
[2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)]-b-D-glu-
copyranoside (2)
To a solution of 16 (390 mg, 0.16 mmol) in anhyd MeOH (15 mL)
and CH2Cl2 (8 mL) was added acetyl chloride (0.4 mL) at 0 °C. The
solution was stirred at r.t. until TLC (petroleum ether–EtOAc, 1:1)
showed that the starting material disappeared. The solution was
then neutralized with Et3N, and concentrated to dryness. The resi-
due was passed through a short silica gel column (petroleum ether–
HRESI–MS: m/z calcd [M + Na+] for C108H114O28Na: 1881.7389;
found: 1881.7356.
Synthesis 2004, No. 10, 1641–1647 © Thieme Stuttgart · New York

1646
W. Peng et al.
PAPER
EtOAc, 3:2) to give 2 (336 mg, 88%) as a white foam; [a]D +81.4
(c = 0.67, CHCl3).
Methyl 28-O-b-D-Glucopyranosyl Oleanate 3-O-b-D-galactopy-
ranosyl-(1→2)-[b-D-glucopyranosyl-(1→3)]-b-D-glucuronopyr-
anoside (18)
1H NMR (300 MHz, CDCl3): d = 8.29–7.74 (m, 24 H), 7.72–7.18
(m, 36 H), 5.99 (t, J = 9.6 Hz, 1 H), 5.93 (d, J = 8.2 Hz, 1 H), 5.89
(t, J = 9.0 Hz, 1 H), 5.79–5.66 (m, 2 H), 5.64–5.55 (m, 2 H), 5.53–
5.36 (m, 3 H), 5.28 (s, 1 H), 4.79 (dd, J = 11.4, 9.3 Hz, 1 H), 4.69
(dd, J = 11.4, 7.5 Hz, 1 H), 4.59–4.12 (m, 7 H), 4.04 (m, 1 H), 3.92–
3.67 (m, 3 H), 3.59 (t, J = 8.3 Hz, 1 H), 3.50 (t, J = 9.6 Hz, 1 H),
3.44 (s, 1 H), 3.22 (m, 1 H), 3.02 (m, 1 H), 2.79 (m, 1 H), 2.62 (m,
1 H), 2.46 (m, 1 H), 2.33 (m, 1 H), 1.24, 0.99, 0.87, 0.86, 0.83, 0.70,
0.44 (7 × s, 7 × CH3).
13C NMR (75 MHz, CDCl3): d = 175.6, 166.0, 165.9, 165.7, 165.6,
165.3, 165.2, 165.0, 164.9, 164.8, 164.6, 142.8, 133.8, 133.6, 133.4,
133.2, 133.0, 130.2, 129.9, 129.7, 129.5, 129.2, 128.6, 128.5, 128.3,
122.7 103.5, 100.4, 99.8, 91.8, 90.1, 85.8, 74.7, 72.9, 72.1, 71.9,
71.7, 71.0, 70.8, 70.4, 69.5, 69.3, 69.0, 67.6, 63.1, 62.7, 61.8, 60.4,
55.5, 47.4, 46.8, 45.7, 41.5, 40.9, 39.2, 38.9, 38.5, 36.5, 33.7, 32.9,
31.8, 30.5, 27.8, 26.2, 25.4, 25.4, 23.4, 22.7, 18.1, 16.4, 15.1.
To a solution of 17 (43 mg, 18.1 mol) in MeOH–CH2Cl2 (2:1, 9 mL)
was added NaOMe (5% in MeOH, 0.35 mL). The mixture was
stirred for 2 h at r.t., and then neutralized with Dowex 50-X8 (H+)
resin. The resin was filtered off and washed with MeOH. The fil-
trate and washings were combined and concentrated. The residue
was purified with a silica gel column chromatography (CH2Cl2–
MeOH, 3:2) to give 18 (17 mg, 85%) as a white solid; [a]D +20 (c =
0.21, MeOH).
1H NMR (300 MHz, C5D5N–D2O): d = 6.10 (d, J = 7.7 Hz, 1 H),
5.30 (d, J = 7.7 Hz, 1 H), 5.18 (s, 1 H), 5.10 (d, J = 7.4 Hz, 1 H),
4.70 (d, J = 7.1 Hz, 1 H), 4.49 (s, 1 H), 4.45–3.87 (m, 15 H), 3.84–
3.68 (m, 4 H), 3.46 (s, 3 H), 3.0 (m, 2 H), 1.07, 1.02, 0.87, 0.85,
0.68, 0.65, 0.57 (7 × s, 7 × CH3).
13C NMR (100 MHz, C5D5N–D2O): d = 176.6, 170.1, 144.2, 105.3,
104.82, 104.75, 95.9, 89.9, 87.6, 79.4, 79.3, 79.0, 78.7, 76.8, 76.4,
75.5, 74.3, 73.9, 71.8, 71.7, 69.9, 62.4, 61.8, 56.0, 52.3, 47.2, 42.3,
41.9, 40.0, 39.7, 38.8, 37.0, 34.1, 33.3, 32.7, 30.9, 30.6, 30.1, 28.4,
28.2, 26.6, 26.2, 23.9, 23.8, 23.6, 18.9, 17.6, 16.8, 15.7.
ESI–MS: m/z = 2375.5 [M + Na+].
Anal. Calcd for C138H136O35: C, 70.40; H, 5.82. Found: C, 69.72; H,
6.01.
HRESI–MS: m/z [M + Na+] calcd for C55H88O24Na: 1155.5558;
found 1155.5579.
Methyl 28-O-2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl
Oleanate 3-O-2,3,4,6-Tetra-O-benzoyl-b-D-galactopyranosyl-
(1→2)-[2,3,4,6-tetra-O-benzoyl-b-D-glucopyranosyl-(1→3)]-b-
D-glucuronopyranoside (17)
28-O-b-D-Glucopyranosyl Oleanate 3-O-b-D-Galactopyrano-
syl-(1→2)-[b-D-glucopyranosyl-(1→3)]-b-D-glucuronopyra-
noside (1)
A solution of calcium hypochlorite (12 mg, 2 equiv), KBr (1.1 mg,
0.2 equiv), and Bu4NBr (1.0 mg, 0.07 equiv) in sat. aq NaHCO3 (0.7
mL) at 0 °C was added dropwise to a cooled solution of 2 (107 mg,
44.7 mmol, 1.0 equiv) and TEMPO (0.14 mg, 0.02 equiv) in CHCl3
(0.7 mL). The mixture was stirred at 0 °C for 3 h, and then diluted
with water and quenched with Na2SO3.The solution was acidified to
pH = 3 with HOAc and then extracted with EtOAc twice. The or-
ganic phase was washed with brine, dried over Na2SO4, and concen-
trated. The residue was dissolved in THF (1.5 mL). CH2N2 (3.0
equiv) in Et2O (3 mL) was added to the solution at 0 °C. After being
stirred for 0.5 h at 0 °C, the mixture was concentrated to give a res-
idue, which was purified by silica gel column chromatography (2:1
petroleum ether–EtOAc, 2:1) to provide 17 (76 mg, 72%) as a white
foam; [a]D +72.8 (c = 0.91, CHCl3).
1H NMR (300 MHz, CDCl3): d = 8.23–8.16 (m, 4 H), 8.09–7.66 (m,
22 H), 7.64–7.19 (m, 34 H), 5.97 (t, J = 9.6 Hz, 1 H), 5.94 (d, J =
8.5 Hz, 1 H), 5.90 (t, J = 9.8 Hz, 1 H), 5.78–5.69 (m, 2 H), 5.58 (t,
J = 8.4 Hz, 2 H), 5.52–5.43 (m, 2 H), 5.38 (d, J = 3.6 Hz, 1 H), 5.27
(s, 1 H), 4.68 (d, J = 7.7 Hz, 1 H), 4.60 (d, J = 8.0 Hz, 1 H), 4.56
(dd, J = 12.4, 2.8 Hz, 1 H), 4.45 (dd, J = 12.2, 4.8 Hz, 1 H), 4.42–
4.30 (m, 2 H), 4.28–4.16 (m, 2 H), 4.03 (dd, J = 11.0, 7.7 Hz, 1 H),
3.88–3.75 (m, 2 H), 3.78 (s, 3 H), 3.70 (d, J = 9.6 Hz, 1 H), 3.58 (t,
J = 8.6 Hz, 1 H), 3.53 (s, 1 H), 3.02 (dd, J = 15.7, 4.2 Hz, 1 H), 2.78
(d, J = 9.0 Hz, 1 H), 2.62 (m, 1 H), 2.33 (t, J = 6.9 Hz, 1 H), 1.16,
1.02, 0.98, 0.95, 0.86, 0.82, 0.42 (7 × s, 7 × CH3).
Compound 18 (33 mg, 29 mmol) was dissolved in MeOH–CH2Cl2
(2:1, 9 mL), and aq NaOH (0.5 M, 1.2 mL) was added dropwise at
r.t. The resulted solution was stirred for 4 h, and then acidified with
HOAc to pH = 7.0, and with Dowex 50-X8 (H+) resin to pH = 3.0.
The filtrates were concentrated and purified with a silica gel column
chromatography (CH2Cl2–MeOH–H2O, 30:10:1) to give 11 (25 mg,
78%) as a white solid; [a]D +17 (c = 0.39, MeOH).
13C NMR (100 MHz, C5D5N–D2O): d = 178.8, 145.3, 124.4, 105.7,
104.6, 104.4, 96.5, 92.3, 86.8, 79.6, 79.5, 78.7, 78.6, 78.4, 77.8,
75.8, 75.5, 74.5, 74.0, 72.9, 72.0, 71.7, 70.9, 64.7, 63.3, 62.9, 57.0,
49.0, 48.4, 47.44, 43.2, 42.8, 40.9, 40.7, 39.5, 37.9, 35.0, 34.3, 34.1,
33.5, 31.8, 30.8, 29.3, 29.0, 27.2, 24.8, 24.7, 24.4, 19.5, 18.5, 17.7,
16.5.
HRESI–MS: m/z [M + Na+] calcd for C54H86O24Na: 1141.5401;
found 1141.5392.
Acknowledgment
The work described in the paper was supported by the National Na-
tural Science Foundation of China (20172068, 29925203), the
Committee of Science and Technology of Shanghai (01JC14053),
and the Shanghai/Hong Kong/Anson Research Foundation.
13C NMR (75 MHz, CDCl3): d = 175.7, 168.5, 166.1, 165.6, 165.4,
164.9, 164.8, 142.9, 133.5, 133.3, 133.0, 129.8, 129.5, 129.3, 128.6,
128.4, 122.8, 103.8, 100.4, 100.0, 91.9, 90.3, 85.3, 74.8, 72.9, 72.2,
71.9, 71.0, 70.4, 69.9, 69.3, 69.1, 67.6, 62.7, 62.1, 60.6, 55.5, 52.5,
47.5, 46.8, 45.8, 41.5, 41.0, 39.3, 38.9, 36.5, 33.7, 33.0, 31.8, 30.6,
29.7, 27.8, 25.5, 23.4, 22.7, 18.1, 16.4, 15.2.
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