Synthesis of betavulgaroside III, a representative triterpene seco-glycoside

Article abstract of DOI:10.1021/jo800669h

(Chemical Equation Presented) Triterpene seco-glycosides constitute a small family of the plant saponins which feature a terminal seco-saccharide appendage deriving supposedly from oxidative scission of a monosaccharide unit. Herein, we have developed synthetic approaches for the first time to the access to these molecules. Betavulgaroside III (1), a representative congener occurring in Beta vulgaris and Achyranthes fauriei, is successfully synthesized in a total of 31 steps with L-arabinose, D-glucose, and oleanolic acid as starting materials. The longest linear sequence requires 23 steps and in an overall 0.9% yield (from D-glucose). The synthesis features oxidative elaboration of the seco-saccharide unit prior to assembly of the triterpene 3,28-bisglycoside. This tactic has been proven superior, in the attempts to the synthesis of the more easily accessible 2″-epi-betavulgaroside III (2), to that employing oxidative cleavage of the terminal saccharide unit at an advanced triterpene 3,28-bisglycoside scaffold.

Full text of DOI:10.1021/jo800669h

Synthesis of Betavulgaroside III, a Representative Triterpene
seco-Glycoside
Shilei Zhu,† Yingxia Li,† and Biao Yu*,‡
Key Laboratory of Marine Drugs, Marine Drug and Food Institute, Ocean UniVersity of China,
Qingdao 266003, China, and State Key Laboratory of Bio-organic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
byu@mail.sioc.ac.cn
ReceiVed March 26, 2008
Triterpene seco-glycosides constitute a small family of the plant saponins which feature a terminal seco-
saccharide appendage deriving supposedly from oxidative scission of a monosaccharide unit. Herein, we
have developed synthetic approaches for the first time to the access to these molecules. Betavulgaroside
III (1), a representative congener occurring in Beta Vulgaris and Achyranthes fauriei, is successfully
synthesized in a total of 31 steps with L-arabinose, D-glucose, and oleanolic acid as starting materials.
The longest linear sequence requires 23 steps and in an overall 0.9% yield (from D-glucose). The synthesis
features oxidative elaboration of the seco-saccharide unit prior to assembly of the triterpene 3,28-
bisglycoside. This tactic has been proven superior, in the attempts to the synthesis of the more easily
accessible 2′′-epi-betavulgaroside III (2), to that employing oxidative cleavage of the terminal saccharide
unit at an advanced triterpene 3,28-bisglycoside scaffold.
Introduction
compounds, make the isolation and structure elucidation
extremely difficult. In fact, most of these compounds have
been isolated after derivatization (e.g., methyl ester forma-
tion), and their stereochemistry in the terminal fragment
remains unsolved. Another intriguing structural feature of
the triterpene seco-glycosides is their mimicry of the sialyl
Lewis X (sLex) structure,6 a cell surface saccharide epitope
with significance biological functions. In fact, a mixture of
the triterpene seco-glycosides from A. fauriei showed inhibi-
tory activities against the excess recruiting of neutrophiles
to injured tissues 1000 times more potently than sLex.1c To
explore synthetic approaches to the access to this type of
interesting molecules, in conjugation with our long efforts
on the synthesis of saponins,7 we chose betavulgaroside III
(1, Figure 1) as the first target of the triterpene seco-
glycosides. This molecule, isolated from B. Vulgaris2a–c and
A. fauriei (as a trimethyl ester derivative),1b is a representative
congener whose stereochemistry has been determined by
correlation between common derivatives from known com-
Since 1994, Ida,1 Yoshikawa,2 Connolly,3 Bourdy,4 Lacaille-
Dubois,5 and their co-workers have disclosed over 20
triterpene seco-glycosides from six edible plants, i.e., Achy-
ranthes fauriei, Achyranthes bidentata, Beta Vulgaris (sugar
beet), Spinacia oleracea (spinach), Basella rubra (Indian
spinach), and Pisonia umbellifera. These novel saponins
feature virtually an oxidative fragmentation of a terminal
monosaccharide unit. The resulting acetal and carboxylic acid
functions, together with the scarce occurrence of these
* To whom correspondence should be addressed. Fax: (86)21-64166128.
† Ocean University of China.
‡ Shanghai Institute of Organic Chemistry.
(1) (a) Ida, Y.; Satoh, Y.; Katoh, M.; Katsumata, M.; Nagasao, M.;
Yamaguchi, K.; Kamei, H.; Shoji, J. Tetrahedron Lett. 1994, 35, 6887. (b) Ida,
Y.; Satoh, Y.; Katsumata, M.; Nagasao, M.; Shoji, J. Chem. Pharm. Bull. 1995,
43, 896. (c) Ida, Y.; Satoh, Y.; Katsumata, M.; Nagasao, M.; Hirai, Y.; Kajimoto,
T.; Katada, N.; Yasuda, M.; Yamamoto, T. Bioorg. Med. Chem. Lett. 1998, 8,
2555. (d) Ando, H.; Fukumura, M.; Hori, Y.; Hirai, Y.; Toriizuka, K.; Kuchino,
Y.; Ida, Y. J. Nat. Med. 2008, 62, 57.
4978 J. Org. Chem. 2008, 73, 4978–4985
10.1021/jo800669h CCC: $40.75 2008 American Chemical Society
Published on Web 06/05/2008

Synthesis of BetaVulgaroside III
SCHEME 1. Preparation of Monosaccharide Donors 5 and
7
linkage could be constructed stereoselectively by glycosylation
with an arabinose donor equipped with a participating group at
its 2-OH and the 3,4-cis-diol could be differentially protected
with an acetal group. From this precursor, the 2′′-epi-betavul-
garoside III (2) turned out to be a straightforward target.
Therefore, we explored the synthetic route toward 2 before
elaboration of the target natural saponin 1.
First-Generation Synthesis of 2′′-epi-Betavulgaroside
III (2). We have developed an efficient approach to the synthesis
of oleanane-type triterpene 3,28-O-bisglycosides with ꢀ-D-
glucuronide as the first monosaccharide unit attaching at the
3-OH.9 Adopting modification of a similar synthetic sequence,
the preparation of a trisaccharide precursor such as 15 met with
no difficulty (Scheme 2). The required monosaccharide building
blocks, i.e., 2,4-di-O-benzoyl-3-O-benzyl-6-O-trityl-D-glucopy-
ranosyl trichloroacetimidate (5) and phenyl 3,4-O-isopropy-
lidene-2-O-benzoyl-1-thio-R-L-arabinopyranoside (7), both
equipped with a neighboring participating benzoyl group at the
2-OH, were readily prepared using routing transformations as
shown in Scheme 1.
FIGURE 1. Betavulgaroside III (1), 2′′-epi-betavulgaroside III (2), and
the retrosynthetic perspective.
pounds.2c Herein, we report our synthetic studies toward
betavulgaroside III (1).
Results and Discussion
Coupling of oleanolic acid (8) with 2,3,4,6-tetra-O-benzoyl-
R-D-glucopyranosyl bromide (9) under the optimized phase-
transfer-catalyzed conditions (K2CO3, Bu4NBr, CH2Cl2-H2O,
reflux) gave the 28-ꢀ-glucosyl ester 10 (89%; H-1′, 5.96 ppm,
d, J ) 8.1 Hz).9,12 The remaining oleanane 3-OH was glyco-
sylated with glucosyl imidate 5 in the presence of TBSOTf (0.1
equiv) to provide the 3-O-ꢀ-glucoside 11 in an excellent 92%
yield (H-1′, 4.93 ppm, d, J ) 7.5 Hz). Selective removal of the
3′-O-benzyl group in 11 via hydrogenolysis over Pd/C was
unsuccessful, but leading to the complete cleavage of the 6′-
O-trityl group as well (24 h) to afford 3′,6′-diol 12 (93%). The
primary 6′-OH in 12 was then selectively protected with a TBS
Betavulgaroside III (1) would be derived from oleanane
trisaccharide A via an oxidative scission of the vicinal 3,4-diol
in the terminal pentose unit (Figure 1). The pentose unit should
be in a form of 1,2-cis-R-L-pentopyranoside or 1,2-cis-ꢀ-D-
pentopyranoside to meet the final stereochemistry requirement.
However, direct construction of such a 1,2-cis-glycoside linkage
is not a trivial task. A feasible alternative would be assembly
of a 1,2-trans-glycoside followed by inversion of the 2-OH
configuration.8 Thus, R-L-arabinopyranoside (i.e., B) became a
choice of the precursor, where the 1,2-trans-R-L-pyranosidic
(2) (a) Yoshikawa, M.; Murakami, T.; Kadoya, M.; Matsuda, H.; Yamahara,
J.; Muraoka, O.; Murakami, N. Heterocycles 1995, 41, 1621. (b) Yoshikawa,
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J. D.; Sheeley, D. M. Phytochemistry 1994, 37, 1667.
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B.; Lacaille-Dubois, M.-A. J. Nat. Prod. 2001, 64, 243. (b) Mitaine-Offer, A.-
C.; Marouf, A.; Hanquet, B.; Birlirakis, N.; Lacaille-Dubois, M.-A. Chem. Pharm.
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6107.
J. Org. Chem. Vol. 73, No. 13, 2008 4979

Zhu et al.
SCHEME 2. Linear Assembly of the Trisaccharide Precursor 15
1
ether to provide 13 (97%). Condensation of the 3′-OH (in 13)
with thioarabinoside 7 under the action of NIS and TMSOTf
(and AgOTf as well)13 led to the desired R-L-arabinopyranoside
14 in only moderate yields (<70%), due to the partial cleavage
of the 6′-O-TBS ether. Nevertheless, the combination of NIS
poorly diagnostic H NMR spectrum. Thus, the product was
subjected to methyl ester formation (CH2N2, EtOAc, rt);
subsequent separation (on silica gel) led to two major com-
pounds. The expected tris-methyl ester 16 was obtained in 43%
yield (H-12, 5.24 ppm, s; C-12, 122.7 ppm), while the other
product in 39% yield was determined to be the 11-one derivative
17 (H-12, 5.61 ppm, s; H-9, 2.9 ppm, d-like; C-11, 199.8 ppm;
C-12, 128.1 ppm). The oxidation of the allylic 11-CH2 of an
oleanane derivative was not without precedent.18 Alkaline
removal of the benzoyl and methyl esters in 16 was found to
be problematic. Treatment of 16 with NaOH (THF, MeOH,
H2O, rt) for 24 h led to the complete consumption of the starting
16. Repeated chromatography of the resulting mixture on ODS-
silica gel (MeOH-H2O-TFA, 6:2:0.024) failed to give a
homogeneous product. Thus, the collected mixture was treated
with CH2N2 (MeOH–EtOAc, rt) to provide the methyl esters,
which could be separated by silica gel (CH2Cl2-EtOAc, 1:1).
The expected tris-methyl ester 18 was isolated as a major
product in 46% yield. The other three minor products isolated
were determined by 1H NMR analysis to be the degraded
compounds D, E,19 and F,20 indicating cleavage of the 28-
glucosyl ester linkage (under alkaline conditions) and the
terminal acetal moiety (likely under the acid treatment during
chromatography on ODS-silica gel) could take place. Finally,
removal of the methyl esters in 18 was effected with K2CO3 in
14
and BF3OEt2 as promoter was able to provide 14 in a
satisfactory 81% yield. Treatment of the oleanane trisaccahride
14 with TsOH ·H2O in CH2Cl2/MeOH at rt effected removal of
both the 2′′,3′′-O-isopropylidene and the 6′-O-TBS group,
providing triol 15 in 88% yield.
The advanced trisaccahride precursor 15 was then subjected
to oxidative cleavage of the 2′′,3′′-diol (Scheme 3). Treatment
of 15 with Pd(OAc)4 (in toluene or CH3CN at rt) led to sluggish
reaction.2c,f,15 Using aq NaIO4 as an oxidant,16 the reaction (in
CHCl3 or THF at rt) proceeded faster; upon raising the
temperature to 60 °C, the reaction completed within 2 h. The
resulting hydrated bisaldehyde, and the 6′-OH as well, was
further oxidized with the Jones reagent17 to give supposedly
the corresponding tris-carboxylic acid C. However, the product
purified by careful chromatography on silica gel and ODS-silica
gel was shown to be heterogeneous by an acquirement of a
(13) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron Lett. 1990,
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Lett. 2003, 44, 1417.
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S. Tetrahedron: Asymmetry 2005, 16, 995. (b) Yeo, J. E.; Yang, X.; Kim, H. J.;
Koo, S. Chem. Commun. 2004, 236.
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P.; Vigassy, T.; Clark, D. D.; Hussey, S. L.; Peter, M.; Peterson, B. R.; Pretsch,
E.; Walde, P.; Carreira, E. M. Angew. Chem., Int. Ed. 2004, 43, 5181. (b) Smith,
A. B.; Han, Q.; Breslin, P. A. S.; Beauchamp, G. K. Org. Lett. 2005, 7, 5075.
(c) Sumi, S.; Matsumoto, K.; Tokuyama, H.; Fukuyama, T. Tetrahedron 2003,
59, 8571. (d) Sumi, S.; Matsumoto, K.; Tokuyama, H.; Fukuyama, T. Org. Lett.
2003, 5, 1891.
(18) (a) Zaprutko, L.; Partyka, D.; Bednarczyk-Cwynar, B. Bioorg. Med.
Chem. Lett. 2004, 14, 4723. (b) Honda, T.; Finlay, H. J.; Gribble, G. W.; Suh,
N.; Sporn, M. B. Bioorg. Med. Chem. Lett. 1997, 7, 1623. (c) Corey, E. J.;
Ursprung, J. J. J. Am. Chem. Soc. 1956, 78, 184.
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Satake, M. Chem. Pharm. Bull. 1989, 37, 2318. (b) Nagao, T.; Tanaka, R.; Okabe,
H. Chem. Pharm. Bull. 1991, 39, 1699.
(17) (a) Billing, J. F.; Nilsson, U. J. Tetrahedron 2005, 61, 863. (b) Billing,
J. F.; Nilsson, U. J. Tetrahedron Lett. 2005, 46, 991. (c) Jarosz, S.; Mach, M.;
Frelek, J. J. Carbohydr. Chem. 2000, 19, 693.
(20) (a) Hu, M.; Ogawa, K.; Sashida, Y.; Xiao, P.-G. Phytochemistry 1995,
39, 179. (b) Shimizu, S.; Ishihara, N.; Umehara, K.; Miyase, T.; Ueno, A. Chem.
Pharm. Bull. 1988, 36, 2466.
4980 J. Org. Chem. Vol. 73, No. 13, 2008

Synthesis of BetaVulgaroside III
SCHEME 3. Completion of the First-Generation Synthesis of 2′′-epi-Betavulgaroside III (2)
a mixed solvent of CH3CN and H2O,2b affording the desired
2′′-epi-betavulgaroside III (2) in a good 88% yield.
bearing a free 3-OH in good yield (77% for three steps).
Glycosylation of 21 with thioarabinoside 7 under the action of
NIS and AgOTf was able to afford the R-L-arabinosyl-(1f3)-
glucuronide 22 in a high 87% yield (H-1′, 4.85 ppm, d, J ) 5.7
Hz). The 3′,4′-O-isopropylidene group in 22 was removed with
TsOH·H2O, giving diol 23 (78%). Treatment of 23 with NaIO4
(THF, H2O, 60 °C), followed by further oxidation of the
resulting bis-aldehyde with NaClO2 and NH2SO3H,2f and
subsequent benzyl ester formation (BnBr, NaHCO3, DMF)
afforded the tris-benzyl ester 24 in an excellent 88% yield.
Removal of the anomeric O-acetyl group was effected with
BnNH2 (THF, rt),22 the resulting lactol was condensed with
NCCCl3 (DBU, CH2Cl2) to provide the desired seco-disaccha-
ride trichloroacetimidate 25 in 98% yield.
Replacement of the previous benzoyl protecting groups in
the 28-glucose unit with acetyl groups would further facilitate
the final deprotection. Thus, peracetyl glucosyl R-bromide 26,12
in stead of the perbenzoyl counterpart 9, was used to couple
with oleanolic acid (8) under the similar phase-transfer-catalyzed
conditions to provide the 28-ꢀ-glucosyl ester 27 (78%; H-1′,
5.57 ppm, d, J ) 7.8 Hz) (Scheme 5). Condensation of 27 with
Second-Generation Synthesis of 2′′-epi-Betavulgaroside
III (2). The above synthetic approach compromised with two
low-yielding transformations: one was the oxidation of triol 15
(to give tris-carboxylic acid C); another was the final removal
of the methyl and benzoyl protecting groups (16 f 2). Thus,
we decided to elaborate the ester function in the 3-O-saccharide
moiety before connecting to the oleanane aglycon to avoid the
oxidation of the allylic 11-CH2. In addition, benzyl group was
chosen to protect the carboxylic acid function to facilitate the
final removal (via hydrogenolysis).
The required seco-disaccharide donor 25 was prepared as
shown in Scheme 4. Thus, treatment of the previous available
glucosyl imidate 5 with HOAc and TMSOTf (0.1 equiv)
provided 1-ꢀ-acetate 19 (95%; H-1, 5.94 ppm, d, J ) 8.1 Hz).
Removal of the 6-O-trityl group (in 19) with TsOH ·H2O
provided 20 (78%), compromised with the partial cleavage of
the 1-O-acetyl group. Compound 20 was subjected to oxidation
with Jones reagent to generate the 6-carboxylic acid function;
subsequent removal of the 3-O-benzyl group with NaBrO3 and
Na2S2O4 (EtOAc, H2O, rt)21 followed by benzyl ester formation
(BnBr, NaHCO3, DMF, 50 °C) furnished benzyl uronate 21
(22) (a) Lohman, G. J. S.; Hunt, D. K.; Hoegermeier, J. A.; Seeberger, P. H.
J. Org. Chem. 2003, 68, 7559. (b) Orgueira, H. A.; Bartolozzi, A.; Schell, P.;
Litjens, R. E. J. N.; Palmacci, E. R.; Seeberger, P. H. Chem. Eur. J. 2003, 9,
140.
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1999, 40, 8439.
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Zhu et al.
SCHEME 4. Preparation of the seco-Disaccharide Donor 25
SCHEME 5. Completion of the Second-Generation Synthesis of 2′′-epi-Betavulgaroside III (2)
the seco-disaccharide imidate 25 under the normal conditions
(0.1 equiv TBSOTf, CH2Cl2, 0 °C-rt) afforded the desired 3-O-
ꢀ-glucuronide 28 in 67% yield (H-1′, 4.67 ppm, d, J ) 7.5 Hz).
Finally, the three benzyl groups were cleaved cleanly via
hydrogenolysis over Pd(OH)2 (i-PrOH, EtOAc, rt), and the four
acetyl and three benzoyl groups were removed with NaOMe
(THF, MeOH, rt). Acidification of the resulting mixture with
H+ resin and chromatography on ODS-silica gel (MeOH-
H2O-TFA, 6:2:0.024) afforded the 2′′-epi-betavulgaroside III
(2) in a good 68% yield.
Synthesis of Betavulgaroside III (1). Adopting the above
approach to the synthesis of the natural betavulgaroside III (1)
would require the preparation of seco-disaccharide donor 36
(Scheme 6), the 2′-epimer of the previous disaccharide donor
25. The synthesis of 36, shown in Scheme 6, involved reversion
of the 2′-OH configuration on the R-L-arabinopyranosyl unit of
the disaccharide 32. To prepare 32, a protecting group capable
of neighboring participation and of being selectively removable
in the presence of esters should be installed in the arabinose
building block. The 2-(azidomethyl)benzoyl (AZMB) group
turned out to be the choice.9,23 Thus, phenyl 2-O-AZMB-3,4-
O-isopropylidene-1-thioarabinopyranoside 29 was prepared
(from 6, 92%) and coupled with glucuronide 30, which was
prepared readily from 4 (four steps, 21% yield for the R-anomer;
cf. 19f21). Under the promotion of NIS and AgOTf, the
coupled disaccharide 31 was obtained in a good 81% yield (H-
1′, 4.95 ppm, d, J ) 5.4 Hz). The 2′-O-AZMB group in 31 was
then selectively taken off with Ph3P (THF, H2O, rt) to provide
32 (88%; H-1′, 4.43 ppm, d, J ) 6.9 Hz). The resulting
equatorial 2′-OH in 32 was successfully reversed via oxidation
(Dess-Martin periodine, CH2Cl2, 50 °C) and subsequent reduc-
tion (NaBH4, CH2Cl2-EtOAc-MeOH, 0 °C) to furnish the R-L-
ribopyranoside 33 in a good 74% yield (H-1′, 4.99 ppm, d, J )
4.8 Hz).8 Worth noting is that we had prepared a 1-O-acetyl
counterpart of the 1-O-benzoyl disaccharide 32 from arabinose
29 and the previously available glucuronide 21, however, the
1-O-acetyl group could not survive during the reduction. The
axial 2′-OH in 33 was protected with benzoyl group (BzCl,
DMAP, pyridine, 50 °C) and the 3′,4′-O-isopropylidene group
was removed (TsOH ·H2O, CH2Cl2, MeOH, rt), providing 34
(81%). 3′,4′-Diol 34 was then subjected to the sequence of
oxidative cleavage (NaIO4, THF-H2O, 60 °C), further oxidation
of the resulting aldehyde to carboxylic acid (NaClO2,
NH2SO3H), and subsequent benzyl ester formation (cf. 23 f
24) to furnish the tris-benzyl ester 35 in a satisfactory 75% yield.
Selective removal of the anomeric benzoyl group in 35 was
found to be difficult, comparing to the removal of the anomeric
(23) (a) Wada, T.; Ohkubo, A.; Mochizuki, A.; Sekine, M. Tetrahedron Lett.
2001, 42, 1069. (b) Love, K. R.; Andrade, R. B.; Seeberger, P. H. J. Org. Chem.
2001, 66, 8165. (c) Tang, P.; Yu, B. Angew. Chem., Int. Ed. 2007, 46, 2527.
4982 J. Org. Chem. Vol. 73, No. 13, 2008

Synthesis of BetaVulgaroside III
SCHEME 6. Preparation of the seco-Disaccharide Donor 36
SCHEME 7. Completion of the Total Synthesis of Betavulgaroside III (1)
acetyl group in 24. Thus, treatment of 35 with N2H4 ·AcOH in
DMF at rt afforded the lactol in moderate yield,24 which was
directly converted into the desired trichloroacetimidate 36 (48%).
Coupling of the seco-disaccharide imidate 36 with the
3-hydoxyl-oleanane-28-ester 27 under similar conditions for the
coupling of 25 and 27 (Scheme 5, TBSOTf, CH2Cl2, 0 °C to
rt) gave the coupled product 37 in a good 75% yield (Scheme
7). Finally, the three benzyl groups were cleaved cleanly via
hydrogenolysis over Pd/C; the subsequent removal of the
benzoyl and acetyl groups was found to be more effective with
LiOH in a mixed solvent of CH2Cl2, MeOH, and H2O (cf. with
NaOMe for 28 f 2, Scheme 5), furnishing the target molecule
1 in a good 85% yield. The analytical data of the synthetic 1
are in good accordance with those reported for the natural
product.25
the access to these molecules. Betavulgaroside III (1), a
representative congener with its stereochemistry having been
determined, is successfully synthesized in a total of 31 steps
with L-arabinose, D-glucose, and oleanolic acid as starting
materials. The longest linear sequence requires 23 steps and in
an overall yield of 0.9% (from D-glucose). The synthesis features
elaboration of the seco-saccharide unit prior to assembly of the
triterpene 3,28-bisglycoside. This strategy has been proven
superior to a latter oxidative elaboration of the seco-saccharide
unit at the triterpene 3,28-bis-glycoside scaffold in the attempts
to the synthesis of the more easily accessible 2′′-epi-betavul-
garoside III (2).
Experimental Section
For the synthesis of compounds 4, 5, 7, 11-25, 29, and 30, see
the Supporting Information.
Conclusion
2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl Oleanate (27). To
a solution of oleanolic acid 8 (2.3 g, 5.0 mmol) and glucosyl
bromide 26 (2.7 g, 1.3 equiv) in CH2Cl2 (100 mL) were added
K2CO3 (8.7 g, 1.2 equiv), water (65 mL), and Bu4NBr (170 mg,
0.1 equiv). The resulting mixture was refluxed for 6 h and was
then diluted with CH2Cl2. The organic phase, after being washed
with water and brine, respectively, was dried over Na2SO4 and then
concentrated in vacuo. The residue was purified by column
Triterpene seco-glycosides constitute a small family of the
plant saponins, which feature a terminal seco-saccharide ap-
pendage deriving supposedly from oxidative fragmentation of
a monosaccharide unit. These novel structures might present
interesting bioactivities, such as the anti-inflammatory activities
via mimicry of the sLex structure. The nascent acetal and
carboxylic acid functions in the triterpene seco-glycosides make
the isolation and structure elucidation extremely difficult. Herein,
we have developed synthetic approaches for the first time to
chromatography on silica gel (petroleum ether-EtOAc, 4:1) to give
1
27 (3.07 g, 78%) as a white foam: [R]27 37.5 (c 1.3, CHCl3); H
D
NMR (300 MHz, CDCl3) δ 5.57 (d, J ) 7.8 Hz, 1H), 5.31-5.09
(m, 4H), 4.27 (dd, J ) 12.3, 4.5 Hz, 1H), 4.07-4.01 (m, 1H),
3.81-3.75 (m, 1H), 3.22-3.17 (m, 1H), 2.82-2.78 (m, 1H), 2.06
(s, 3H), 2.01 (s, 6H), 2.00 (s, 3H), 1.11 (s, 3H), 0.97 (s, 3H), 0.89
(s, 6H), 0.77 (s, 3H), 0.72 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
(24) Coutant, C.; Jacquinet, J.-C. J. Chem. Soc. Perkin Trans. 1 1995, 1573.
(25) A comparison of the NMR spectra of the synthetic 1, 2, and the natural
product is given in the Supporting Information.
J. Org. Chem. Vol. 73, No. 13, 2008 4983

Zhu et al.
175.5, 170.5, 170.0, 169.3, 168.8, 142.7, 122.7, 91.4, 78.7, 72.7,
69.7, 67.8, 61.3, 55.0, 47.4, 46.6, 45.6, 41.5, 40.8, 39.1, 38.6, 38.3,
36.8, 33.6, 32.9, 32.7, 31.6, 30.5, 27.9, 27.6, 27.0, 25.5, 23.3, 23.2,
22.7, 20.6, 20.5, 18.1, 16.8, 15.5, 15.2; HRMS (MALDI) calcd for
C44H66O12Na [M + Na]+ 809.4447, found 809.4449.
1H), 5.07 (ABq, J ) 12.0 Hz, 2H), 4.95 (d, J ) 5.4 Hz, 1H), 4.72
(t, J ) 9.9 Hz, 1H), 5.05 (ABq, J ) 15.0 Hz, 2H), 4.27 (dd, J )
13.5, 6.3 Hz, 1H), 4.11 (t, J ) 7.2 Hz, 1H), 3.61 (dd, J ) 12.0, 7.5
Hz, 1H), 3.41 (dd, J ) 12.3, 6.3 Hz, 1H), 1.38 (s, 3H), 1.23 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 167.0, 165.1, 164.5, 164.4,
163.9, 137.9, 134.2, 133.8, 133.5, 133.1, 132.6, 130.7, 129.9, 129.3,
129.1, 128.7, 128.6, 128.4, 128.3, 128.3, 128.1, 127.5, 111.0, 100.1,
89.5, 74.8, 74.8, 72.6, 71.5, 70.9, 70.2, 68.1, 61.4, 52.7, 27.3, 25.7;
HRMS (MALDI) calcd for C50H45N3O15Na [M + Na]+ 950.2743,
found 950.2765.
3,4-O-Isopropylidene-r-L-arabinopyranosyl-(1f3)-[benzyl1,2,4-
tri-O-benzoyl-r-D-glucuronopyranoside] (32). To a solution of
31 (173 mg, 0.19 mmol) in THF (3 mL) at rt was added water (36l
10 equiv), followed by Ph3P (150 mg, 3 equiv). After being stirred
overnight, the mixture was concentrated in vacuo. The residue was
purified by column chromatography on silica gel (petroleum
Tris-benzyl Ester 28. A mixture of the glycosyl imidate 25 (22
mg, 0.02 mmol), acceptor 27 (31 mg, 1.5 equiv), and powered 4 Å
molecular sieves in anhyd CH2Cl2 (5 mL) was stirred at rt under
Ar for 1 h. A solution of TBSOTf in CH2Cl2 (0.1 equiv) was at 0
°C added dropwise. After being stirred at rt for 1 h, the mixture
was neutralized with Et3N, filtered, and concentrated. The residue
was purified by column chromatography on silica gel (petroleum
ether-EtOAc, 3:1) to give 28 (27 mg, 67%) as a white foam: [R]25
D
1
-0.6 (c 1.6, CHCl3); H NMR (300 MHz, CDCl3) δ 8.04-7.12
(m, 30H), 5.65-5.56 (m, 2H), 5.46 (t, J ) 8.4 Hz, 1H), 5.38-5.34
(m, 3H), 5.25-5.09 (m, 5H), 5.04-4.90 (m, 4H), 4.76 (t, J ) 9.0
Hz, 1H), 4.67 (d, J ) 7.5 Hz, 1H), 4.31-4.18 (m, 2H), 4.10-3.77
(m, 4H), 3.09-3.04 (m, 1H), 2.85-2.78 (m, 1H), 2.06 (s, 3H),
2.02 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.08 (s, 3H), 0.90 (s, 6H),
0.86 (s, 3H), 0.69 (s, 3H), 0.63 (s, 3H), 0.59 (s, 3H);13C NMR (75
MHz, CDCl3) δ 175.5, 170.6, 170.1, 169.5, 169.4, 168.9, 167.0,
166.0, 165.4, 164.8, 164.6, 142.7, 135.2, 134.9, 134.7, 133.2, 133.0,
132.8, 130.0, 129.7, 129.6, 129.3, 128.6, 128.5, 128.3, 128.2, 128.2,
128.0, 127.9, 122.8, 103.0, 100.0, 91.5, 90.1, 77.4, 77.2, 77.0, 76.6,
75.9, 73.5, 72.7, 72.3, 71.7, 70.4, 69.8, 67.8, 67.4, 67.0, 66.5, 62.7,
61.4, 55.3, 47.4, 46.7, 45.6, 41.5, 40.9, 39.1, 38.6, 36.5, 33.6, 32.9,
31.6, 30.5, 29.6, 27.6, 25.5, 23.4, 22.6, 20.6, 20.5, 16.8, 16.0, 15.2;
HRMS (MALDI) calcd for C97H110O27Na [M + Na]+ 1729.7127,
found 1729.7161.
ether-CH2Cl2-EtOAc, 5:3:2) to yield 32 (126 mg, 88%) as a white
1
solid: [R]23 59.8 (c 0.8, CHCl3); H NMR (300 MHz, CDCl3) δ
D
8.11-6.81 (m, 20H), 6.80 (d, J ) 3.6 Hz, 1H), 5.68-5.57 (m,
2H), 5.16 (d, J ) 12.3 Hz, 1H), 5.00 (d, J ) 12.3 Hz, 1H), 4.73
(d, J ) 9.9 Hz, 1H), 4.56 (t, J ) 9.3 Hz, 1H), 4.43 (d, J ) 6.9 Hz,
1H), 4.11-4.04 (m, 1H), 3.80 (t, J ) 7.8 Hz, 1H), 3.52 (m, 1H),
3.40 (dd, J ) 5.7, 12.3 Hz, 1H), 3.22 (dd, J ) 5.1, 12.3 Hz, 1H),
1.38 (s, 3H), 1.21 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.0,
165.6, 165.0, 164.0, 134.1, 133.9, 133.5, 133.3, 129.9, 129.8, 129.7,
129.2, 128.7, 128.6, 128.4, 128.4, 128.3, 128.3, 110.3, 103.4, 89.7,
76.9, 76.8, 73.1, 71.9, 71.0, 70.9, 70.2, 68.0, 62.3, 27.4, 25.3; HRMS
(MALDI) calcd for C42H40O14Na [M + Na]+ 791.2311, found
791.2329.
2′′-epi-Betavulgaroside III (2). Compound 28 (40 mg, 0.023
mmol) was treated with Pd(OH)2/C (cat.) under 1 atm of H2 in
i-PrOH-EtOAc (4 mL:2 mL) for 5 h. The mixture was then filtered.
The filtrate was concentrated and dissolved in THF-MeOH (2 mL:2
mL). To this solution was added NaHCO3 (6 mg, 3 equiv) at rt.
After being stirred for 1 h, NaOMe (cat.) was added to the solution.
The resulting mixture was stirred until TLC (CH2Cl2-MeOH-H2O,
5:4:1) indicated that the reaction completed and was then acidified
with Dowex 50-X8 (H+) resin to pH ) 3.0. The filtrates were
concentrated and purified with reversed-phase ODS column chro-
3,4-O-Isopropylidene-r-L-ribopyranosyl-(1f3)-[benzyl 1,2,4-
tri-O-benzoyl-r-D-glucuronopyranoside] (33). To a solution of
32 (23 mg, 0.03 mml) in CH2Cl2 (3 mL) was added NaHCO3 (10
mg, 4 equiv) and the Dess-Martin reagent (40 mg, 3 equiv). The
resulting mixture was stirred at 50 °C for 2 h and then diluted with
EtOAc. The organic phase, after being washed with aqueous 10%
Na2S2O3, saturated aqueous NaHCO3, and brine, respectively, was
dried over Na2SO4 and then concentrated in vacuo to give the crude
ketone as a white solid. The crude ketone was dissolved in
CH2Cl2-EtOAc-MeOH (1 mL:0.5 mL:0.5 mL), followed by
addition of NaBH4 (1.5 mg, 1.5 equiv) at 0 °C. After being stirred
for 0.5 h at 0 °C, the mixture was neutralized with 1 N HCl and
diluted with EtOAc. The organic phase, after being washed with
saturated aqueous NaHCO3 and brine, respectively, was dried over
Na2SO4 and concentrated. Chromatography over silica gel (petro-
leum ether-CH2Cl2-EtOAc, 5:3:2) gave 33 (17 mg, 74%) as a
white solid: [R]23D 20.9 (c 0.8, CHCl3); 1H NMR (300 MHz, CDCl3)
δ 8.10-6.79 (m, 20H), 6.78 (d, J ) 3.6 Hz, 1H), 5.73-5.63 (m,
2H), 5.16 (d, J ) 11.7 Hz, 1H), 4.99 (d, J ) 4.8 Hz, 1H), 4.92 (d,
J ) 11.7 Hz, 1H), 4.68 (d, J ) 7.5 Hz, 1H), 4.60 (t, J ) 9.6 Hz,
1H), 4.19 (t, J ) 4.5 Hz, 1H), 3.98-3.95 (m, 1H), 3.57-3.53 (m,
1H), 3.46-3.39 (m, 1H), 3.01-2.94 (dd, J ) 6.9, 11.7 Hz, 1H),
2.38 (d, J ) 11.7 Hz, 1H), 1.40 (s, 3H), 1.23 (s, 3H);13C NMR (75
MHz, CDCl3) δ 167.0, 165.3, 165.2, 164.0, 134.0, 133.9, 133.5,
133.4, 129.9, 129.8, 129.6, 129.0, 128.9, 128.7, 128.6, 128.5, 128.4,
128.3, 127.5, 126.9, 110.2, 99.0, 89.6, 73.4, 71.2, 70.9, 70.4, 68.2,
66.0, 65.2, 58.0, 27.9, 26.0; HRMS (MALDI) calcd for
C42H40O14Na [M + Na]+ 791.2310, found 791.2307.
2-O-Benzoyl-r-L-ribopyranosyl-(1f3)-[benzyl 1,2,4-tri-O-
benzoyl-r-D-glucuronopyranoside] (34). Compound 33 (23 mg,
0.03 mmol) was dissolved in dry pyridine (2 mL), and BzCl (0.01
mL, 3 equiv) was added under an Ar atmosphere at rt. The mixture
was stirred at 50 °C for 1 h and was then concentrated and diluted
with EtOAc. The organic phase, after being washed with aqueous
1 N HCl, saturated aqueous NaHCO3, and brine, respectively, was
dried over Na2SO4 and then concentrated in vacuo to give the crude
product as a yellow oil. To the solution of the crude product in
MeOH-CH2Cl2 (2 mL:4 mL) was added p-TsOH·H2O (18 mg, 3
equiv). After being stirred at rt until TLC (petroleum ether-EtOAc,
1:1) indicated that the reaction completed, the mixture was
matography (MeOH-H2O-TFA, 6:2:0.024) to give 2 (15 mg,
1
68%) as a white solid: [R]27 23.9 (c 0.5, MeOH); H NMR (300
D
MHz, C5D5N) δ 6.33 (d, J ) 7.8 Hz, 1H), 6.17 (brs, 1H), 5.40 (s,
1H), 5.30 (ABq, J ) 17.3 Hz, 1H), 5.16 (ABq, J ) 16.6 Hz, 1H),
5.13 (d, J ) 4.6 Hz, 1H), 5.00 (d, J ) 7.6 Hz, 1H), 4.65 (m, 2H),
4.49-4.16 (m, 7H), 4.04 (d, J ) 9.0 Hz, 1H), 3.35-3.32 (m, 1H),
3.19-3.16 (m, 1H), 1.27 (s, 6H), 1.08 (s, 3H), 0.95 (s, 3H), 0.90
(s, 3H), 0.87 (s, 3H), 0.79 (s, 3H); 13C NMR (125 MHz, C5D5N)
δ 176.4, 144.1, 122.8, 106.5, 106.2, 95.7, 89.2, 85.8, 79.3, 78.9,
77.5, 74.6, 74.1, 72.4, 71.2, 65.7, 62.3, 55.7, 48.0, 47.0, 46.2, 42.1,
41.7, 39.9, 39.5, 38.6, 36.9, 34.0, 33.1, 32.5, 30.7, 28.3, 28.1, 26.5,
26.2, 23.7, 23.6, 23.4, 18.5, 17.5, 16.9, 15.5; negative-mode ESIMS
(m/z) 955.1 [M - H]+, 937.1 [M - H3+O]; positive-mode ESIMS
(m/z): 979.5 [M + Na]+, 995.4 [M + K]+; Positive-mode HRMS
(MALDI) calcd for C47H72O20Na [M + Na]+ 979.4509, found
979.4536.
3,4-O-Isopropylidene-2-O-(2-azidomethyl)benzoyl-r-L-ara-
binopyranosyl-(1f3)-[benzyl 1,2,4-tri-O-benzoyl-r-D-glucu-
ronopyranoside] (31). To a mixture of 30 (850 mg, 1.43 mmol)
and 4 Å molecular sieves in anhyd CH2Cl2 (30 mL) was added a
solution of the thioglycoside 29 (1.26 g, 2.0 equiv) in CH2Cl2 (5
mL) at 0 °C dropwise, followed by addition of NIS (660 mg, 3
equiv) and AgOTf (75 mg, 0.2 equiv). The mixture was stirred for
1 h at rt and filtrated. The filtrate was diluted with EtOAc, washed
with aqueous 10% Na2S2O3, and brine, respectively, and then dried
over Na2SO4 and concentrated. Chromatography over silica gel
(petroleum ether-EtOAc, 5:1) gave 31 (1.07 g, 81%) as a white
1
foam: [R]26 59.3 (c 1.1, CHCl3); H NMR (300 MHz, CDCl3) δ
D
8.08-7.01 (m, 24H), 6.74 (d, J ) 3.3 Hz, 1H), 5.62 (t, J ) 9.9
Hz, 1H), 5.54 (dd, J ) 9.6, 3.6 Hz, 1H), 5.22 (dd, J ) 7.2, 6.3 Hz,
4984 J. Org. Chem. Vol. 73, No. 13, 2008

Synthesis of BetaVulgaroside III
neutralized with Et3N and concentrated. The residue was purified
by column chromatography on silica gel (petroleum ether-
EtOAc-CH2Cl2, 1:1:1) to give 34 (23 mg, 81%) as a white solid:
Ar for 1 h. A solution of TBSOTf in CH2Cl2 (0.1 equiv) was added
dropwise at 0 °C. After being stirred at rt for 1 h, the mixture was
neutralized with Et3N and then filtered and concentrated. The
residue was purified by column chromatography on silica gel
[R]26 58.0 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3) δ
D
8.06-7.09 (m, 25H), 6.77 (d, J ) 3.6 Hz, 1H), 5.74 (t, J ) 9.6
Hz, 1H), 5.56 (dd, J ) 3.3, 9.6 Hz, 1H), 5.39 (d, J ) 3.9 Hz, 1H),
5.16 (d, J ) 11.7 Hz, 1H), 4.98 (d, J ) 11.7 Hz, 1H), 4.88 (t, J )
3.3 Hz, 1H), 4.73-4.67 (m, 2H), 4.07 (br, 1H), 3.58 (br, 1H), 3.29
(dd, J ) 5.7, 11.1 Hz, 1H), 3.01 (br, 1H); 13C NMR (75 MHz,
CDCl3) δ 166.8, 165.5, 165.0, 164.7, 163.9, 134.0, 133.9, 133.8,
133.4, 133.4, 133.3, 130.1, 130.0, 129.8, 129.7, 129.6, 129.3, 128.7,
128.7, 128.6, 128.6, 128.5, 128.4, 128.3, 128.2, 128.2, 128.0, 97.4,
89.4, 74.9, 72.2, 71.0, 69.9, 69.3, 68.8, 68.2, 65.8, 58.5; HRMS
(MALDI) calcd for C46H40O15Na [M + Na]+ 855.2260, found
855.2266.
Tris-benzyl Ester 35. To a solution of compound 34 (23 mg,
0.028 mmol) in THF-H2O (2 mL:1 mL) at rt was added NaIO4
(60 mg, 10 equiv). The mixture was stirred at 50-60 °C for 2 h,
followed by cooling to 0 °C and the subsequent addition of NaClO2
(27 mg, 10 equiv) and NH2SO3H (27 mg, 10 equiv). The resulting
mixture was stirred at rt for 0.5 h and then diluted with EtOAc.
The organic phase, after being washed with aqueous 10% Na2S2O3
and brine, respectively, was dried over Na2SO4 and concentrated
to give the crude acid as foam. To a solution of the crude acid in
dry DMF (1 mL) were added NaHCO3 (35 mg, 15 equiv) and BnBr
(0.05 mL, 15 equiv). The mixture was heated to 50 °C for 4 h and
was then concentrated and diluted with EtOAc. The organic phase
was washed with water and brine, respectively, and was then dried
over Na2SO4 and concentrated. Chromatography over silica gel
(petroleum ether-EtOAc, 3:1) to give 37 (47 mg, 75%) as a white
1
foam: [R]23 7.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3) δ
D
7.94-7.10 (m, 30H), 5.60-5.55 (m, 2H), 5.42 (t, J ) 5.1 Hz, 1H),
5.35-5.31 (m, 2H), 5.24-5.09 (m, 5H), 5.05-5.94 (m, 4H),
4.78-4.74 (m, 1H), 4.70-4.64 (m, 2H), 4.27 (dd, J ) 12.3, 3.6
Hz, 1H), 4.19-4.01 (m, 4H), 3.79-3.75 (m, 1H), 3.08-3.04 (m,
1H), 2.83-2.77 (m, 1H), 2.06 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H),
1.99 (s, 3H), 1.07 (s, 3H), 0.90 (s, 6H), 0.84 (s, 3H), 0.67 (s, 3H),
0.62 (s, 3H), 0.54 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 175.5,
170.6, 170.1, 169.4, 169.2, 168.9, 166.9, 166.1, 165.2, 164.9, 164.5,
142.8, 135.2, 135.1, 134.7, 133.2, 133.1, 133.1, 129.9, 129.8, 129.7,
129.3, 129.3, 128.6, 128.6, 128.4, 128.4, 128.3, 128.3, 128.2, 128.2,
128.1, 122.9, 103.0, 100.0, 91.5, 90.2, 76.3, 73.6, 73.1, 72.8, 72.7,
72.4, 70.7, 69.9, 68.0, 67.6, 67.2, 66.4, 62.9, 61.5, 55.4, 47.5, 46.8,
45.7, 41.6, 41.0, 39.2, 38.7, 38.4, 36.6, 33.7, 33.0, 32.8, 31.7, 30.6,
27.7, 25.7, 25.6, 23.4, 22.8, 20.7, 20.5, 18.0, 16.9, 16.0, 15.2; HRMS
(MALDI) calcd for C97H110O27Na [M + Na]+ 1729.7127, found
1729.7128.
Betavulgaroside III (1). Compound 37 (18 mg, 0.01 mmol) was
treated with 10% Pd/C (cat.) under 1 atm of H2 in i-PrOH-EtOAc
(1 mL: 2 mL) for 5 h. The mixture was filtered. The filtrate was
concentrated and dissolved in CH2Cl2-MeOH-H2O (1.5 mL:2 mL:
1.5 mL), followed by the addition of LiOH ·H2O (10 mg, 25 equiv).
The resulting mixture was at rt stirred, until TLC
(CH2Cl2-MeOH-H2O, 5:4:1) indicated that the reaction completed.
The mixture was acidified with Dowex 50-X8 (H+) resin to pH )
3.0 and filtered. The filtrates were concentrated and purified by
reversed-phase ODS column chromatography (MeOH-H2O-TFA,
(petroleum ether-EtOAc, 3:1) gave 35 (22 mg, 75%) as a white
1
foam: [R]25 33.3 (c 1.4, CHCl3); H NMR (300 MHz, CDCl3) δ
D
8.06-7.06 (m, 35H), 6.80 (d, J ) 3.0 Hz, 1H), 5.58 (t, J ) 9.0
Hz, 1H), 5.51 (d, J ) 4.2 Hz, 1H), 5.34-4.86 (m, 9H), 4.70 (d, J
) 9.9 Hz, 1H), 4.16 (d, J ) 4.2 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 169.3, 166.9, 166.0, 165.1, 164.9, 164.8, 164.0, 134.9,
134.8, 134.1, 133.8, 133.3, 130.1, 129.9, 129.8, 129.7, 129.5, 128.9,
128.7, 128.6, 128.5,128.4, 128.4, 128.3, 128.2, 128.1, 126.9, 100.2,
89.4, 73.4, 72.7, 71.9, 69.7, 68.0, 67.1, 66.5, 62.4; HRMS (MALDI)
calcd for C60H50O17Na [M + Na]+ 1065.2940, found 1065.2926.
seco-Disaccharide Trichloroacetimidate 36. To a solution of
35 (80 mg, 0.077 mmol) in DMF (3 mL) was added N2H4 ·AcOH
(10 mg, 1.5 equiv). The resulting mixture was stirred at rt overnight
and was then diluted with EtOAc. The organic phase, after being
washed with 1 N HCl, H2O, and brine, respectively, was dried over
Na2SO4 and then concentrated in vacuo. The residue was purified
by column chromatography on silica gel (petroleum ether-EtOAc,
3:1) to give the lactol as a yellow oil. To a solution of the lactol in
dry CH2Cl2 (3 mL) were added excess NCCCl3 and DBU (cat.).
The mixture was stirred at rt for 1 h and was then concentrated.
The residue was purified by flash column chromatography on silica
gel (petroleum ether-EtOAc, 2.5:1) to give 36 (40 mg, 48%; the
6:2:0.024) to afford 1 (8 mg, 85%) as a white solid: [R]23 7.2 (c
D
0.1, MeOH), [lit.2b [R]28D 10.8 (c 0.1, MeOH)]; 1H NMR (400 MHz,
C5D5N) δ 6.33 (d, J ) 8.0 Hz, 1H), 6.31 (brs, 1H), 5.40 (brs, 1H),
5.35 (brs, 1H), 5.31 (brs, 1H), 5.08 (ABq, J ) 16.2 Hz, 1H), 4.99
(d, J ) 7.8 Hz, 1H), 4.65-4.61 (m, 2H), 4.49-4.16 (m, 7H), 4.03
(m, 1H), 3.35 (dd, J ) 11.4, 3.9 Hz, 1H), 3.19 (m, 1H), 1.27 (s,
6H), 1.08 (s, 3H), 0.96 (s, 3H), 0.91 (s, 3H), 0.88 (s, 3H), 0.81 (s,
3H); 13C NMR (125 MHz, C5D5N) δ 176.4, 174.8, 173.9, 172.4,
144.1, 122.8, 106.7, 105.4, 95.7, 89.1, 85.4, 79.3, 78.9, 77.6, 74.8,
74.1, 72.3, 71.1, 65.0, 62.2, 55.7, 47.9, 47.0, 46.2, 42.1, 41.7, 39.9,
39.5, 38.6, 36.9, 34.0, 33.1, 33.0, 32.5, 30.7, 28.2, 28.1, 26.6, 26.1,
23.7, 23.6, 23.4, 18.5, 17.5, 16.9, 15.5; negative-mode ESIMS (m/
z) 955.1 [M - H]+; positive-mode ESIMS (m/z) 979.5 [M + Na]+,
995.4 [M + K]+; positive-mode HRMS (MALDI) calcd for
C47H72O20Na [M + Na]+ 979.4509, found 979.4541.
Acknowledgment. Financial support from the Chinese
Academy of Sciences (KGCX2-SW-213 and KSCX2-YW-R-
23), the National Natural Science Foundation of China
(20621062), and the Committee of Science and Technology of
Shanghai (07DZ22001) is gratefully acknowledged.
1
R-anomer predominates) as a colorless oil: H NMR (300 MHz,
CD3COCD3) δ 9.49 (s, 1H), 8.10-7.22 (m, 30H), 6.87 (d, J ) 3.3
Hz, 1H), 5.70-5.63 (m, 2H), 5.46-5.30 (m, 3H), 5.22-5.00 (m,
6H), 4.83 (d, J ) 9.9 Hz, 1H), 4.47 (ABq, J ) 16.5 Hz, 2H); ESIMS
Supporting Information Available: Experimental proce-
dures, characterization data, and NMR spectra for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
m/z, 1104.2 [M
+
Na]+; HRMS (MALDI) calcd for
C55H46NO16Cl3Na [M + Na]+ 1104.1774, found 1104.1746.
Tris-benzyl Ester 37. A mixture of the glycosyl imidate 36 (40
mg, 0.037 mmol), acceptor 27 (58 mg, 1.5 equiv), and powered 4
Å molecular sieves in anhyd CH2Cl2 (5 mL) was stirred at rt under
JO800669H
J. Org. Chem. Vol. 73, No. 13, 2008 4985