Synthesis of a chlorogenin glycoside library using an orthogonal protecting group strategy

Article abstract of DOI:10.1016/j.carres.2013.04.022

Naturally occurring spirostanol saponins bear a chacotriose, α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→4)] -β-d-glucopyranose residue as the oligosaccharide moiety which is believed to be important for biological activity. Herein the development of a concise, combinatorial method for the synthesis of two series of glycan variants at the 2′ and/or 4′ positions of chacotriose is described and the structure-activity relationships of the glycone part at 3-OH of chlorogenin investigated. These compounds were found to be weakly-cytotoxic toward leukemia cell lines CCRF and HL-20, indicating that the chacotriose moiety is important for anticancer activity.

Full text of DOI:10.1016/j.carres.2013.04.022

Carbohydrate Research 375 (2013) 118–135
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of a chlorogenin glycoside library using an orthogonal
protecting group strategy
Ying-Hsin Wang a, , Hsien-Wei Yeh a, , Hsiao-Wen Wang a, Chia-Chun Yu a, Jih-Hwa Guh a, Der-Zen Liu b,
Pi-Hui Liang a,
⇑
a School of Pharmacy, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei 100, Taiwan
b Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Naturally occurring spirostanol saponins bear a chacotriose, a-L-rhamnopyranosyl-(1?2)-[a-L-rhamno-
pyranosyl-(1?4)]-b-D-glucopyranose residue as the oligosaccharide moiety which is believed to be
Received 21 February 2013
Received in revised form 12 April 2013
Accepted 13 April 2013
important for biological activity. Herein the development of a concise, combinatorial method for the syn-
thesis of two series of glycan variants at the 20 and/or 40 positions of chacotriose is described and the
structure–activity relationships of the glycone part at 3-OH of chlorogenin investigated. These com-
pounds were found to be weakly-cytotoxic toward leukemia cell lines CCRF and HL-20, indicating that
the chacotriose moiety is important for anticancer activity.
Available online 28 April 2013
Keywords:
Chacotriose
Glycoside
Cytotoxicity
Dioscin
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
bohydrate domain of natural products may lead to a better under-
standing of the recognition process and has potential to identify
Steroidal saponins are steroidal glycosides and can be divided
into two major groups, spirostanosides and furostanosides. Spi-
rostanosides bear one sugar chain, generally at the C-3 position,
and furostanosides bear two sugar chains, one at the C-3 and the
other at the C-26 positions.1 Dioscin (1, Scheme 1), which bears a
new therapeutics. Consequently, the development of practical
methods to create a library of glycosides might help to achieve
these goals. To date, two general strategies for the construction
of saponins have been disclosed: a convergent approach (Route
1, Scheme 2), in which the aglycon is directly glycosylated with a
prefabricated sugar donor;12–15 and a linear synthesis (Route 2,
Scheme 2), in which the aglycon is glycosylated with a monosac-
charide, and subsequently elongated via a series of protecting
group manipulations.16–23 Both strategies have been applied to
the synthesis of dioscin derivatives,12–23 but each has limitations.
The first is efficient, but is limited to a specific fabricated sugar do-
nor, and glycosylation with an oligosaccharide donor which con-
tains a (1?2)-linkage at the reducing end where no neighboring-
group participation can be exploited, the glycosylation would be
low yielding due to the low selectivity of 1,2-tans-glycosylation.
In fact, such type of oligosaccharides is common in natural sapo-
nins.24 The second is inefficient, due to the laborious protecting
group manipulations required between each glycosylation step.
Orthogonal protecting group strategies25,26 have been developed
to alleviate these problems, at least in part.
chacotriosyl
(a
-L
-rhamnopyranosyl-(1?2)-[
a-L-rhamnopyrano-
syl-(1?4)]-b-
D-glucopyranosyl) moiety at the 3-OH of diosgenin,
is one of the most commonly occurring spirostanosides, occurring
widely in plants. Amongst the wide range of bioactivities that spi-
rostannosides exhibit, hemolytic and cytotoxic activities are the
two most commonly observed activities, and recent studies have
shown that dioscin can induce apoptosis within tumor cells.2–4
A
few structure–activity relationship (SAR) studies of dioscin have
been documented5–7 indicating that subtle modification of the gly-
can portion is well tolerated. Recently, chlorogenin 3-O-b-chacotri-
oside (2) and its derivatives were reported to be potent entry
inhibitors of the H5N1 influenza virus.8,9 The SAR study indicated
that the sugar part is important for bioactivity.
Many of these bioactive compounds contain sugar units, which
are often required for function in vivo. Glycosylation of natural
products may affect solubility, stability, or molecular recognition
associated with the biological target.10,11 Modification of the car-
Most of the aforementioned SAR studies maintained a rham-
nose moiety at the 20- and 40-positions of the chacotriose moiety
(e.g., 1 & 2, Scheme 1) and SAR studies of analogs bearing alterna-
tive saccharides at these positions are yet to be conducted. We
have developed a concise and combinatorial strategy to construct
the saccharide library 3 of chlorogenin. Compound 4 was identified
⇑
Corresponding author. Fax: +886 2322 5095.
E-mail address: phliang@ntu.edu.tw (P.-H. Liang).
These authors contributed equally to this work.
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.04.022

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
119
O
O
O
O
H
H
OH
OH
HO
HO
HO
O
H
O
H
HO
HO
O
HO
O
HO
O
O
O
O
O
O
OH
HO
O
O
HO
HO
HO
HO
HO
1
2
HO
O
O
O
O
OH
O
OBn
O
O
R2
LevO
BnO
O
HO
O
O
OH
ONPAc
OAc
R1
3
4
R1 and R2 = H, monosaccharide, or disaccharide
O
O
O
O
HO
HO
OAc
5
diosgenin
Scheme 1. Structure of 1 and 2 and a possible approach for modification of chlorogenin to give a library of 3 which can be retrosynthesized from diosgenin.
Route 1
a, b
O
X
O
O
O
O
O
O
O
HO
X
a, b
a, b
O
X
O
Route 2
O
X = leaving groups
Scheme 2. Two synthetic strategies toward saponins. Route 1 is a convergent approach. Route 2 is the linear approach. (a) Glycosylation step; (b) Protective group
manupulations.
as the key intermediate (Scheme 1), in which 2-nitrophenylace-
tyl27 and levulinoyl groups were chosen to protect the 2- and 4-
positions of glucose, respectively. Orthogonal deprotection of core
4 followed by combinatorial glycosyltion with various glycoyl do-
nors, yielded a library of chlorogenin (3) analogs.
To synthesize the core structure 4, compound 7,28 was pre-
pared from 1,2,5,6-diisopropylidene- -glucose (Scheme 4), treat-
D
ment with p-thiotoluene and BF3ꢀOEt2 in CH2Cl2 to give
thioglycoside 8. Compound 8 was subjected to ester hydrolysis
by cat. NaOMe in MeOH to give 9, and then the 4,6-diol group
was protected to give the benzylidene acetal 10 by treatment with
benzaldehyde dimethyl acetal in acetonitrile (ACN), in the pres-
ence of camphorsulfonic acid (CSA). 2-Nitrophenylacetyl (NPAc)
group was chosen for installation at 2-OH of compound 10, as it
could selectively be removed through zinc-catalyzed reduction27
when desired and can also help in imparting b-selectivity during
the glycosylation through neighboring group participation. The
2-OH of 10 was thus protected with NPAc, installed by treating
with NPAcOH in the presence of dicyclohexylcarbodiimide (DCC)
2. Results and discussion
The synthetic route to glycosyl acceptor 5 is depicted in
Scheme 3. After the 3-OH of diosgenin was protected with a benzyl
group, hydroboration–oxidation of the 5,6-double bond introduced
6a
-OH, to give compound 6.21 The newly formed alcohol at 6-posi-
tion was acetylated, and the 3-OBn was removed by Pd/C-cata-
lyzed hydrogenolysis to give glycosyl acceptor 5 for later use.

120
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
O
O
O
O
b
O
a
O
BnO
HO
HO
OH
OAc
Diosgenin
5
6
Scheme 3. Reagents and conditions: (a) (i) NaH, BnCl/THF, DMF, 0–60 °C, 15 h; (ii) BH3/THF, 0 °C to rt, 12 h; (iii) 10 N NaOH, H2O2, rt, 2 h, 32% three steps; (b) (i) Ac2O/
pyridine, DMAP, 0 °C to rt; (ii) H2, Pd/C, rt, 12 h, 92% two steps.
OH
O
OAc
O
OAc
O
Ph
O
a
b
c
d
O
O
AcO
BnO
AcO
BnO
HO
STol
h, i
STol
BnO
STol
OAc
BnO
OH
OH
OAc
OAc
9
10
OBn
7
8
OBn
OBn
O
g
Ph
O
e
f
O
LevO
O
O
LevO
BnO
4
O
HO
BnO
OH
BnO
STol
STol
ONPAc
STol
BnO
ONPAc
ONPAc
ONPAc
13
14
11
12
Scheme 4. Reagents and conditions: (a) p-toluenethiol, BF3ꢀOEt2/CH2Cl2, 0 °C to rt, 8 h, 73%; (b) NaOMe/MeOH, rt, 12 h, 87%; (c) benzaldehyde dimethyl acetal, CSA/ACN, rt,
4 h, 76%; (d) (2-nitro)phenylacetic acid, DCC, DMAP/CH2Cl2, rt, 12 h, 74%; (e) Et3SiH, BF3ꢀOEt2/CH2Cl2, 0 °C to rt, 4 h, 99%; (f) LevOH, EDC, DMAP/CH2Cl2, rt, 12 h, 94%; (g) NBS,
H2O/acetone, ꢁ25 °C, 1 h, 98%; (h) CCl3CN, DBU/CH2Cl2, rt, 2 h, 81%; (i) 5, TMSOTf/CH2Cl2, 3 Å MS, ꢁ25 °C, 0.5 h, 60%.
to afford compound 11. The 4,6-benzylidene group of 11 was
reductively opened29 using Et3SiH and BF3ꢀOEt2 in DCM to give
60-OBn compound 12, and then the 4-OH of 12 was protected with
a levulinoyl group to give 13. Subsequently, compound 13 was
subjected to hydrolysis with N-bromosuccinimide (NBS) in ace-
tone and water, followed by treatment with trichloroacetonitrile
and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give the fully
protected glycosyl trichloroacetimidate 14. Straightforward glyco-
sylation of chlorgenin with 14 using TMSOTf in DCM having 3 Å
MS afforded the core structure 3-b-O-glucopyranosides 4 in 60%
yield and with complete selectivity for the beta diastereomers,
as moved by NMR.
26 with compound 23, was then converted to glycosyl trichloro-
acetimidate 24 by successively treating with NBS in aqueous ace-
tone and CCl3CN and DBU.
With the core 4 as a glycosyl acceptor and 10 glycosyl donors
15–24 in hand, orthogonal removal of the 40-O-levulinoyl group
using hydrazine acetate and of the 20-O-2-nitrophenylacetyl group
using Zn/NH4Cl afforded compounds 28 and 29, respectively
(Scheme 7). Compounds 28 and 29 were then glycosylated with
various glycosyl donors 15–24 in CH2Cl2 at ꢁ25 °C using TMSOTf
as a promoter to give compounds 30–39 with b(1?2) linkage
and 40–49 with b(1?4) linkage, respectively. In addition, the 30-
OLev group of compound 48 was removed using hydrazine and
the product glycosylated with glycosyl trichloroacetimidates 23
and 24 to afford 51 and 52, respectively (Scheme 8). Finally, com-
pounds 4, 30–38, 40–48, and 51 were subjected to hydrolysis using
LiOH in THF/MeOH followed by Pd-catalyzed hydrogenolysis to
give desired products 53–62 and 2, 64–72. Compounds 39, 49,
and 52 required additional hydrolysis of the acetonide by acetic
acid, followed by global deprotection methods to afford products
63, 73, and 74 (Scheme 9).
To expand the saponin library, nine sugars (
cose, -xylose, -xylose, -mannose, -glucose,
tose, and
L
-arabinose,
L
-fu-
L
D
D
D
D-galactose, D
-lac-
L
-rhamnose) were selected for combinatorial
glycosylation at the 20 and 40 positions of 4. These were elaborated
to the corresponding series of glycosyl trichloroacetimidate donors
15–23 according to the general procedure depicted in Scheme 5.
Compounds bearing a di-(a-L-rhamnopyranosyl) moiety at-
tached at 20- or 40-position of 3-glucosyl-diosgenin, such as dicho-
min, was reported to exhibit various biological activities.30 To
further evaluate the role of rhamnose in the biological activity,
The in vitro activities of the chlorogenin derivatives (2, 53–74)
against the leukemia cell CCRF were evaluated using the tetrazo-
lium dye (MTT) assay.31 Dioscin, as a positive control, showed an
bis(a-L-rhamnopyranosyl donor 24 was also synthesized
(Scheme 6). After protection of 25 by 2,2-dimethoxyl propane
(2,2-DMP) to give 2,3-O-acetonide 26, and after glycosylation of
IC50 of 2.5
played significantly reduced activities. Compounds bearing
syl-, -galactosyl-, or -lactosyl, -rhamnosyl-, and 4-O-(
rhamnosyl)-
-rhamnosyl at the 20OH of 3-O-b-glycosyl-chlorog-
enin (55, 60, 61, 62, 63) displayed weak anti-tumor activities,
inhibiting 20–40% cell growth at a concentration of 10 M; how-
ever, their GI50 was all over 30 M. Similar results were seen in as-
says against leukemia cell line HL-60 and human prostate
carcinoma PC-3, leading us to conclude that chacotriosyl glycoside
moiety is essential for cytotoxicity. The ability of these compounds
to block the entry of the H5N1 influenza virus was also evaluated;
no inhibitory activity was found. The inconsistent nature of our re-
sults to the literature might be due to the differing assay condi-
tions; this is currently being investigated, and results will be
reported in due course.
l
M, but the chlorogenin derivatives synthesized dis-
L
-fuco-
D
D
L
a-L-
a
-L
O
O
O
BzO
STol
BzO
O
HO
l
l
O
15
20
: D-Glucose
: L-Arabinose
BzO
CCl3
NH
16: L-Fucose
17: L-Xylose
18: D-Xylose
19: D-Mannose
21: D-Galactose
22: D-Lactose
23: L-Rhamnose
15-23
Scheme 5. General preparation of glycosyl trichloroacetimidate donors (a) BzCl,
DMAP/pyridine, 0 °C to rt, 5 h; (b) p-toluenethiol, BF3ꢀOEt2/CH2Cl2, 0 °C to rt, 8 h; (c)
NBS, H2O/acetone, ꢁ25 °C, 1 h, 98%; (d) CCl3CN, DBU/CH2Cl2, rt, 2 h, 81%.

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
121
NH
STol
STol
O
CCl3
STol
O
b
c, d
O
a
O
O
O
HO
O
OH
O
O
O
BzO
O
O
OH
O
O
O
OH
BzO
BzO
OBz
27
BzO
OBz
25
26
24
Scheme 6. Reagents and conditions: (a) 2,2-DMP, acetone, CSA, rt, 15 h, 72%; (b) 23, TMSOTf/CH2Cl2, 3 Å MS, ꢁ25 °C, 0.5 h, 68%; (c) NBS, H2O/acetone, -25 °C, 1 h, 98%; (d)
CCl3CN, DBU/CH2Cl2, rt, 2 h, 81%.
OBn
O
OBn
O
O
O
c
a
b
O
LevO
BnO
LevO
BnO
OAc
OAc
OR
OH
O
28
30-39
OBn
O
O
LevO
BnO
OAc
ONPAc
OBn
O
c
4
OBn
O
O
RO
O
HO
BnO
OAc
BnO
OAc
ONPAc
40-49
ONPAc
29
OBz
O
OBz
O
BzO
(82%, 89%)
(82%, 45%)
(82%, 55%)
(49%, 57%)
(34%, 62%)
30, 40: R=
35, 45: R=
BzO
BzO
BzO
OBz
OBz
O
OBz
O
31, 41
32, 42
: R=
: R=
(35%, 34%)
OBz
36, 46
: R=
BzO
OBz
BzO
BzO
OBz
OBz
O
OBz
O
BzO
O
O
(48%, 53%)
OBz
37, 47: R=
38, 48: R=
BzO
BzO
BzO
OBz
OBz
O
BzO
BzO
33, 43: R=
O
(49%, 95%)
BzO
OBz
BzO
OBz
O
BzO
OBz
O
O
34, 44
: R=
39, 49
: R=
BzO
BzO
O
(61%, 70%)
(48%, 46%)
O
O
BzO
BzO
OBz
Scheme 7. Reagents and conditions: (a) Zn, NH4Cl/CH2Cl2, MeOH, rt, 12 h, 81%; (b) hydrazine acetate/CH2Cl2, MeOH, rt, 8 h, 70%; (c) 15–24, TMSOTf/CH2Cl2, 3 Å MS, ꢁ25 °C,
0.5 h.
3. Conclusion
4. Experimental
An efficient method for the construction of a glycosyl library of
chlorogenin 3b-O-glucosides has been developed. Both the 20-OH
and 40-OH groups of chlorogenin 3b-O-glucoside were glycosylated
with 10 different glycoside donors to afford di-, tri-, and tetra-sac-
charides corresponding to chlorogenin glycosides. All these com-
pounds were subjected to anti-cytotoxic, and anti-influenza entry
assays, but none showed potent activity, suggesting that the un-
ique 20,40-di-O-rhamnosyl moiety of dioscin is essential for activity.
It is thought that our method, using orthogonal approach to effi-
ciently construct more than 20 derivatives of dioscin is useful to
investigate the SAR of bioactive glucose-conjugated compounds.
4.1. General methods
Reactions were monitored by thin-layer chromatography
(Merck, silica gel 60F-254) using p-anisaldehyde or cerium molyb-
date as the stain reagent. Silica gel used for flash column chroma-
tography was Mallinckrodt type 60 (230–400 mesh). Unless
otherwise noted, reagents and materials were obtained from com-
mercial sources and used as provided without further purification.
1H and 13C NMR spectra were recorded on a Bruker AV-400 or AVI-
II-600-Cry spectrometer and referenced to residual solvent peaks
(CDCl3: 1H d = 7.24, 13C d = 77.0; [D4] MeOH:1H d = 3.30, 13C

122
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
O
O
OBn
O
OBn
O
OBn
O
O
a
b
RO
BnO
O
OAc
HO
O
LevO
BnO
O
BnO
OAc
OAc
O
O
O
BzO
O
O
BzO
BzO
OBz
BzO
BzO
OBz
BzO
OBz
O
OBz
48
51
52
(83%)
: R=
BzO
50
BzO
O
O
(61%)
: R=
O
O
O
BzO
BzO
OBz
Scheme 8. Reagents and conditions: (a) hydrazine acetate/CH2Cl2, MeOH, rt, 8 h, 78%; (b) 23 or 24 TMSOTf/CH2Cl2, 3 Å MS, ꢁ25 °C, 0.5 h.
O
a, b
O
4, 30-38, 40-48, 51
39, 49, 52
OH
O
O
R2O
HO
c, a, b
OH
OR1
53
: R1 = H, R2 = H (58%)
64: R1 = H, R2 = β-L-arabinose (43%)
65
66
67
68
54: R1 = β-L-arabinose, R2 = H (41%)
55: R1 = β-L-fucose, R2 = H (50%)
: R1 = H, R2 = β-L-fucose (65%)
: R1 = H, R2 = β-L-xylose (60%)
: R1 = H, R2 = β-D-xylose (40%)
: R1 = H, R2 = α-D-mannose (45%)
56
57
58
,
: R1 = β-L-xylose R2 = H (60%)
: R1 = β-D-xylose, R2 = H (45%)
α D
- -mannose, R2 = H (88%)
69
70
: R1
=
: R1 = H, R2 = β-D-glucose (45%)
: R1 = H, R2 = β-D-galactose (42%)
59: R1 = β-D-glucose, R2 = H (63%)
60: R1 = β-D-galactose, R2 = H (49%)
61: R1 = β-D-lactose, R2 = H (42%)
71
72
: R1 = H, R2 = β-D-lactose (32%)
: R1 = H, R2 = α-L-rhamnose (62%)
: α-L-rhamnose, R2 = α-L-rhamnose (73%)
: R1 = H, R2 = α-4-O-(L-rhamnose)-L-
62
2
: R1 = α-L-rhamnose, R2 = H (70%)
73
63
: R1 = α-4-O-(L-rhamnose)-L-rhamnose,
rhamnose (41%)
R
2 = H (42%)
74: R1 = R1 = α-L-rhamnose,
R2 = α-4-O-(L-rhamnose)-L-rhamnose (31%)
Scheme 9. Reagents and conditions: (a) LiOH/THF/MeOH (3:1), rt, 12 h; (b) H2, Pd/C, rt, 12 h; (c) 80% AcOH, 60 °C, 24 h.
d = 49). Exact mass measurements were performed on VG platform
5 mg/mL and filtered. From the stock solution, 10
l
L per 100 lL
electrospray ESI/MS or BioTOF II (Taiwan).
of medium was added to each well, and plates were gently shaken
and incubated at 37 °C for 1 h. After the loading of MTT, the med-
4.2. Cell culture and cytotoxic assay
ium was replaced with 100 lL acidified b-isopropanol and left for
5–10 min at rt for color development. The plate was read by en-
zyme-linked immunosorbent assay reader (570 nm) to get the
absorbance density values.
Leukemia cell line CCRF, HL-20, and human prostate carcinoma
cell line PC-3 were obtained from the American Type Culture Col-
lection (Rockville, MD). Cells were cultured in RPMI 1640 medium
with 10% FBS (v/v) and penicillin (100 U/mL)/streptomycin
4.3. Synthesis and characterization of compounds
(100 lg/mL). Cultures were maintained in a humidified incubator
at 37 °C in 5% CO2/95% air. Cells were incubated in the absence
or presence of the compounds for the indicated concentrations
and times, and then the mitochondrial MTT reduction activity
was assessed. MTT was dissolved in PBS at a concentration of
4.3.1. 3b-O-Benzylchlorogenin (6)
NaH (5.8 g, 144.7 mmol) was slowly added to a solution of dios-
genin (30 g, 72.3 mmol) in THF/DMF (1:1, 500 mL) at 0 °C, with
stirring. After 10 min, benzyl chloride (16.7 mL, 144.7 mmol) was

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
123
added, and the solution was maintained at 60 °C for 15 h. The reac-
tion mixture was diluted with methanol and CH2Cl2 and was
washed subsequently with water and satd NaHCO3. The organic
layer was dried over MgSO4, filtered, and concentrated to obtain
the crude products, which were purified by recrystallization from
CHCl3 to afford 3b-O-benzyldiosgenin. A solution of 1.0 N BH3 in
THF (89.1 mL, 89.1 mmol) was added slowly to a solution of 3b-
O-benzyldiosgenin (15.0 g, 29.7 mmol) in dry THF (200 mL) under
nitrogen at 0 °C. The mixture was warmed to rt and stirred over-
night. 10 N NaOH (18.5 mL, 185 mmol) was added over 30 min at
0 °C, followed by addition of 30% H2O2 (18.2 mL, 13 mmol), and
vigorous stirring was continued at rt for 2 h. The mixture was di-
luted with CH2Cl2 and washed with 1.0 N HCl, satd NaHCO3, and
brine, and dried over MgSO4, filtered, and concentrated in vacuum.
The residue was column chromatographed on silica gel EtOAc/hex-
ane, 1:2) to give 6 (12 g, 32%) as white solid: mp 186–190 °C; 1H
J = 8.1 Hz, 2H, H-Ar), 7.27–7.25 (m, 3H, H-Ar), 7.19 (d, J = 8.1 Hz,
2H, H-Ar), 7.08 (d, J = 8.1 Hz, 2H, H-Ar), 5.03 (t, J = 9.6 Hz, 1H, H-
4), 5.00 (t, J = 9.7 Hz, 1H, H-2), 4.57 (dd, J = 11.6, 15.5 Hz, 2H, CH2
of Bn), 4.55 (d, J = 10.2 Hz, 1H, H-1), 4.13–4.11 (m, 2H, H-6a, H-
6b), 3.69 (t, J = 9.2 Hz, 1H, H-3), 3.58–3.56 (m, 1H, H-5), 2.32 (s,
3H, CH3 of STol), 2.05 (s, 3H, CH3 of Ac), 2.02 (s, 3H, CH3 of Ac),
1.94 (s, 3H, CH3 of Ac); 13C NMR (CDCl3, 100 MHz,) d 170.5,
169.26, 169.1 (OC@O), 138.3, 137.6, 133.1, 129.5, 128.4, 128.3,
127.7, 127.6, 86.3 (C-1), 81.4, 75.9, 74.1, 71.2, 69.5, 62.4, 21.0,
20.8, 20.6, 20.6; HRMS (ESI) calcd for C26H30NaO8S [M+Na]+:
525.1559, found: 525.1552.
4.3.4. p-Tolyl 3-O-benzyl-1-thio-b-D-glucopyranoside (9)
A catalytic amount of NaOMe (260 mg, 4.77 mmol) was added
to a solution of 8 (54.0 g, 107 mmol) in dry methanol (450 mL).
After stirring overnight, the mixture was neutralized with amber-
lite-H+ resin. The resin was then filtered off and the filtrate was
concentrated and then dried in vacuo to obtain 9 (35.0 g, 87%) as
NMR (CDCl3, 400 MHz)
d 7.25–7.14 (m, 5H, H-Ar), 4.50 (d,
J = 11.7 Hz, 1H, CH2 of Bn), 4.43 (d, J = 12.0 Hz, 1H, CH2 of Bn),
4.30 (dd, J = 7.5, 15.0 Hz, 1H, H-16), 3.39–3.18 (m, 4H, H-6, H-3,
H-26a, H-26b), 2.27 (d, J = 12.3 Hz, 1H, OH), 1.89–1.88 (m, 2H),
1.79–1.78 (m, 3H), 1.70–1.48 (m, 9H), 1.39–1.38 (m, 3H), 1.22–
0.98 (m, 5H), 0.87–0.86 (m, 5H), 0.73 (s, 3H, H-19), 0.70 (d,
J = 6.2 Hz, 3H, H-27), 0.67 (s, 3H, H-18), 0.57–0.56 (m, 1H); 13C
NMR (CDCl3, 100 MHz) d 138.9, 128.2, 127.4, 127.2, 109.1 (C-22),
80.6 (C-16), 77.84 (C-6), 69.83 (CH2 of Bn), 69.1 (C-3), 66.7 (C-
26), 62.0, 55.8, 53.7, 51.4, 41.7, 41.5, 40.4, 39.7, 37.1, 36.5, 33.7,
31.6, 31.2, 30.1, 28.69, 28.68, 28.0, 20.8, 17.0 (C-27), 16.3 (C-18),
14.4 (C-21), 13.3 (C-19); HRMS (ESI) calcd for C34H51O4 [M+H]+:
523.7663, found: 523.7662.
a white solid: mp 143 °C; ½a D25
ꢂ
ꢁ82.1 (c 0.056, CH2Cl2); 1H NMR
(CDCl3, 400 MHz) d 7.29 (d, J = 8.1 Hz, 2H, H-Ar), 7.25–7.14 (m,
5H, H-Ar), 7.01 (d, J = 7.9 Hz, 2H, H-Ar), 4.89 (d, J = 11.7 Hz, 1H,
CH2 of Bn), 4.63 (d, J = 11.7 Hz, 1H, CH2 of Bn), 4.37 (d, J = 9.1 Hz,
1H, H-1), 3.78 (d, J = 11.7 Hz, 1H, H-4), 3.64 (d, J = 11.3 Hz, 1H, H-
2), 3.40 (t, J = 9.1 Hz, 1H, H-3), 3.33–3.3.25 (m, 3H, H-5, H-6a, H-
6b), 2.23 (s, 3H, CH3 of STol); 13C NMR (CDCl3, 100 MHz,) d 138.7,
138.3, 133.4, 129.9, 128.6, 128.0, 127.3, 88.7 (C-1), 85.0, 79.3,
74.8, 72.5, 70.0, 62.7, 21.1; HRMS (ESI) calcd for C20H24NaO5S
[M+Na]+: 399.1242, found: 399.1240.
4.3.5. p-Tolyl 3-O-benzyl-4,6-O-benzylidene-1-thio-b-D-
4.3.2. 6a-O-Acetylchlorogenin (5)
glucopyranoside (10)
Acetic anhydride (3.4 mL, 34.4 mmol) and DMAP (28 mg,
0.23 mmol) were added to a solution of 6 (12.0 g, 23.0 mmol) in
pyridine (150 mL) at 0 °C. The mixture was stirred at rt for 2 h,
and then concentrated in vacuo. The residue was diluted with
CH2Cl2 and then extracted with 1.0 N HCl and 1.0 N NaOH for three
times. The organic layer was dried over MgSO4, filtered, and con-
centrated. A suspension of the crude products and Pd–C (1.5 g,
10%) in CH2Cl2/ethanol (1:4, 150 mL) was stirred under H2 for
12 h, filtered, and concentrated. The residue was purified by col-
umn chromatography on silica gel (EtOAc/n-hexane, 1:2) to afford
5 (10.0 g, 92%) as a off-white solid: mp 230 °C; 1H NMR (CDCl3,
400 MHz) d 4.68–4.67 (m, 1H, H-6), 4.35 (dd, J = 14.8, 17.2 Hz,
1H, H-16), 3.52–3.51 (m, 1H, H-3), 3.45–3.44 (m, 1H, H-26a),
3.34 (t, J = 10.8 Hz, 1H, H-26b), 2.01 (s, 3H, CH3 of Ac), 1.94–1.93
(m, 2H), 1.82–1.81 (m, 3H), 1.74–1.37 (m, 13H), 1.28–0.97 (m,
6H), 0.93 (d, J = 7.0 Hz, 3H, H-21), 0.86 (s, 3H, H-19), 0.76 (d,
J = 6.4 Hz, 3H, H-27), 0.73 (s, 3H, H-18), 0.68–0.67 (m, 1H); 13C
NMR (CDCl3, 100 MHz) d 170.7 (OC@O), 109.2 (C-22), 80.6 (C-16),
72.1 (C-6), 70.9 (C-3), 66.8 (C-26), 62.0, 55.9, 53.7, 48.7, 41.6,
40.5, 39.8, 37.7, 37.1, 36.6, 33.7, 32.2, 31.6, 31.3, 31.1, 30.2, 28.7,
21.2 (CH3 of Ac), 20.9, 17.1 (C-27), 16.4 (C-18), 14.4 (C-21), 13.3
(C-19); HRMS (ESI) calcd for C29H47O5 [M+H]+: 475.3423, found:
475.3429.
CSA (2.2 g, 9.3 mmol) was added to a solution of 9 (35.0 g,
93.1 mmol) and benzaldehyde dimethyl acetal (42 mL, 288 mmol)
in dry acetonitrile (350 mL). The mixture was stirred under nitro-
gen for 4 h at rt. Then, the mixture was quenched with triethyl-
amine until it had a pH value of 7, and concentrated in vacuo.
The residue was purified by column chromatography on silica gel
(EtOAc-n-hexane, 1:7) to afford 10 (33.0 g, 71 .1 mmol, 76%) as a
white solid: mp 110 °C; ½a D25
ꢂ
ꢁ31.9 (c 0.09, CH2Cl2); 1H NMR
(CDCl3, 400 MHz) d 7.98 (d, J = 7.9 Hz, 1H, H-Ar), 7.50–7.12 (m,
11H, H-Ar), 6.99 (d, J = 8.0 Hz, 2H, H-Ar), 5.43 (s, 1H, CHPh), 4.82
(d, J = 11.6 Hz, 1H, CH2 of Bn), 4.67 (d, J = 11.6 Hz, 1H, CH2 of Bn),
4.44 (t, J = 9.8 Hz, 1H, H-1), 4.25 (dd, J = 4.9, 10.6 Hz, 1H, H-6a),
3.65 (t, J = 10.2 Hz, 1H, H-4), 3.55 (dd, J = 8.6, 17.2 Hz, 1H, H-3),
3.50 (t, J = 9.2 Hz, 1H, H-2), 3.36–3.34 (m, 2H, H-6b, H-5), 2.21 (s,
3H, CH3 of STol); 13C NMR (CDCl3, 100 MHz,) d 138.7, 138.1,
137.1, 133.8, 133.6, 130.1, 129.78, 129.75, 129.3, 128.9, 128.5,
128.4, 128.4, 128.2, 128.1, 127.8, 127.1, 125.9, 101.2 (CHPh), 88.5
(C-1), 81.6, 81.1, 74.7, 72.0, 70.6, 68.6, 21.1 (CH3 of STol); HRMS
(ESI) calcd for C27H28NaO5S [M+Na]+: 487.1555, found: 487.1549.
4.3.6. p-Tolyl 3-O-benzyl-4,6-O-benzylidene-2-O-(2-
nitro)phenylacetyl-1-thio-b-D-glucopyranoside (11)
(2-Nitro)phenylacetic acid (25.7 g, 142 mmol), DCC (15.4 g,
74.6 mmol), and DMAP (2.2 g, 28 mmol) were added to a solution
of 10 (33.0 g, 71.1 mmol) in dry CH2Cl2 (350 mL) under nitrogen,
and stirred overnight at rt. The precipitation formed in this reac-
tion mixture was removed by filtration and the residue was
washed with CH2Cl2. The filtrate was concentrated in vacuo and
then purified by column chromatography on silica gel (toluene/
acetone, 95:5) to afford 11 (33.0 g, 74%) as a white solid: mp
4.3.3. p-Tolyl 2,4,6-tri-O-acetyl-3-O-benzyl-1-thio-D-
glucopyranoside (8)
The mixture of 728 (65.0 g, 148 mmol) was dissolved in dry
CH2Cl2 (400 mL) and cooled to 0 °C in an ice bath. p-Toluenethiol
(27.6 g, 222.4 mmol) and BF3ꢀOEt2 (37.6 mL, 296.5 mmol) were
added slowly under N2 at 0 °C. The reaction mixture was warmed
to 25 °C over 8 h. The reaction mixture was diluted with CH2Cl2
and extracted three times with 1.0 N NaOH, water, and brine.
The organic layers were separated, dried over MgSO4, filtered, con-
centrated, and recrystallized from ethanol to give 8 (54.0 g, 73%) as
a white solid: mp 142 °C; 1H NMR (CDCl3, 400 MHz) d 7.37 (d,
164 °C; ½a 2D5
ꢂ
ꢁ31.9 (c 0.1, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d
7.93 (d, J = 8.0 Hz, 1H, H-Ar), 7.39 (t, J = 8.0 Hz, 1H, H-Ar), 7.32
(m, 3H, H-Ar), 7.27–7.12 (m, 11H, H-Ar), 6.98 (d, J = 8.0 Hz, 2H,
H-Ar), 5.42 (s, 1H, CHPh), 4.87 (t, J = 9.0 Hz, 1H, H-2), 4.70 (d,
J = 11.8 Hz, 1H, CH2 of Bn), 4.49 (d, J = 11.8 Hz, 1H, CH2 of Bn),

124
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
4.48 (d, J = 10.0 Hz, 1H, H-1), 4.24 (dd, J = 5.0, 10.5 Hz, 1H, H-6a0),
3.94 (d, J = 16.6 Hz, 1H, CH2 of NPAc), 3.87 (d, J = 16.6 Hz, 1H, CH2
of NPAc), 3.64–3.62 (m, 2H, H-6b0, H-3), 3.56 (d, J = 9.4 Hz, 1H, H-
4), 3.35–3.33 (m, 1H, H-5), 2.21 (s, 3H, CH3 of STol); 13C NMR
(CDCl3, 150 MHz,) d 168.2 (OC@O), 138.5, 138.1, 137.0, 134.4,
133.6, 133.2, 133.0, 129.6, 128.9–127.5, 125.9, 125.1, 101.1 (CHPh),
86.7 (C-1), 81.1 (C-4), 80.0 (C-3), 74.3 (CH2 of Bn), 72.2 (C-2), 70.40
(C-5), 68.4 (C-6), 39.2 (CH2 of NPAc), 21.1 (CH3 of STol). HRMS (ESI)
calcd for C35H33NO8SNa [M+Na]+: 650.1819, found: 650.1799.
ꢁ25 °C. The reaction mixture was continuously stirred at ꢁ25 °C
for 1 h. It was quenched by satd NaHCO3 and 1.0 N Na2S2O3 until
the color of the mixture changed from yellow to white. The solu-
tion was diluted with CH2Cl2 and washed sequentially with water
and brine, dried over MgSO4, filtered, and concentrated. The crude
mixture was purified by column chromatography (EtOAc/n-hex-
ane, 1:2) to afford 14 (30 g, 98%) as a off-white solid: mp 108 °C;
½
a 2D5 +48.1 (c 0.2, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.04 (d,
ꢂ
J = 8.1 Hz, 1H, Ar-H), 7.50 (t, J = 7.5 Hz, 1H, Ar-H), 7.41–7.24 (m,
12H, H-Ar), 5.46–5.44 (m, 1H, H-1), 5.09 (t, J = 9.7 Hz, 1H, H-4),
4.90 (dd, J = 3.4, 10.0 Hz, 1H, H-2), 4.62 (d, J = 11.9 Hz, 1H, CH2 of
Bn), 4.55 (d, J = 11.9 Hz, 1H, CH2 of Bn), 4.51 (s, 2H, CH2 of Bn),
4.18 (m, 1H, H-5), 4.08 (t, J = 9.6 Hz, 1H, H-3), 4.02 (d, J = 17.1 Hz,
1H, CH2 of NPAc), 3.94 (d, J = 17.1 Hz, 1H, CH of NPAc), 3.53–3.52
(m, 2H, H-6a0, H-6b0), 2.60–2.55 (m, 2H, CH2 of Lev), 2.39–2.30
(m, 2H, CH2 of Lev), 2.10 (s, 3H, CH3 of Lev); 13C NMR (CDCl3,
150 MHz) d 206.3 (C@O), 171.1, 169.0 (OC@O), 148.0, 138.2,
137.4, 133.4, 132.9, 129.0, 128.3, 127.9–127.0, 124.8, 89.5 (C-1),
76.5 (C-3), 74.1 (CH2 of Bn), 74.0 (C-2), 73.0 (CH2 of Bn), 70.4 (C-
4), 68.6 (C-6), 68.0 (C-5), 39.2 (CH2 of NPAc), 37.3 (CH2 of Lev),
29.3 (CH3 of Lev), 27.5 (CH2 of Lev); HRMS (ESI) calcd for
4.3.7. p-Tolyl 3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-1-thio-
b-D
-glucopyranoside (12)
Et3SiH (93 mL, 574 mmol) and BF3ꢀEt2O (12 mL, 95.5 mmol)
were added to a solution of 11 (34.4 g, 52.9 mmol) in dry CH2Cl2
(300 mL) at 0 °C. The reaction mixture was warmed to 25 °C over
4 h. The mixture was diluted with CH2Cl2, washed with satd NaH-
CO3, dried, and concentrated in vacuo. The residue was purified by
column chromatography (EtOAc/n-hexane, 1:3.5) to provide 12
(33.0 g, 99%) as a off-white solid: mp 100 °C; ½a D25
ꢁ19.9 (c 0.1,
ꢂ
CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.04 (d, J = 8.0 Hz, 1H, H-
Ar), 7.52–7.29 (m, 15H, H-Ar), 7.07 (d, J = 8.0 Hz, 2H, H-Ar), 5.01
(t, J = 9.5 Hz, 1H, H-2), 4.70 (s, 2H, CH2 of Bn), 4.57 (d, J = 10.0 Hz,
1H, H-1), 4.55 (dd, J = 11.9, 18.4 Hz, 2H, CH2 of Bn), 4.07–4.06 (m,
2H, CH2 of NPAc), 3.80–3.72 (m, 2H, H-6a0, H-6b0), 3.64 (t,
J = 9.3 Hz, 1H, H-4), 3.54 (t, J = 9.0 Hz, 1H, H-3), 3.50–3.46 (m, 1H,
H-5), 2.31 (s, 3H, CH3 of STol); 13C NMR (CDCl3, 150 MHz,) d
168.3 (OC@O), 148.8, 138.1, 137.8, 137.7, 133.1, 133.0, 129.3,
128.84–127.47, 124.9, 86.0 (C-1), 83.6 (C-3), 78.3 (C-5), 74.3 (CH2
of Bn), 73.3 (CH2 of Bn), 72.2 (C-2), 71.0 (C-4), 69.8 (C-6), 39.1
(CH2 of NPAc), 20.9 (CH3 of STol); HRMS (ESI) calcd for C35H35NO8S-
Na [M+Na]+: 652.1976, found: 652.1956.
C
33H35NO11Na [M+Na]+: 644.2102, found: 644.2083.
4.3.10. Chlorogenin 3b-O-{3,6-di-O-benzyl-4-O-levulinoyl-2-O-
(2-nitro)phenylacetyl]-b- -glucopyranoside} 6 -acetate (4)
D
a
To a solution of 14 (30.0 g, 48.3 mmol) in dry CH2Cl2 (300 mL)
were added CCl3CN (24.1 mL, 241 mmol) and DBU (3.6 mL,
24.1 mmol). After stirred for 2 h, the mixture was concentrated
and purified by column chromatography (EtOAc/hexane, 1:4) to
obtain imidated intermediate (30.0 g, 81%) as yellow oil. The imi-
date (30.0 g, 39.2 mmol) and acceptor 5 (10.3 g, 21.7 mmol) in
CH2Cl2 (400 mL) were stirred in the presence of 3 Å molecular
sieves (10 g, powdered) for 10 min. The mixture was cooled to
4.3.8. p-Tolyl 3,6-di-O-benzyl-4-O-levulinoyl-2-O-(2-
nitro)phenylacetyl-1-thio-b-
D
-glucopyranoside (13)
ꢁ25 °C and TMSOTf (787
lL, 4.3 mmol) was added. After stirred
LevOH (53.8 mL, 524 mmol), EDC (40.6 g, 262 mmol), and
DMAP (82.8 mg, 1.00 mmol) were added to a solution of compound
12 (33.0 g, 52.4 mmol) in dry CH2Cl2 (350 mL) under nitrogen. The
solution was stirred overnight at rt. The reaction mixture was di-
luted with CH2Cl2, filtered, and the filtrate was washed with water
and brine. The organic layers were separated and dried over MgSO4
and then filtered. The filtrate was concentrated under vacuum to
obtain the crude products, recrystallized from methanol to give
at ꢁ25 °C for 30 min, the solution was quenched by triethylamine
to adjust the pH value to be around 7. The solution was filtered,
concentrated, and purified by column chromatography (EtOAc/
hexane, 1:3) to afford 4 (14.1 g, 60%) as a off-white solid: mp
193 °C; ½a 2D5
ꢂ
ꢁ11.9 (c 0.05, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d
8.27 (d, J = 7.8 Hz, 1H, H-Ar), 7.98 (d, J = 7.6 Hz, 1H, H-Ar), 7.70–
7.69 (m, 1H, H-Ar), 7.58–7.56 (m, 1H, H-Ar), 7.30–7.13 (m, 10H,
H-Ar), 5.05 (t, J = 9.4 Hz, 1H, H-40), 5.03 (t, J = 8.4 Hz, 1H, H-20),
4.81 (d, J = 11.5 Hz, 1H, CH2 of Bn), 4.67 (d, J = 7.6 Hz, 1H, H-10),
4.64–4.62 (m, 1H, H-6), 4.52 (d, J = 11.3 Hz, 1H, CH2 of Bn), 4.51
(s, 2H, CH2 of Bn), 4.36–4.33 (m, 1H, H-16), 3.85 (t, J = 9.0 Hz, 1H,
H-30), 3.63–3.51 (m, 6H, H-3, H-50, H-6a0, H-6b0, CH2 of NPAc),
3.45–3.44 (m, 1H, H-26a), 3.35 (t, J = 10.9 Hz, 1H, H-26b), 2.57–
2.53 (m, 2H, CH2 of Lev), 2.45–2.15 (m, 2H, CH2 of Lev), 2.08 (s,
3H, CH3 of Lev), 2.01 (s, 3H, CH3 of Ac), 1.91–1.90 (m, 4H), 1.73–
1.52 (m, 13H), 1.29–1.06 (m, 8H), 0.94 (d, J = 7.0 Hz, 3H, H-21),
0.85 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27), 0.74 (s, 3H, H-
18), 0.60–0.58 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 206.15
(C@O), 171.5, 170.6, 162.9 (OC@O), 146.5, 138.1, 138.0, 132.8,
131.1, 131.1, 130.3, 129.0, 128.3–127.2, 125.9, 109.2 (C-22), 98.7
(C-10), 80.6 (C-16), 79.7 (C-30), 78.4 (C-3), 76.8 (C-20), 73.6 (CH2 of
Bn), 73.6 (CH2 of Bn), 73.4 (C-50), 72.3 (C-6), 70.8 (C-40), 69.7 (C-
60), 66.8 (C-26), 62.0, 55.9, 53.7, 48.5, 41.5, 40.5, 39.8 (CH2 of NPAc),
37.8, 37.6, 37.0, 36.7, 33.6, 31.6, 31.3, 30.2, 29.7 (CH3 of Lev), 28.9,
28.7, 28.2, 27.6, 21.4, 21.3 (CH3 of Ac), 20.8, 17.1 (C-27), 16.3 (C-
18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for C62H79NO15Na
[M+Na]+: 1100.5342, found: 1100.5353.
13 (36 g, 94%) as a white solid: mp 137 °C; ½a D25
ꢁ12.5 (c 0.04,
ꢂ
CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.03 (d, J = 8.0 Hz, 1H, Ar-
H), 7.51 (t, J = 7.4 Hz, 1H, Ar-H), 7.43 (t, J = 7.7 Hz, 1H, H-Ar), 7.36
(d, J = 8.0 Hz, 2H, Ar-H), 7.33–7.23 (m, 9H, H-Ar), 7.19 (d,
J = 7.2 Hz, 2H, H-Ar), 6.99 (d, J = 8.0 Hz, 2H, H-Ar), 4.98–4.97 (m,
2H, H-2, H-4), 4.56 (d, J = 11.7 Hz, 1H, CH2 of Bn), 4.54 (d,
J = 10.2 Hz, 1H, H-1), 4.50 (d, J = 11.6 Hz, 1H, CH2 of Bn), 4.48 (dd,
J = 14.1, 11.7 Hz, 2H, CH2 of Bn), 4.03 (d, J = 16.7 Hz, 1H, CH of
NPAc), 3.98 (d, J = 16.7 Hz, 1H, CH of NPAc), 3.69 (t, J = 9.1 Hz, 1H,
H-3), 3.57–3.55 (m, 3H, H-5, H-6a0, H-6b0), 2.58–2.51 (m, 2H, CH2
of Lev), 2.37–2.27 (m, 2H, CH2 of Lev), 2.27 (s, 3H, CH3 of STol),
2.08 (s, 3H, CH3 of Lev); 13C NMR (CDCl3, 150 MHz,) d 206.1
(C@O), 171.4, 168.2 (OC@O), 149.1, 138.1, 138.1, 138.1, 133.3,
133.1 (C-Ar), 129.6, 128.89–127.54, 125.1 (CH-Ar), 86.2 (C-1),
81.6 (C-3), 77.7 (C-5), 74.0 (CH2 of Bn), 73.5 (CH2 of Bn), 72.4 (C-
2), 70.7 (C-4), 69.6 (C-6), 39.2 (CH2 of NPAc), 37.6 (CH2 of Lev),
29.7 (CH3 of Lev), 27.7 (CH2 of Lev), 21.1 (CH3 of STol); HRMS
(ESI) calcd for C40H41NO10SNa [M+Na]+: 750.2343, found:
750.2319.
4.3.9. 3,6-Di-O-benzyl-4-O-levulinoyl-2-O-(2-
4.3.11. Chlorogenin 3b-O-(3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside) 6 -acetate (28)
D-
nitro)phenylacetyl-b-
D-glucopyranose (14)
a
NBS (1.78 g, 8.65 mmol) was added to a stirred solution of 13
Activated Zn powder (1.8 g, 27.8 mmol) and NH4Cl (893 mg,
(36.1 g, 49.5 mmol) in acetone (460 mL) and water (40 mL) at
16.7 mmol) were added to a solution of 4 (6.0 g, 5.6 mmol) in

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
125
CH2Cl2/methanol (1:1, 70 mL). The solution was stirred at rt over-
night. The reaction mixture was filtered, washed with methanol,
and the filtrate was concentrated. The residue was purified by col-
umn chromatography (toluene/acetone, 15:1) to afford 28 (4.1 g,
to the pH value to be around 7. The solution was filtered, concen-
trated, and purified by column chromatography.
4.3.14. Chlorogenin 3b-O-[2-O-(2,3,4-tri-O-benzoyl-b-
arabinopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (30)
L-
D-
81%) as yellow oil: ½a D25
ꢂ
ꢁ37.6 (c 0.09, CH2Cl2); 1H NMR (CDCl3,
600 MHz) d 7.27–7.17 (m, 10H, H-Ar), 4.87–4.86 (m, 1H, H-40),
4.75–4.74 (m, 1H, CH2 of Bn), 4.62–4.61 (m, 2H, H-6, CH2 of Bn),
4.45–4.44 (m, 2H, CH2 of Bn), 4.31–4.28 (m, 2H, H-10, H-16),
3.52–3.47 (m, 6H, H-3, H-50, H-30, H-6a0, H-6b0, H-20), 3.39–3.38
(m, 1H, H-26a), 3.29–3.28 (m, 1H, H-26b), 2.59–2.46 (m, 2H, CH2
of Lev), 2.37–2.24 (m, 2H, CH2 of Lev), 2.05 (s, 3H, CH3 of Lev),
1.98 (s, 3H, CH3 of Ac), 1.85–1.84 (m, 5H), 1.70–1.35 (m, 13H),
1.24–1.05 (m, 7H), 0.89 (s, 3H, H-21), 0.81 (s, 3H, H-19), 0.72 (d,
J = 6.2 Hz, 3H, H-27), 0.68 (s, 3H, H-18), 0.60–0.58 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 206.1 (C@O), 171.6, 170.6, (OC@O),
138.4, 138.1, 128.3–127.5, 109.1 (C-22), 101.2 (C-10), 81.4 (C-30),
80.5 (C-16), 78.6 (C-3), 74.2 (C-20), 74.1 (CH2 of Bn), 73.5 (C-50),
73.4 (CH2 of Bn), 72.2 (C-6), 70.9 (C-40), 69.7 (C-60), 66.8 (C-26),
62.0, 55.9, 53.6, 48.4, 41.5, 40.5, 39.7, 37.7, 37.6, 37.0, 37.6 (CH2
of Lev), 36.6, 33.6, 31.6, 31.2, 29.7 (CH3 of Lev), 29.1, 28.7, 28.7,
27.8 (CH2 of Lev), 21.3 (CH3 of Ac), 20.8, 17.0 (C-27), 16.3 (C-18),
a
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 15 (89.5 mg, 0.15 mmol) in CH2Cl2
afforded 30 (110 mg, 82%) as a off-white solid: mp 123 °C; ½a D25
ꢂ
+31.9 (c 0.05, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.03 (d,
J = 7.6 Hz, 2H, H-Ar), 7.90 (d, J = 7.5 Hz, 2H, H-Ar), 7.78 (d,
J = 7.6 Hz, 2H, H-Ar), 7.56–6.97 (m, 19H, H-Ar), 5.73 (t, J = 7.7 Hz,
1H, H-200), 5.62–5.60 (m, 1H, H-400), 5.52 (d, J = 8.5 Hz, 1H, H-300),
5.16 (d, J = 6.1 Hz, 1H, H-100), 4.83 (t, J = 7.8 Hz, 1H, H-40), 4.73 (d,
J = 12.2 Hz, 1H, CH2 of Bn), 4.64 (m, 1H, H-6), 4.61 (d, J = 7.7 Hz,
1H, H-10), 4.48 (s, 2H, CH2 of Bn), 4.39 (d, J = 12.4 Hz, 1H, CH2 of
Bn), 4.37 (m, 1H, H-16), 4.36 (m, 1H, H-5a00), 3.84 (d, J = 12.8 Hz,
1H, H-5b00), 3.72 (t, J = 8.5 Hz, 1H, H-20), 3.66 (m, 1H, H-3), 3.58
(t, J = 8.9 Hz, 1H, H-30), 3.51–3.44 (m, 4H, H-50, H-6a0, H-6b0, H-
26a), 3.38 (t, J = 10.9 Hz, 1H, H-26b), 2.46–2.30 (m, 2H, CH2 of
Lev), 2.30–2.23 (m, 2H, CH2 of Lev), 2.02 (s, 3H, CH3 of Lev),
2.00–1.96 (m, 2H), 1.91 (s, 3H, CH3 of Ac), 1.84–1.80 (m, 2H),
1.77–1.43 (m, 15H), 1.30–1.10 (m, 6H), 0.95 (d, J = 7.0 Hz, 3H, H-
21), 0.81 (s, 3H, H-19), 0.77 (d, J = 5.9 Hz, 3H, H-27), 0.74 (s, 3H,
H-18), 0.65–0.64 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 206.1
(C@O), 171.7, 170.6, 165.6, 165.5, 165.2 (OC@O), 138.5, 138.2,
133.3, 133.2, 133.0, 129.9–127.0, 109.2 (C-22), 100.6 (C-100), 100.1
(C-10), 82.3 (C-30), 81.4 (C-20), 80.6 (C-16), 78.2 (C-3), 75.2, 73.4
(CH2 of Bn), 73.2 (C-50), 72.3 (C-6), 71.3 (C-40), 70.8 (C-300), 70.5
(C-200), 69.8 (C-60), 68.4 (C-400), 66.8 (C-26), 62.7 (C-500), 62.1, 55.9,
53.72, 53.4, 48.5, 41.6, 40.5, 39.8, 37.7, 37.5 (CH2 of Lev), 37.1,
36.7, 33.6, 31.6, 31.3, 30.3, 29.6 (CH3 of Lev), 29.3, 28.7, 28.4,
27.6 (CH2 of Lev), 21.2 (CH3 of Ac), 17.1 (C-27), 16.4 (C-18), 14.4
(C-21), 13.2 (C-19); HRMS (ESI) calcd for C80H94O19Na [M+Na]+:
1381.6282, found: 1381.6176.
14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
C54H74O12Na
[M+Na]+: 937.5072, found: 937.5051.
4.3.12. Chlorogenin 3b-O-(3,6-di-O-benzyl-2-O-(2-
nitro)phenylacetyl-b-D-glucopyranoside) 6a-acetate (29)
Hydrazine acetate (1.0 g, 10.9 mmol) was added to a solution of
164 (6.0 g, 5.6 mmol) in CH2Cl2/methanol (1:1, 70 mL). After stir-
red for 8 h, the mixture was concentrated in vacuo and the residue
was purified by column chromatography (EtOAc/hexane, 1:3) to af-
ford 176 (3.8 g, 3.9 mmol, 70%) as yellow oil: ½a D25
ꢁ10.5 (c 0.057,
ꢂ
CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.28 (d, J = 8.2 Hz, 1H, H-
Ar), 7.98 (d, J = 8.1 Hz, 1H, H-Ar), 7.70 (t, J = 7.9 Hz, 1H, H-Ar),
7.58 (t, J = 7.9 Hz, 1H, H-Ar), 7.33–7.24 (m, 10H, H-Ar), 4.96 (t,
J = 7.8 Hz, 1H, H-20), 4.90 (d, J = 11.7 Hz, 1H, CH2 of Bn), 4.62–4.60
(m, 3H, H-10, H-6, CH2 of Bn), 4.57 (d, J = 12.1 Hz, 1H, CH2 of Bn),
4.53 (d, J = 12.1 Hz, 1H, CH2 of Bn), 4.35 (dd, J = 14.6, 7.3 Hz, 1H,
H-16), 3.75–3.58 (m, 5H, H-30, H-40, H-6a0, H-6b0, CH of NPAc),
3.53–3.51 (m, 1H, H-3), 3.45–3.44 (m, 2H, CH of NPAc, H-26a),
3.35 (d, J = 10.7 Hz, 1H, H-26b), 2.01 (s, 3H, CH3 of Ac), 1.99–1.58
(m, 12H), 1.51–1.40 (m, 3H), 1.28–0.95 (m, 10H), 0.93 (d,
J = 7.0 Hz, 3H, H-21), 0.84 (s, 3H, H-19), 0.77 (d, J = 6.2 Hz, 3H, H-
27), 0.73 (s, 3H, H-18), 0.64 (m, 1H); 13C NMR (CDCl3, 150 MHz) d
170.6, 168.1 (OC@O), 138.3, 137.7, 133.2, 132.9, 131.1, 128.6–
127.6, 125.1, 109.2 (C-22), 98.9 (C-10), 82.4 (C-30), 80.6 (C-16),
74.4 (C-3), 74.2 (C-40), 74.1 (CH2 of Bn), 73.9 (C-50), 73.6 (CH2 of
Bn), 73.6 (C-6), 72.3 (C-20), 72.1 (C-60), 71.9 (C-26), 66.8, 62.0,
55.9, 53.6, 48.6, 48.3, 41.5, 40.5, 39.7, 39.2 (CH2 of NPAc), 37.8,
37.1, 36.7, 33.6, 31.6, 31.3, 30.2, 28.7, 21.3 (CH3 of Ac), 20.8, 17.0
(C-27), 16.3 (C-18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
4.3.15. Chlorogenin 3b-O-[2-O-(2,3,4-tri-O-benzoyl-b-
fucopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (31)
L-
D
-
a
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 16 (91.6 mg, 0.15 mmol) in CH2Cl2
afforded 31 (111 mg, 82%) as a off-white solid: mp 130 °C; ½a D25
ꢂ
+39.9 (c 0.05, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.01 (d,
J = 8.0 Hz, 2H, H-Ar), 7.96 (d, J = 7.9 Hz, 2H, H-Ar), 7.74 (d,
J = 7.7 Hz, 2H, H-Ar), 7.50–7.20 (m, 19H, H-Ar), 5.77 (dd, J = 10.3,
8.0 Hz, 1H, H-200), 5.66 (d, J = 3.3 Hz, 1H, H-400), 5.45 (dd, J = 10.4,
3.4 Hz, 1H, H-300), 5.31 (d, J = 8.0 Hz, 1H, H-100), 5.11 (d,
J = 11.2 Hz, 1H, CH2 of Bn), 4.88 (t, J = 9.4 Hz, 1H, H-40), 4.75 (d,
J = 11.2 Hz, 1H, CH2 of Bn), 4.66 (td, J = 11.1, 4.7 Hz, 1H, H-6),
4.46 (br s, 2H, CH2 of Bn), 4.38 (q, J = 7.3 Hz, 1H, H-16), 4.28 (d,
J = 7.9 Hz, 1H, H-10), 4.04 (q, J = 6.5 Hz, 1H, H-500), 3.94 (t,
J = 8.5 Hz, 1H, H-20), 3.59 (t, J = 9.1 Hz, 1H, H-30), 3.51 (d,
J = 7.8 Hz, 1H, H-6a0), 3.49–3.45 (m, 3H, H-50, H-6b0, H-26a), 3.36
(t, J = 10.9 Hz, 1H, H-26b), 3.21–3.19 (m, 1H, H-3), 2.61–2.54 (m,
2H, CH2 of Lev), 2.42–2.37 (m, 2H, CH2 of Lev), 2.10 (s, 3H, CH3 of
Lev), 1.98 (s, 3H, CH3 of Ac), 1.93–1.90 (m, 2H), 1.76–1.75 (m,
1H), 1.73–1.43 (m, 14H), 1.29–1.26 (m, 5H), 1.14–1.09 (m, 6H),
0.95 (d, J = 6.9 Hz, 3H, H-21), 0.84 (s, 3H, H-19), 0.78 (d,
J = 6.3 Hz, 3H, H-27), 0.75 (s, 3H, H-18), 0.59–0.55 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 206.2 (C@O), 171.6, 170.8, 165.7, 165.4,
165.3 (OC@O), 138.5, 138.2, 133.4, 133.1, 133.1, 129.8–127.5,
109.3 (C-22), 102.8 (C-100), 99.6 (C-10), 81.0 (C-3), 80.6 (C-16),
79.85 (C-30), 77.8 (C-20), 74.2, 73.4 (CH2 of Bn), 73.2 (C-50), 72.5
(C-6), 72.1 (C-300), 71.1 (C-400), 70.5 (C-40), 70.5 (C-200), 69.8 (C-60),
69.5 (C-500), 66.8 (C-26), 62.1, 56.0, 53.8, 48.6, 41.6, 40.6, 39.8,
38.0 (CH3 of Lev), 37.7 (CH2 of Lev), 36.8, 36.6, 33.6, 31.6, 31.3,
C
57H73NO13Na [M+Na]+: 1002.4974, found: 1002.4935.
4.3.13. General procedure for glycosylation reaction
(compounds 30–49, 51–52)
A glycosyl trichloroacetimidate donor was readily prepared by
treatment of related 1-hydroxyl sugar (1 mmol = 1 equiv) in dry
CH2Cl2 (5–20 mL) with trichloroacetonitrile (5 mmol = 5 equiv)
and DBU (0.5 mmol = 0.5 equiv). The solution was stirred for 2 h
and concentrated and the residue was purified by column chroma-
tography to get glycosyl trichloroacetimidate donors (15–24).
Then, glycosyl trichloroacetimidate donor (1.8 mmol = 1.8 equiv)
and acceptor (1 mmol = 1 equiv) in dry CH2Cl2 (5–20 mL) were stir-
red in the presence of 3 Å molecular sieves (100–300 mg, pow-
dered) for 10 min. The mixture was cooled to ꢁ25 °C and TMSOTf
(0.2 mmol, 0.2 equiv) was added. On continuous stirring at
ꢁ25 °C for 30 min, the solution was quenched with triethylamine

126
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
30.3, 29.7, 29.5, 29.4, 28.7, 27.9 (CH2 of Lev), 21.1 (CH3 of Ac), 20.8,
37.7, 37.6 (CH2 of Lev), 37.0, 36.6, 33.6, 31.6, 31.3, 30.8, 29.6 (CH3
of Lev), 29.4, 28.8, 28.7, 27.7 (CH2 of Lev), 21.1 (CH3 of Ac), 20.8,
17.0 (C-27), 16.4 (C-18), 14.4 (C-21), 13.3 (C-19); HRMS (ESI) calcd
for C80H94O19Na [M+Na]+: 1381.6282, found: 1381.6291.
17.1 (C-27), 16.4 (C-18), 16.2 (C-600), 14.4 (C-21), 13.3 (C-19); HRMS
(ESI) calcd for
1395.6330.
C
81H96O19Na [M+Na]+: 1395.6438, found:
4.3.16. Chlorogenin 3b-O-[2-O-(2,3,4-tri-O-benzoyl-b-
xylopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (32)
L
-
4.3.18. Chlorogenin 3b-O-[2-O-(2,3,4,6-tetra-O-benzoyl-
mannopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (34)
a-D-
D-
D-
a
a
According to the general procedure for glycosylation, treatment
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.1 mmol) and 17 (89.5 mg, 0.15 mmol) in CH2Cl2
of 28 (90 mg, 0.10 mmol) and 19 (109 mg, 0.15 mmol) in CH2Cl2
afforded 32 (110 mg, 82.3%) as a white solid: mp, 116 °C; ½a D25
ꢂ
afforded 34 (90 mg, 61%) as a white solid: mp 127 °C; ½a D25
ꢁ1.3
ꢂ
+7.5 (c 0.04, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.99 (d,
J = 8.0 Hz, 2H, H-Ar), 7.93 (d, J = 7.2 Hz, 2H, H-Ar), 7.88 (d,
J = 7.9 Hz, 2H, H-Ar), 7.56–7.20 (m, 19H, H-Ar), 5.70 (t, J = 8.4 Hz,
1H, H-300), 5.45 (dd, J = 6.7, 8.6 Hz, 1H, H-200), 5.31–5.30 (m, 1H,
H-400), 5.26 (d, J = 6.7 Hz, 1H,H-100), 4.93 (d, 1H, J = 11.6 Hz, CH2 of
Bn), 4.88 (t, J = 9.1 Hz, 1H, H-40), 4.66 (d, J = 11.6 Hz, 1H, CH2 of
Bn), 4.63–4.61 (m, 1H, H-6), 4.45 (br s, 2H, CH2 of Bn), 4.37–4.33
(m, 2H, H-16, H-5a00), 4.30 (d, J = 7.9 Hz, 1H, H-10), 3.81 (t,
J = 8.2 Hz, 1H, H-20), 3.56 (t, J = 9.2 or 9.7 Hz, 1H, H-30), 3.49–3.53
(m, 2H, H-5b00, H-6a0), 3.45–3.40 (m, 3H, H-26a, H-50, H-6b0), 3.36
(t, J = 10.9 Hz, 1H, H-26b), 3.23–3.20 (m, 1H, H-3), 2.60–2.49 (m,
2H,CH2 of Lev), 2.37–2.23 (m, 2H,CH2 of Lev), 2.09 (s, 6H, CH3 of
Lev, CH3 of Ac), 2.06–1.82 (m, 4H), 1.78–1.42 (m, 14H), 1.32–1.06
(m, 4H), 0.95 (d, J = 7.0 Hz, 3H, H-21), 0.85–0.84 (m, 3H), 0.81(s,
3H, H-19), 0.78 (d, J = 6.3 Hz, 3H, H-27), 0.75 (s, 3H, H-18), 0.58–
0.55 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 206.2 (C@O), 171.5,
171.2, 165.52, 165.3, 165.0 (OC@O), 149.5, 149.4, 149.2, 138.4,
138.2, 135.6, 135.4, 135.2, 133.3, 133.2, 133.2, 129.8–127.4,
123.3, 123.1, 123.0, 109.2 (C-22), 102.2 (C-10), 99.8 (C-100), 80.6
(C-16), 80.33 (C-3), 80.32 (C-30), 78.1 (C-20), 74.7 (CH2 of Bn),
73.3 (CH2 of Bn), 73.2 (C-50), 72.3 (C-6), 71.6 (C-300), 71.5 (C-200),
70.8 (C-40), 69.8 (C-400), 69.8 (C-60), 66.8 (C-26), 62.1, 62.0 (C-500),
56.0, 53.8, 48.4, 41.6, 40.5, 39.8, 38.0, 37.7 (CH2 of Lev), 36.8,
36.61, 33.60, 31.6, 31.5, 31.3, 30.3, 29.7 (CH3 of Lev), 29.3, 29.1,
27.8 (CH2 of Lev), 21.3 (CH3 of Ac), 20.8, 17.1 (C-27), 16.4 (C-18),
(c 0.08, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.06 (d, J = 8.4 Hz,
2H, H-Ar), 8.01 (d, J = 7.1 Hz, 2H, H-Ar), 7.81 (d, J = 8.5 Hz, 2H, H-
Ar), 7.74 (d, J = 8.3 Hz, 2H, H-Ar), 7.54–7.10 (m, 22H, H-Ar), 6.03
(t, J = 10.3 Hz, 1H, H-400), 5.86 (dd, J = 2.6, 10.2 Hz, 1H, H-300),
5.66–5.65 (m, 2H, H-100, H-200), 5.10 (t, J = 9.4 Hz, 1H, H-40), 4.92
(d, J = 11.5 Hz, 1H, CH2 of Bn), 4.84 (d, J = 11.5 Hz, 1H, CH2 of Bn),
4.64 (d, J = 7.6 Hz, 1H, H-10), 4.57–4.54 (m, 2H, H-500, H-6), 4.53
(s, 2H, CH2 of Bn), 4.35–4.34 (m, 1H, H-16), 4.19 (dd, J = 12.2,
1.9 Hz, 1H, H-6a00), 4.00 (dd, J = 12.3, 4.3 Hz, 1H, H-6b00), 3.81–
3.76 (m, 2H, H-20, H-30), 3.63–3.56 (m, 4H, H-50, H-3, H-6a0, H-
6b0), 3.44–3.43 (m, 1H, H-26a), 3.35 (t, J = 10.5 Hz, 1H, H-26b),
2.60–2.52 (m, 2H, CH2 of Lev), 2.45–2.30 (m, 2H, CH2 of Lev),
2.07 (s, 3H, CH3 of Lev), 2.04–2.02 (m, 2H), 1.91 (s, 3H, CH3 of
Ac), 1.88–1.81 (m, 4H), 1.75–1.41 (m, 12H), 1.29–1.18 (m, 5H),
1.10–0.93 (m, 2H), 0.94 (d, J = 7.0 Hz, 3H, H-21), 0.84 (s, 3H, H-
19), 0.77 (d, J = 6.3 Hz, 3H, H-27), 0.72 (s, 3H, H-18), 0.65–0.62
(m, 1H); 13C NMR (CDCl3, 150 MHz) d 206.3 (C@O), 171.1, 170.9,
166.8, 166.0, 165.3, 164.7 (OC@O), 138.1, 137.6, 133.3, 133.3,
133.2, 132.8, 130.0–127.1, 109.2 (C-22), 101.6 (C-10), 97.6 (C-100),
81.0 (C-30), 80.6 (C-16), 78.9 (C-3), 75.9 (C-20), 75.3, 73.5 (CH2 of
Bn), 73.3 (C-50), 72.4 (C-500), 72.2 (C-40), 70.1 (C-200), 70.1 (C-300),
69.7 (C-60), 68.7 (C-6), 66.8 (C-26), 66.6 (C-400), 62.4 (C-600), 62.1,
56.0, 53.8, 48.4, 41.5, 40.5, 39.8, 37.7 (CH2 of Lev), 37.7, 37.2,
36.6, 33.5, 31.6, 31.3, 30.3, 29.6 (CH3 of Lev), 29.3, 28.7, 28.4,
27.9 (CH2 of Lev), 21.3 (CH3 of Ac), 20.9, 17.1 (C-27), 16.4 (C-18),
14.4 (C-21), 13.1 (C-19); HRMS (ESI) calcd for C88H100O21Na
[M+Na]+: 1515.6649, found: 1515.6770.
14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
C80H94O19Na
[M+Na]+: 1381.6282, found: 1381.6168.
4.3.17. Chlorogenin 3b-O-[2-O-(2,3,4-tri-O-benzoyl-b-
xylopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (33)
D
-
4.3.19. Chlorogenin 3b-O-[2-O-(2,3,4,6-tetra-O-benzoyl-
glucopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (35)
a-D-
D-
D-
a
a
According to the general procedure for glycosylation, treatment
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 18 (89.5 mg, 0.15 mmol) in CH2Cl2
of 28 (90 mg, 0.10 mmol) and 20 (109.3 mg, 0.15 mmol) in CH2Cl2
afforded 33 (66 mg, 49%) as a white solid: mp 121 °C; ½a D25
ꢂ
ꢁ26.4
afforded 35 (50 mg, 34%) as a white solid: mp 112 °C; ½a D25
ꢁ1.4 (c
ꢂ
(c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.98 (d, J = 7.1 Hz,
2H, H-Ar), 7.96 (d, J = 8.2 Hz, 2H, H-Ar), 7.80 (d, J = 7.1 Hz, 2H, H-
Ar), 7.53–7.03 (m, 19H, H-Ar), 5.61 (t, J = 6.0 Hz, 1H, H-300), 5.34
(t, J = 4.3 Hz, 1H, H-200), 5.31 (d, J = 4.2 Hz, 1H, H-100), 5.22 (q,
J = 4.1 Hz, 1H, H-400), 4.83 (t, J = 7.8 Hz, 1H, H-40), 4.68 (d,
J = 11.8 Hz, 1H, CH2 of Bn), 4.63–4.61 (m, 2H, H-6, H-5a00), 4.55
(d, J = 7.6 Hz, 1H, H-10), 4.49 (s, 2H, CH2 of Bn), 4.46 (d,
J = 11.7 Hz, 1H, CH2 of Bn), 4.36 (dd, J = 6.9, 15.0 Hz, 1H, H-16),
3.78 (dd, J = 7.9, 7.7 Hz, 1H, H-20), 3.68–3.64 (m, 2H, H-30, H-5b00),
3.60–3.47 (m, 4H, H-3, H-50, H-6a0, H-6b0), 3.51–3.49 (m, 1H, H-
26a), 3.35 (t, J = 10.7 Hz, 1H, H-26b), 2.52–2.40 (m, 2H, CH2 of
Lev), 2.30–2.07 (m, 2H, CH2 of Lev), 2.07 (m, 6H, CH3 of Lev, CH3
of Ac), 1.93–1.83 (m, 5H), 1.76–1.41 (m, 13H), 1.29–1.00 (m, 7H),
0.94 (d, J = 6.9 Hz, 3H, H-21), 0.82 (s, 3H, H-19), 0.77 (d,
J = 6.9 Hz, 3H, H-27), 0.73 (s, 3H, H-18), 0.61–0.60 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 206.0 (C@O), 171.6, 170.7, 165.4, 165.1,
165.1 (OC@O), 138.1, 138.1, 133.3, 133.2, 133.1, 129.8–127.1,
109.2 (C-22), 100.9 (C-10), 99.0 (C-100), 83.0 (C-30), 80.6 (C-16),
79.7 (C-3), 78.3 (C-20), 75.0, 73.4 (CH2 of Bn), 73.3 (C-50), 72.1 (C-
6), 71.5 (C-40), 69.9 (C-200), 69.8 (C-60), 69.5 (C-300), 68.5 (C-400),
66.8 (C-26), 62.1, 60.4 (C-500), 55.9, 53.7, 48.5, 41.5, 40.5, 39.8,
0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.02 (d, J = 7.2 Hz, 2H, H-
Ar), 7.83 (d, J = 7.2 Hz, 2H, H-Ar), 7.76 (t, J = 7.2 Hz, 4H, H-Ar), 7.50–
7.35 (m, 7H, H-Ar), 7.31–7.27 (m, 7H, H-Ar), 7.23–7.18 (m, 7H, H-
Ar), 7.00 (d, J = 7.2 Hz, 2H, H-Ar), 5.81 (t, J = 7.8 Hz, 1H, H-200), 5.74
(t, J = 7.8 Hz, 1H, H-300), 5.53 (t, J = 7.8 Hz, 1H, H-400), 5.33 (d,
J = 7.7 Hz, 1H, H-10), 4.80 (t, J = 7.6 Hz, 1H, H-40), 4.67–4.64 (m,
3H, H-6a00, H6b00, CH2 of Bn), 4.56 (d, J = 7.9 Hz, 1H, H-100), 4.47–
4.43 (m, 3H, H-3, CH2 of Bn), 4.36–4.35 (m, 1H, H-20), 4.34 (d,
J = 12 Hz, 1H, CH2 of Bn), 4.07–4.04 (m, 1H, H-6a), 3.73–3.67 (m,
3H, H-6, H-30, H-40), 3.64–3.63 (m, 1H, H-50), 3.55 (t, J = 10.1 Hz
1H, H-6a0), 3.53–3.44 (m, 5H, H-6b0, H6a00, H6b00, H-26a, H-500),
3.36 (t, J = 10.9, 1H, H-26b), 2.43–2.33 (m, 2H, CH2 of Lev), 2.22–
2.15 (m, 2H, CH2 of Lev), 2.03 (s, 3H, CH3 of Lev), 2.02 (s, 3H, CH3
of Ac), 1.96–1.84 (m, 6H), 1.76–1.75 (m, 1H), 1.69–1.37 (m, 14H),
1.27–1.03 (m, 4H), 0.94 (d, J = 7.0 Hz, 3H, H-21), 0.79 (d,
J = 6.3 Hz, 3H, H-27), 0.73 (s, 3H, H-19), 0.58 (s, 3H, H-18), 0.65–
0.62 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 171.6, 170.7, 166.1,
165.8, 165.1, 165.1, 138.5, 138.2, 133.4, 133.2, 133.1, 129.9,
129.8, 129.7, 129.1, 128.8, 128.4, 128.3, 128.3, 128.1, 127.6,
127.5, 127.2, 127.1, 109.3 (C-22), 100.4 (C-100), 100.4 (C-10), 82.4,
81.0, 80.7, 79.0, 75.2, 73.4, 73.1, 73.1, 72.7, 72.4, 72.3, 71.3, 69.8,

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
127
69.6, 66.9, 63.1, 62.1, 58.5, 55.9, 53.5, 48.4, 41.6, 40.6, 39.8, 37.6,
36.9, 36.6, 33.6, 31.6, 31.3, 30.3, 29.6, 29.2, 29.2, 28.7, 27.6, 21.5,
20.9, 18.4, 17.1, 16.4, 14.5, 13.3; HRMS (ESI) calcd for C88H100O21Na
[M+Na]+: 1515.6649, found: 1515.6680.
109.2 (C-22), 101.0 (C-1000), 100.1 (C-100), 99.9 (C-10), 82.3 (C-30),
80.7 (C-20), 80.6 (C-16), 78.2 (C-3), 75.8 (C-400), 75.1 (CH2 of Bn),
73.3 (CH2 of Bn), 73.18 (C-300), 73.05 (C-50), 73.04 (C-500), 72.6 (C-
200), 72.1 (C-6), 71.9 (C-3000), 71.28 (C-40), 71.26 (C-5000), 69.8 (C-
2000), 69.7 (C-60), 67.4 (C-4000), 66.9 (C-26), 62.4 (C-600), 62.1, 60.7
(C-6000), 55.8, 53.4, 48.4, 41.6, 40.5, 39.7, 37.7, 37.5 (CH2 of Lev),
36.8, 36.5, 33.6, 31.7, 31.3, 30.3, 29.6 (CH3 of Ac), 29.0, 28.9, 28.7,
27.6 (CH2 of Lev), 21.4 (CH3 of Lev), 20.8, 17.1 (C-27), 16.4 (C-19),
14.4 (C-21), 13.0 (C-18); HRMS (ESI) calcd for C115H122O29Na
[M+Na]+: 1990.7998, found: 1990.7787.
4.3.20. Chlorogenin 3b-O-[2-O-(2,3,4,6-tetra-O-benzoyl-b-
galactopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (36)
D-
D
-
a
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 21 (109.3 mg, 0.15 mmol) in CH2Cl2
afforded 36 (52 mg, 35%) as a white solid: mp 76 °C; ½a D25
ꢂ
+23.8 (c
0.08, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.07 (d, J = 6.8 Hz, 2H, H-
Ar), 7.99 (d, J = 8.4 Hz, 2H, H-Ar), 7.73 (m, 4H, H-Ar), 7.47–7.15 (m,
22H, H-Ar), 5.99 (d, J = 3.6 Hz, 1H, H-400), 5.82 (dd, J = 9.5, 10.2 Hz,
1H, H-200), 5.52 (dd, J = 4.4, 10.2 Hz, 1H, H-300), 5.33 (d, J = 8.5 Hz,
1H, H-100), 4.81–4.80 (m, 1H, H-40), 4.74 (d, J = 12.5 Hz, 1H, CH2 of
Bn), 4.67–4.64 (m, 3H, H-6a00, H-10, H-6), 4.48 (s, 2H, CH2 of Bn),
4.41–4.37 (m, 3H, H-16, CH2 of Bn, H-6b00), 4.28–4.27 (m, 1H, H-
500), 3.76 (t, J = 8.5 Hz, 1H, H-20), 3.71–3.70 (m, 1H, H-3), 3.62 (t,
J = 8.3 Hz, 1H, H-30), 3.50–3.45 (m, 4H, H-50, H-6a0, H-6b0, H-26a),
3.37 (t, J = 11.0 Hz, 1H, H-26b), 2.45–2.29 (m, 2H, CH2 of Lev),
2.21–2.15 (m, 2H, CH2 of Lev), 2.02 (s, 3H, CH3 of Lev), 1.96 (s,
3H, CH3 of Ac), 1.95–1.74 (m, 4H), 1.71–1.33 (m, 15H), 1.23–1.21
(m, 4H), 1.01–0.98 (m, 2H), 0.95 (d, J = 7.2 Hz, 3H, H-21), 0.83 (s,
3H, H-19), 0.78 (d, J = 6.1 Hz, 3H, H-27), 0.73 (s, 3H, H-18), 0.63–
0.62 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 206.1 (C@O), 171.6,
170.6, 165.7, 165.55, 165.52, 165.2 (OC@O), 138.6, 138.1, 133.5,
133.2, 133.2, 133.0, 130.0–126.9, 109.2 (C-22), 100.8 (C-100), 99.8
(C-10), 82.2 (C-30), 81.4 (C-20), 80.6 (C-16), 78.2 (C-3), 75.2, 73.4
(CH2 of Bn), 73.1 (C-50), 72.4 (C-6), 71.9 (C-300), 71.4 (C-500), 71.3
(C-40), 70.5 (C-200), 69.7 (C-60), 67.8 (C-400), 66.8 (C-26), 62.4, 62.1,
61.2 (C-600), 55.9, 53.6, 48.3, 41.6, 40.5, 39.8, 37.6 (CH2 of Lev),
37.4, 36.7, 33.5, 31.6, 31.3, 30.3, 29.6 (CH3 of Lev), 29.1, 28.9,
28.7, 27.5 (CH2 of Lev), 21.2 (CH3 of Ac), 20.8, 17.1 (C-27), 16.4
(C-18), 14.4 (C-21), 13.3 (C-19); HRMS (ESI) calcd for C88H100O21Na
[M+Na]+: 1515.6649, found: 1515.6642.
4.3.22. Chlorogenyl 3b-O-[2-O-(2,3,4-tri-O-benzoyl-
rhamnopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (38)
a-L-
D-
a
According to the general procedure for glycosylation, treatment
of 28 (2.00 g, 2.19 mmol) and 23 (2.04 g, 3.28 mmol) in CH2Cl2
afforded 38 (1.46 g, 49%) as a white solid: mp, 125 °C; ½a D25
ꢂ
+145.0 (c 0.12, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.98 (d,
J = 7.9 Hz, 2H, H-Ar), 7.92 (d, J = 7.5 Hz, 2H, H-Ar), 7.80 (d,
J = 8.0 Hz, 2H, H-Ar), 7.56 (t, J = 7.4 Hz, 1H, H-Ar), 7.50 (t,
J = 7.4 Hz, 1H, H-Ar), 7.45–7.21 (m, 14H, H-Ar), 7.12 (t, J = 7.5 Hz,
2H, H-Ar), 7.04 (t, J = 7.5 Hz, 1H, H-Ar), 5.75 (m, 2H, H-200, H-300),
5.60 (t, J = 9.8 Hz, 1H, H-400), 5.38 (s, 1H,H-100), 4.99 (t, J = 9.4 Hz,
1H, H-40), 4.82 (d, 1H, J = 11.2 Hz, CH2 of Bn), 4.72–4.66 (m, 3H,
H-6, H-500, CH2 of Bn), 4.63 (d, J = 7.6 Hz, 1H, H-10), 4.54 (s, 2H,
CH2 of Bn), 4.38 (dd, J = 7.4, 15.0 Hz, 1H, H-16), 3.83 (t, J = 9.1 Hz,
1H, H-30), 3.80–3.72 (m, 2H, H-20, H-3), 3.60 (m, 2H, H-50, H-6a0),
3.55 (m, 1H, H-6b0), 3.44–3.43 (m, 1H, H-26a), 3.36 (t, J = 11.0 Hz,
1H, H-26b), 2.60–2.50 (m, 2H, CH2 of Lev), 2.40–2.20 (m, 2H, CH2
of Lev), 2.15–2.14 (m, 1H), 2.10 (s, 3H, CH3 of Lev), 2.07–2.06 (m,
1H), 2.03 (s, 3H, CH3 of Ac), 1.94–1.84 (m, 4H), 1.76–1.43 (m,
12H), 1.30 (d, J = 6.2 Hz, 3H, CH3-600), 1.29–1.09 (m, 6H), 0.95 (d,
J = 7.0 Hz, 3H, H-21), 0.87–0.86 (m, 1H), 0.78 (d, J = 6.3 Hz, 3H, H-
27), 0.72 (s, 3H, H-19), 0.69 (s, 3H, H-18), 0.67–0.66 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 206.0 (C@O), 171.6, 170.7, 165.9, 165.5,
165.2 (OC@O), 138.1, 137.7, 133.2, 133.2, 132.9, 129.8, 129.6,
129.6, 129.4, 129.3, 129.2, 128.4–128.1, 127.7–127.4, 109.1 (C-
22), 98.4 (C-10), 97.6 (C-100), 83.7 (C-30), 80.5 (C-16), 76.7 (C-3),
76.3 (C-20), 75.3 (CH2 of Bn), 73.4 (CH2 of Bn), 72.3 (C-6), 71.77
(C-40), 71.77 (C-400), 70.5 (C-200), 70.0 (C-300), 69.7 (C-60), 66.8 (C-
26), 66.7 (C-500), 62.0, 55.8, 53.6, 48.2, 41.5, 40.5, 39.7, 37.7, 37.6
(CH2 of Lev), 37.1, 36.6, 33.6, 31.6, 31.3, 30.2, 29.6 (CH3 of Lev),
29.0, 28.7, 27.9, 27.7 (CH2 of Lev), 21.2 (CH3 of Ac), 20.7, 17.4 (C-
600), 17.0 (C-27), 16.3 (C-19), 14.4 (C-21), 13.0 (C-18); HRMS (ESI)
calcd for C81H96O19Na [M+Na]+: 1395.6438, found: 1395.6329.
4.3.21. Chlorogenin 3b-O-{2-O-[2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-
tetra-O-benzoyl-b-
D
-galactopyranosyl)-b-
D-glucopyranosyl]-3,6-
di-O-benzyl-4-O-levulinoyl-b-
D
-glucopyranoside} 6 -acetate
a
(37)
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 22 (179 mg, 0.15 mmol) in CH2Cl2
afforded 37 (93 mg, 48%) as a white solid: mp 129 °C; ½a D25
ꢂ
+3.0
(c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.02 (d, J = 7.9 Hz,
2H, H-Ar), 7.95–7.88 (m, 7H, H-Ar), 7.85 (d, J = 7.9 Hz, 2H, H-Ar),
7.77 (d, J = 7.9 Hz, 2H, H-Ar), 7.68 (d, J = 8.0 Hz, 2H, H-Ar), 7.76 (t,
J = 7.6 Hz, 1H, H-Ar), 7.54–7.53 (m, 2H, H-Ar), 7.47–7.36 (m, 8H,
H-Ar), 7.32–7.16 (m, 15H, H-Ar), 7.12 (t, J = 7.7 Hz, 2H, H-Ar),
6.98 (d, J = 7.1 Hz, 2H, H-Ar), 5.72–5.63 (m, 3H, H-300, H-4000, H-
2000), 5.44 (t, J = 8.1 Hz, 1H, H-200), 5.27 (m, 1H, H-3000), 5.18 (d,
J = 8.0 Hz, 1H, H-100), 4.87 (d, J = 8.0 Hz, 1H, H-1000), 4.76 (t,
J = 9.0 Hz, 1H, H-40), 4.59–4.56 (m, 3H, H-6a00, H-6, CH2 of Bn),
4.50 (d, J = 7.4 Hz, 1H, H-10), 4.45–4.44 (m, 1H, CH2 of Bn), 4.43–
4.42 (m, 3H, H-6b00, CH2 of Bn), 4.39–4.36 (m, 1H, H-16), 4.34 (t,
J = 9.5 Hz, 1H, H-400), 4.27 (d, J = 12.1 Hz, 1H, CH2 of Bn), 3.80–
3.79 (m, 1H, H-5000), 3.73–3.71 (m, 2H, H-500, H-6a000), 3.64–3.60
(m, 2H, H-20, H-6b000), 3.55–3.54 (m, 1H, H-3), 3.51–3.35 (m, 5H,
H-30, H-6a0, H-6b0, H-26, H-50), 2.43–2.29 (m, 2H, CH2 of Lev),
2.17–2.15 (m, 2H, CH2 of Lev), 2.06 (s, 3H, CH3 of Lev), 2.00 (s,
3H, CH3 of Ac), 1.90–1.88 (m, 5H), 1.80–1.53 (m, 8H), 1.51–1.03
(m, 9H), 0.85–0.82 (m, 2H), 0.96 (d, J = 6.9 Hz, 3H, H-21), 0.78 (d,
J = 6.3 Hz, 3H, H-27), 0.75 (s, 3H, H-19), 0.72–0.70 (m, 1H), 0.57
(s, 3H, H-18), 0.55–0.52 (m, 1H); 13C NMR (CDCl3, 150 MHz) d
206.1 (C@O), 171.5, 170.8, 165.7, 165.5, 165.36, 165.35, 165.30,
165.2, 164.8 (OC@O), 138.4, 138.1, 133.4–133.0, 129.9–127.1,
4.3.23. Chlorogenin 3b-O-{2-O-[2,3-di-O-isopropylidene-4-O-
(2,3,4-tri-O-benzoyl-
rhamnopyranosyl]-3,6-di-O-benzyl-4-O-levulinyl-b-
glucopyranoside} 6 -acetate (39)
a-L-rhamnopyranosyl)-a-L-
D
-
a
According to the general procedure for glycosylation, treatment
of 28 (90 mg, 0.10 mmol) and 24 (119 mg, 0.15 mmol) in CH2Cl2
afforded 39 (73 mg, 48%) as a white solid: mp 136 °C; ½a D25
ꢂ
+19.9
(c 0.01, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.10 (d, J = 7.1 Hz,
2H, H-Ar), 7.93 (d, J = 7.2H, H-Ar), 7.76 (d, J = 7.2 Hz, 2H, H-Ar),
7.60–7.19 (m, 19H, H-Ar), 5.75 (m, 1H, H-3000), 5.71 (m, 1H, H-
2000), 5.63 (t, J = 9.8 Hz, 1H, H-4000), 5.56 (d, J = 1.4 Hz, 1H, H-1000),
5.38 (s, 1H, H-100), 4.98 (m, 1H, H-40), 4.75 (m, 1H, H-6), 4.67 (dd,
J = 11.2, 14.6 Hz, 2H, CH2 of Bn), 4.51 (m, 3H, CH2 of Bn, H-10),
4.33 (dd, J = 7.3, 15.6 Hz, 1H, H-16), 4.21–4.12 (m, 3H, H-300, H-500,
H-5000), 4.07 (d, J = 5.6 Hz, 1H, H-200), 3.69 (m, 3H, H-20, H-30, H-3),
3.59–3.53 (m, 4H, H-400, H-50, H-6a0, H-6b0), 3.44 (m, 1H, H-26a),
3.34 (t, J = 11.1 Hz, 1H, H-26b), 2.64–2.52 (m, 2H, CH2 of Lev),
2.40–2.29 (m, 2H, CH2 of Lev), 2.11 (s, 3H, CH3 of Ac), 2.06 (s, 3H,
CH3 of Lev), 1.97–1.88 (m, 4H), 1.79–1.51 (m, 14H), 1.49 (s, 3H,
CCH3), 1.36 (d, J = 6.3 Hz, 3H, H-600), 1.33 (d, J = 6.3 Hz, 3H, H-6000),

128
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
1.27 (s, 3H, C(CH3)2), 1.21 (m, 3H), 1.09–1.00 (m, 3H), 0.94 (s, 3H,
H-19), 0.92 (d, J = 7.0 Hz, 3H, H-21), 0.88–0.87 (m, 1H), 0.77 (d,
J = 6.2 Hz, 3H, H-27), 0.67–0.65 (m, 1H), 0.59 (s, 3H, H-18); 13C
NMR (CDCl3, 150 MHz) d 206.1 (C@O), 171.7, 170.4, 165.7, 165.3,
165.2 (OC@O), 138.1, 137.6, 133.2, 133.2, 132.9, 129.9–127.6,
109.4 (C(CH3)2), 109.2 (C-22), 98.9 (C-10), 97.5 (C-100), 95.9 (C-1000),
82.9 (C-30), 80.6 (C-16), 77.9 (C-300), 77.2 (C-60), 77.0 (C-3), 76.5
(C-20), 76.0 (C-200), 75.0 (CH2 of Bn), 73.5 (CH2 of Bn), 73.4 (C-50),
72.4 (C-6), 71.96 (C-40), 71.90 (C-4000), 70.9 (C-2000), 69.9 (C-60),
69.8 (C-3000), 67.2 (C-5000), 66.8 (C-26), 64.3 (C-500), 62.0, 55.9, 53.7,
48.4, 41.5, 40.5, 39.8, 37.8, 37.6 (CH2 of Lev), 37.0, 36.8, 33.5,
31.6, 31.3, 30.3, 29.7 (CH3 of Ac), 28.8, 28.7, 27.8 (CH2 of Lev),
26.3, 21.3 (CH3 of Lev), 20.9, 18.1 (C-600), 17.6 (C-6000), 17.0 (C-27),
16.2 (C-18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
1.98–1.83 (m, 6H), 1.74 (m, 1H), 1.71–1.27 (m, 15H), 1.11–1.09
(m, 3H), 1.20 (d, J = 6.4 Hz, 3H, H-600), 0.94 (d, J = 7.0 Hz, 3H, H-
21), 0.88 (m, 2H), 0.82 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27),
0.73 (s, 3H, H-18), 0.64 (m, 1H); 13C NMR (CDCl3, 150 MHz) d
171.1, 168.1, 165.8, 165.5, 165.3 (OC@O), 149.1, 138.6, 133.4,
133.2, 133.1, 132.8, 129.9–127.1, 109.2 (C-22), 100.2 (C-100), 98.5
(C-10), 83.1 (C-30), 80.6 (C-16), 77.6 (C-3), 74.8 (C-40), 74.7 (CH2 of
Bn), 74.49 (C-50), 74.40 (C-20), 73.6 (CH2 of Bn), 72.3 (C-6), 72.0
(C-300), 71.1 (C-400), 70.3 (C-200), 69.5 (C-500), 66.8 (C-26), 62.1, 60.3
(C-60), 55.9, 53.7, 48.3, 41.6, 40.5, 39.8, 39.0 (CH2 of NPAc), 37.8,
37.0, 36.7, 33.6, 31.6, 31.3, 30.3, 28.8, 28.7, 28.2, 22.6, 21.3 (CH3
of Ac), 20.8, 17.11 (C-27), 16.4 (C-18), 16.0 (C-600), 14.4 (C-21),
13.2 (C-19); HRMS (ESI) calcd for
1460.6340, found: 1460.6220.
C
84H95NO20Na [M+Na]+:
C
90H110O23Na [M+Na]+: 1581.7330, found: 1581.7284.
4.3.26. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-b-
xylopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
glucopyranoside] 6 -acetate (42)
L-
4.3.24. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-b-
arabinopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-
b- -glucopyranoside] 6 -acetate (40)
According to the general procedure for glycosylation, treatment
L
-
D-
a
D
a
According to the general procedure for glycosylation, treatment
of 29 (90 mg, 0.09 mmol) and 17 (84 mg, 0.14 mmol) in CH2Cl2
of 29 (90 mg, 0.09 mmol) and 15 (83 mg, 0.14 mmol) in CH2Cl2
afforded 42 (72 mg, 55%) as a white solid: mp 111 °C; ½a D25
ꢁ3.1
ꢂ
afforded 40 (115 mg, 89%) as a white solid: mp 145 °C; ½a D25
ꢂ
(c 0.03, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.82–7.92 (m, 8H,
H-Ar), 7.55–7.38 (m, 4H, H-Ar), 7.39–7.25 (m, 15H, H-Ar), 7.09
(m, 2H, H-Ar), 5.70 (t, J = 8.8 Hz, 1H, H-300), 5.38 (dd, J = 7.1,
9.2 Hz, 1H, H-200), 5.26–5.24 (m, 1H, H-400), 5.15–5.13 (m, 1H, H-
100), 4.88 (dd, J = 7.6, 9.4 Hz, 1H, H-20), 4.65 (m, 1H, H-6), 4.61 (m,
2H, CH2 of Bn), 4.50 (d, J = 11.5 Hz, 1H, CH2 of Bn), 4.36 (m, 2H,
H-10, H-16), 4.22 (m, 2H, CH2 of Bn, H-5a00), 3.95 (d, J = 9.8 Hz, 1H,
H-6a0), 4.80 (t, J = 9.2 Hz, 1H, H-40), 3.75 (d, J = 2.3 Hz, 2H, CH2 of
NPAc), 3.61 (m, 1H, H-6b0), 3.53 (m, 2H, H-50, H-30), 3.44 (m, 3H,
H-3, H-26a, H-5b00), 3.35 (m, 1H, H-26b), 2.02 (s, 3H, CH3 of Ac),
2.01–1.91(m, 3H), 1.84–1.75 (m, 4H), 1.71–1.40 (m, 12H), 1.23–
1.12 (m, 4H), 0.94 (d, J = 7.0 Hz, 3H, H-21), 0.88 (m, 2H), 0.82 (s,
3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27), 0.73 (s, 3H, H-18), 0.64
(m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.9, 168.1, 165.5, 165.5,
165.1 (OC@O), 133.4, 133.2, 133.1, 132.8, 129.8, 129.7, 129.0–
127.1, 125.0, 109.2 (C-22), 100.4 (C-100), 98.5 (C-10), 83.3 (C-30),
80.6 (C-16), 77.6 (C-3), 74.6 (C-40), 74.6 (CH2 of Bn), 74.38 (C-50),
74.38 (C-20), 73.34 (CH2 of Bn), 72.3 (C-6), 71.6 (C-300), 71.5 (C-
200), 69.7 (C-400), 69.5 (C-60), 66.8 (C-26), 62.2 (C-500), 62.1, 55.9,
53.7, 48.4, 48.3, 45.6, 40.5, 39.8, 39.0 (CH2 of NPAc), 37.8, 37.0,
36.7, 33.6, 31.6, 31.3, 30.3, 28.8, 28.7, 21.3 (CH3-Ac), 20.8, 17.1
(C-27), 16.3 (C-18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
+11.9 (c 0.03, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.01 (d,
J = 7.3 Hz, 2H, H-Ar), 7.91 (d, J = 8.3 Hz, 2H, H-Ar), 7.82 (d,
J = 7.4 Hz, 2H, H-Ar), 7.56–7.03 (m, 23H, H-Ar), 5.71 (t, J = 8.2 Hz,
1H, H-200), 5.53 (s, 1H, H-400), 5.36 (d, J = 10.0 Hz, 1H, H-300), 4.97
(t, J = 8.8 Hz, 1H, H-20), 4.95 (d, J = 9.9 Hz, 1H, CH2 of Bn), 4.77 (d,
J = 7.6 Hz, 1H, H-100), 4.71 (d, J = 10.0 Hz, 1H, CH2 of Bn), 4.61–
4.60 (m, 1H, H-6), 4.58 (d, J = 12.1 Hz, 1H, CH2 of Bn), 4.49 (d,
J = 7.7 Hz, 1H, H-10), 4.34 (m, 1H, H-16), 4.32 (d, J = 12.2 Hz, 1H,
CH2 of Bn), 4.10 (t, J = 9.1 Hz, 1H, H-40), 3.95 (d, J = 12.8 Hz, 1H,
H-5a00), 3.75 (t, J = 8.8 Hz, 1H, H-30), 3.60 (d, J = 10.7 Hz, 1H, H-
6a0), 3.52 (d, J = 10.7 Hz, 1H, H-6b0), 3.46–3.44 (m, 4H, H-3, H-5b00,
CH2 of NPAc), 3.34–3.32 (m, 2H, H-26a, H-26b), 3.26 (d,
J = 10.9 Hz, 1H, H-50), 1.96 (s, 3H, CH3 of Ac), 1.90–1.57 (m, 12H),
1.33–1.02 (m, 10H), 0.86 (m, 3H), 0.93 (d, J = 6.8 Hz, 3H, H3–21),
0.83 (s, 3H, H-19), 0.77 (d, J = 5.9 Hz, 3H, H-27), 0.73 (s, 3H, H-
18), 0.62–0.60 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.1, 165.6,
165.6, 165.0, 162.8 (OC@O), 146.7, 138.1, 138.0, 133.4, 133.4,
133.1, 129.7–127.5, 109.3 (C-22), 100.9 (C-100), 98.6 (C-10), 80.7
(C-16), 80.4 (C-30), 78.0 (C-3), 77.0 (C-40), 76.8 (C-20), 74.5 (C-50),
74.4, 73.4 (CH2 of Bn), 72.3 (C-6), 71.3 (C-300), 70.5 (C-200), 69.0
(C-400), 67.7 (C-60), 66.9 (C-26), 63.8 (C-500), 62.1, 55.9, 53.7, 48.4,
41.5, 40.5, 39.8 (CH2 of NPAc), 37.8, 37.1, 36.7, 33.6, 31.6, 31.3,
30.3, 29.6, 28.8, 28.7, 27.9, 21.2 (CH3 of Ac), 20.8, 17.1 (C-27),
16.3 (C-18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for
C
83H93NO20Na [M+Na]+: 1446.6183, found: 1446.6070.
4.3.27. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-b-
xylopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
glucopyranoside] 6 -acetate (43)
D-
C
83H93NO20Na [M+Na]+: 1446.6183, found: 1446.6182.
D-
a
4.3.25. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-b-
fucopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
glucopyranoside] 6 -acetate (41)
L
-
According to the general procedure for glycosylation, treatment
D
-
of 29 (90 mg, 0.09 mmol) and 18 (84 mg, 0.14 mmol) in CH2Cl2
a
afforded 43 (74 mg, 57%) as a white solid: mp 116–120 °C; ½a D25
ꢂ
According to the general procedure for glycosylation, treatment
ꢁ18.6 (c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.97–7.85 (m,
6H, H-Ar), 7.54–7.18 (m, 23H, H-Ar), 5.65 (d, J = 6.5 Hz, 1H, H-300),
5.37–5.34 (m, 1H, H-200), 5.24–5.22 (m, 1H, H-400), 4.88 (dd,
J = 6.6, 9.5 Hz, 1H, H-20), 4.83 (d, 1H, J = 10.8 Hz, 1H, CH2 of Bn),
4.81 (d, J = 6.7 Hz, 1H, H-100), 4.62–4.60 (m, 1H, H-6), 4.56 (d,
J = 11.3 Hz, 1H, CH2 of Bn), 4.44 (d, J = 11.3 Hz, 1H, CH2 of Bn),
4.36–4.33 (m, 3H, H-16, CH2 of Bn, H-10), 4.17 (dd, J = 11.7,
4.9 Hz, 1H, H-5a00), 3.98 (t, J = 9.3 Hz, 1H, H-40), 3.91 (d,
J = 11.7 Hz, 2H, CH2 of NPAC), 3.60 (dd, J = 10.8, 3.4 Hz, 1H, H-
6a0), 3.55 (t, J = 8.8 Hz, 1H, H-30), 3.50 (d, J = 11.1 Hz, 1H, H-6b0),
3.44–3.41 (m, 1H, H-26a), 3.39–3.37 (m, 1H, H-3), 3.35 (t,
J = 10.8 Hz, 1H, H-26b), 3.24–3.22 (m, 2H, H-5b00, H-50), 1.97 (s,
3H, CH3 of Ac), 1.90–1.82 (m, 3H), 1.76–1.54 (12H), 1.44–1.23
(m, 4H), 1.10–1.08 (m, 4H), 0.93 (d, J = 7.1 Hz, 3H, H-21), 0.87–
0.86 (m, 2H), 0.81 (s, 3H, H-19), 0.77 (d, J = 6.4 Hz, 3H, H-27),
of 29 (90 mg, 0.09 mmol) and 16 (86 mg, 0.14 mmol) in CH2Cl2
afforded 41 (60 mg, 45%) as a white solid: mp 124 °C; ½a D25
ꢁ49.9
ꢂ
(c 0.05, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.07 (d, J = 7.2 Hz,
2H, H-Ar), 7.86 (d, J = 7.3 Hz, 2H, H-Ar), 7.72 (d, J = 7.3 Hz, 2H, H-
Ar), 7.47–7.09 (m, 23H, H-Ar), 5.70 (dd, J = 10.4, 7.8 Hz, 1H, H-200),
5.62 (d, J = 3.5 Hz, 1H, H-400), 5.45 (dd, J = 10.4, 3.5 Hz, 1H, H-300),
5.14 (d, J = 7.7 Hz, 1H, H-100), 4.88 (dd, J = 9.4, 9.4 Hz, 1H, H-20),
4.65–4.64 (m, 1H, H-6), 4.61 (br s, 2H, CH2 of Bn), 4.54 (d, 1H,
J = 11.7 Hz, CH2 of Bn), 4.39 (d, J = 7.7 Hz, 1H, H-10), 4.36 (dd,
J = 7.2, 15.4 Hz, 1H, H-16), 4.23 (d, J = 11.2 Hz, 1H, CH2 of Bn),
4.10–4.09 (m, 2H, H-6a0, H-6b0), 3.89 (q, J = 6.1 Hz, 1H, H-500), 3.85
(d, J = 9.4 Hz, 1H, H-40), 3.74 (s, 2H, CH2 of NPAC), 3.57–3.56 (m,
1H, H-50), 3.52 (t, J = 9.2 Hz, 1H, H-30), 3.46–3.43 (m, 2H, H-3, H-
26a), 3.35 (t, J = 10.9 Hz, 1H, H-26b), 1.99 (s, 3H, CH3 of Ac),

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
129
0.73 (s, 3H, H-18), 0.62–0.61(m, 1H); 13C NMR (CDCl3, 150 MHz) d
170.8, 167.9, 165.5, 165.4, 164.9 (OC@O), 149.3, 146.6, 138.4,
138.1, 138.0, 137.9, 133.3–127.5, 109.2 (C-22), 100.7 (C-100), 98.8
(C-10), 81.0 (C-30), 80.6 (C-16), 77.8 (C-3), 76.9 (C-40), 74.7 (CH2 of
Bn), 74.6 (C-50), 73.8 (C-20), 73.3 (CH2 of Bn), 72.3 (C-6), 71.9 (C-
300), 71.7 (C-200), 69.7 (C-400), 67.7 (C-60), 66.8 (C-26), 62.3, 62.1 (C-
500), 55.9, 53.7, 48.3, 41.5, 40.5, 39.8, 39.1 (CH2 of NPAc), 37.8,
37.0, 36.7, 33.6, 31.6, 31.3, 30.8, 30.2, 28.8, 28.7, 21.3 (CH3-Ac),
20.8, 17.0 (C-27), 16.3 (C-18), 14.4 (C-21), 13.2 (C-19); HRMS
80.7, 79.2, 77.9, 77.5, 74.5, 74.4, 73.6, 73.4, 73.0, 72.3, 72.2, 72.0,
69.7, 67.6, 66.9, 62.8, 62.1, 56.0, 53.7, 48.4, 41.6, 40.6, 39.8, 39.0
(CH2 of NPAc), 37.8, 37.1, 36.7, 33.6, 31.6, 31.3, 30.3, 28.8, 28.7,
28.2, 21.3, 20.9 (CH3 of Ac), 17.1 (C-27), 16.4 (C-18), 14.5 (C-21),
13.3 (C-19); HRMS (ESI) calcd for
1581.6585, found: 1581.6576.
C
91H99NO22Na [M+Na]+:
4.3.30. Chlorogenin 3b-O-[4-O-(2,3,4,6-tetra-O-benzoyl-b-
galactopyranosyl)-3,6-di-O-benzyl-2-O-(2-(nitro)phenylacetyl-
b- -glucopyranoside] 6 -acetate (46)
According to the general procedure for glycosylation, treatment
D-
(ESI) calcd for
1446.6223.
C
83H93NO20Na [M+Na]+: 1446.6183, found:
D
a
of 29 (90 mg, 0.09 mmol) and 21 (102 mg, 0.14 mmol) in CH2Cl2
4.3.28. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-
mannopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
-glucopyranoside] 6 -acetate (44)
According to the general procedure for glycosylation, treatment
a
-
D
-
afforded 46 (49 mg, 34%) as a white solid: mp 110 °C; ½a D25
ꢂ
+3.1
(c 0.03, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.95 (t, J = 9.1 Hz,
4H, H-Ar), 7.87 (d, J = 7.3 Hz, 2H, H-Ar), 7.74 (t, J = 8.2 Hz, 2H, H-
Ar), 7.57–7.12 (m, 26H, H-Ar), 5.80 (d, J = 3.5 Hz, 1H, H-400), 5.70
(dd, J = 7.9, 10.6 Hz, 1H, H-200), 5.37 (dd, J = 3.7, 10.6 Hz, 1H, H-
300), 5.01 (d, J = 11.1 Hz, 1H, CH2 of Bn), 4.91 (dd, J = 9.0, 7.9 Hz,
1H, H-20), 4.88 (d, J = 7.9 Hz, 1H, H-100), 4.64–4.61 (m, 1H, H-6),
4.62 (d, J = 12.1 Hz, 1H, CH2 of Bn), 4.51 (d, J = 11.6 Hz, 1H, CH2 of
Bn), 4.37–4.30 (m, 3H, H-16, CH2 of Bn, H-10), 4.19–4.16 (m, 2H,
H-6a00, H-6b00), 4.06 (t, J = 9.0 Hz, 1H, H-40), 3.95–3.87 (m, 3H, H-
500, CH2 of NPAC), 3.61 (dd, J = 11.1, 3.7 Hz, 1H, H-6a0), 3.59 (t,
J = 9.5 Hz, 1H, H-30), 3.51 (d, J = 10.0 Hz, 1H, H-6b0), 3.44–3.40 (m,
1H, H-26a), 3.38–3.36 (m, 1H, H-3), 3.35 (t, J = 11.1 Hz, 1H, H-
26b), 3.24–3.15 (m, 1H, H-50), 2.01 (s, 3H, CH3 of Ac), 2.00–1.39
(m, 18H), 1.29–1.05 (m, 5H), 0.93 (d, J = 6.9 Hz, 3H, H-21), 0.86–
0.84 (m, 2H), 0.82 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27),
0.73 (s, 3H, H-18), 0.63–0.60 (m, 1H); 13C NMR (CDCl3, 150 MHz)
d 170.8, 167.9, 165.9, 165.4, 165.3, 165.0 (OC@O), 149.3, 138.8,
138.0, 133.4, 133.4, 133.2, 133.0, 129.9–125.0, 109.2 (C-22),
100.5 (C-100), 98.9 (C-10), 80.65 (C-16), 80.60 (C-30), 77.8 (C-3),
76.9 (C-40), 74.5 (C-50), 74.2 (CH2 of Bn), 73.6 (C-20), 73.4 (CH2 of
Bn), 72.3 (C-6), 71.6 (C-300), 71.1 (C-500), 70.3 (C-200), 67.9 (C-400),
67.6 (C-60), 66.8 (C-26), 62.1, 61.5 (C-600), 55.9, 53.7, 48.4, 41.6,
40.5, 39.8, 39.0 (CH2 of NPAc), 37.8, 37.1, 36.7, 33.6, 31.6, 31.3,
30.3, 28.8, 28.7, 28.2, 21.3 (CH3 of Ac), 20.8, 17.1 (C-27), 16.3 (C-
18), 14.4 (C-21), 13.2 (C-19); HRMS (ESI) calcd for C91H99NO22Na
[M+Na]+: 1581.6585, found: 1581.6489.
D
a
of 29 (90 mg, 0.09 mmol) and 19 (102 mg, 0.14 mmol) in CH2Cl2
afforded 44 (100 mg, 70%) as a white solid: mp 107–110 °C; ½a D25
ꢂ
ꢁ29.1 (c 0.06, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.06–7.01 (m,
34H, H-Ar), 6.14 (t, J = 10.2 Hz, 1H, H-400), 5.99–5.98 (m, 1H, H-
300), 5.57–5.56 (m, 1H, H-200), 5.50 (br s, 1H, H-100), 4.99 (t,
J = 8.4 Hz, 1H, H-20), 4.69 (m, 1H, H-6), 4.63–4.62 (m, 3H, H-500,
CH2 of Bn), 4.60–4.53 (m, 2H, CH2 of Bn), 4.50 (d, J = 7.8 Hz, 1H,
H-10), 4.44 (m, 1H, H-6a00), 4.37–4.36 (m, 1H, H-16), 4.24–4.20
(m, 1H, H-6b00), 3.96–3.89 (m, 3H, H-40, CH2 of NPAc), 3.85–3.78
(m, 3H, H-6a0, H-6b0, H-30), 3.64–3.61 (m, 1H, H-50), 3.54–3.50
(m, 1H, H-3), 3.46–3.44 (m, 1H, H-26a), 3.36–3.31 (m, 1H, H-
26b), 2.02 (s, 3H, CH3 of Ac), 1.93–1.84 (m, 3H), 1.78–1.41 (m,
15H), 1.27 (m, 3H), 1.21–1.10 (m, 2H), 0.95 (d, J = 7.0 Hz, 3H, H-
21), 0.89–0.88 (m, 2H), 0.86 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H,
H-27), 0.75 (s, 3H, H-18), 0.68–0.66 (m, 1H); 13C NMR (CDCl3,
150 MHz) d 171.1, 170.9, 170.7, 166.0, 165.6, 165.2 (OC@O),
149.2, 146.5, 138.0, 137.5, 137.0, 133.4–132.9, 130.0–127.2,
125.1, 109.2 (C-22), 98.8 (C-10), 97.8 (C-100), 82.9 (C-30), 80.6 (C-
16), 74.9 (C-40), 74.5 (C-50), 74.4 (C-20), 73.5, 73.5 (CH2 of Bn),
72.3 (C-6), 70.2 (C-200), 69.3 (C-60), 68.9 (C-500), 66.87 (C-26),
66.87 (C-400), 66.5 (C-300), 62.6 (C-600), 62.1, 60.3, 55.9, 53.7, 53.4,
41.6, 40.5, 39.8, 39.2 (CH2 of NPAc), 37.8, 37.1, 36.7, 33.6, 31.6,
31.3, 30.3, 29.6, 28.7, 21.3 (CH3 of Ac), 20.9, 17.1 (C-27), 16.4 (C-
18), 14.4 (C-21), 13.3 (C-19); HRMS (ESI) calcd for C91H99NO22Na
[M+Na]+: 1581.6585, found: 1581.6509.
4.3.31. Chlorogenin 3b-O-{4-O-[2,3,6-tri-O-benzoyl-4-(2,3,4,6-
tetra-O-benzoyl-b-
di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
-acetate (47)
According to the general procedure for glycosylation, treatment
D
-galactopyranosyl)-b-
D
-glucopyranosyl]-3,6-
4.3.29. Chlorogenin 3b-O-[4-O-(2,3,4,6-tetra-O-benzoyl-
glucopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-b-
glucopyranoside] 6 -acetate (45)
a
-
D
-
D-glucopyranoside}
D-
6a
a
According to the general procedure for glycosylation, treatment
of 29 (90 mg, 0.09 mmol) and 22 (167 mg, 0.14 mmol) in CH2Cl2
of 29 (90 mg, 0.09 mmol) and 20 (102 mg, 0.14 mmol) in CH2Cl2
afforded 47 (98 mg, 53%) as a white solid: mp 123 °C; ½a D25
ꢂ
+6.8
afforded 45 (92 mg, 62%) as a white solid: mp 102 °C; ½a D25
ꢂ
ꢁ17.5
(c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.84–8.02 (m, 12H,
H-Ar), 7.70 (d, J = 7.5 Hz, 2H, H-Ar), 7.62–7.00 (m, 35H, H-Ar),
5.67 (m, 2H, H-4000, H-2000), 5.56 (t, J = 9.7 Hz, 1H, H-300), 5.38 (dd,
J = 8.2, 9.8 Hz, 1H, H-200), 5.29 (m, 1H, H-3000), 4.82 (m, 2H, CH2 of
Bn, H-20), 4.71 (d, J = 8.1 Hz, 1H, H-100), 4.69 (d, J = 7.9 Hz, 1H, H-
1000), 4.61 (m, 1H, H-6), 4.57 (d, J = 12.2 Hz, 1H, CH2 of Bn), 4.34
(d, 2H, H-16, CH2 of Bn), 4.30–4.26 (m, 3H, H-10, H-6a00, CH2 of
Bn), 4.17 (m, 1H, H-6b00), 4.08 (d, J = 9.5 Hz, 1H, H-400), 3.91 (t,
J = 9.2 Hz, 1H, H-40), 3.77 (m, 3H, H-5000, CH2 of NPAc), 3.67–3.54
(m, 3H, H-6a000, H-6b000, H-6a0), 3.51–3.43 (m, 3H, H-30, H-6b0, H-
26a), 3.37–3.29 (m, 3H, H-3, H-26b, H-500), 3.16 (m, 1H, H-50),
1.99 (s, 3H, CH3 of Ac), 1.92–1.52 (m, 13H), 1.47–1.19 (m, 6H),
1.08–1.06 (m, 3H), 0.93 (d, J = 7.0 Hz, 3H, H-21), 0.91–0.81 (m,
3H), 0.80 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27), 0.72 (s, 3H,
H-18), 0.61–0.60 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.80,
167.95, 165.71, 165.5, 165.3, 165.2, 165.2, 165.0, 164.8 (OC@O),
149.1, 138.7, 137.8, 137.8, 133.4, 133.3, 133.27, 133.22, 133.08,
133.01, 132.7, 130.8, 129.9–127.7, 127.0, 126.9, 125.2, 124.9,
109.2 (C-22), 100.7 (C-1000), 100.4 (C-100), 98.7 (C-10), 80.7 (C-30),
(c 0.04, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 7.92–7.77 (m, 6H,
H-Ar), 7.48–7.47 (m, 23H, H-Ar), 7.19–7.16 (m, 5H, H-Ar), 5.68 (t,
J = 9.6 Hz, 1H, H-200), 5.50 (t, J = 9.6 Hz, 1H, H-300), 5.46 (t,
J = 9.6 Hz, 1H, H-400), 4.93 (d, J = 12.0 Hz, 1H, CH2 of Bn), 4.88–
4.86 (m, 2H, H-100, CH2 of Bn), 4.64–4.62 (m, 2H, H-6, CH2 of Bn),
4.42–4.40 (m, 2H, CH2 of Bn, H-10), 4.35–4.30 (m, 3H, H-6a0, H-
6b0, H-16), 4.09 (dd, J = 6.0, 12.0 Hz, 1H, H-6a00), 4.01 (t,
J = 12.0 Hz, 1H, H-6b00), 3.80 (br s, 2H, CH2 of NPAc), 3.75–3.74
(m, 1H, H-26a), 3.61–3.59 (m, 1H, H-26b), 3.55 (t, J = 9.1 Hz, 1H,
H-30), 3.45–3.33 (m, 3H, H-50, H-3, H-500), 3.21 (br d, J = 10.9 Hz,
1H, H-20), 2.00 (s, 3H, CH3-Ac), 1.98–1.95 (m, 1H), 1.84–1.41 (m,
16H), 1.26–1.06 (m, 7H), 0.94 (d, J = 6.9 Hz, 3H, H-21), 0.87 (m,
1H), 0.84 (s, 3H, H-19), 0.77 (d, J = 6.3 Hz, 3H, H-27), 0.76 (s, 3H,
H-18), 0.66 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.9, 168.1,
166.0, 165.7, 165.1, 164.9, 135.8, 133.4, 133.4, 133.2, 133.1,
133.1, 132.8, 130.0, 129.9, 129.8, 129.7, 129.7, 129.5, 129.0,
128.8, 128.6, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.1,
128.0, 127.2, 125.0, 109.3 (C-22), 100.6 (C-100), 98.8 (C-10), 80.8,

130
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
80.6 (C-16), 77.7 (C-3), 77.3 (C-40), 75.6 (C-400), 74.4 (C-50), 74.1
(CH2 of Bn), 73.5 (C-20), 73.3 (CH2 of Bn), 72.8 (C-300), 72.7 (C-500),
72.3 (C-6), 72.1 (C-200), 71.7 (C-3000), 71.2 (C-5000), 69.7 (C-2000), 67.5
(C-60), 67.4 (C-4000), 66.8 (C-26), 62.3 (C-600), 62.1, 60.9 (C-6000),
55.9, 53.7, 48.3, 41.5, 40.5, 39.8, 38.7 (CH2 of NPAc), 37.8, 37.0,
36.7, 33.63, 31.65, 31.3, 30.2, 29.6, 28.8, 28.1, 21.3 (CH3 of Ac),
20.8, 17.1 (C-27), 16.3 (C-18), 14.4 (C-21), 14.0 (C-19); HRMS
163.3 (OC@O), 138.0–132.9, 129.9–126.0, 109.2 (C-22), 98.8 (C-
10), 98.0 (C-100), 97.1 (C-1000), 84.2 (C-30), 80.6 (C-16), 76.8 (C-20),
76.6 (C-3), 74.9 (C-50), 74.6 (C-40), 74.5 (CH2 of Bn), 73.0 (CH2 of
Bn), 72.5 (C-6), 71.8 (C-400), 71.5 (C-4000), 71.0 (C-2000), 70.3 (C-200),
70.1 (C-3000), 70.0 (C-300), 68.2 (C-60), 67.1 (C-5000), 66.9 (C-500), 66.8
(C-26), 62.1, 56.0, 53.7, 48.5, 41.6, 40.5, 39.8 (CH2 of NPAc), 37.8,
37.1, 36.7, 33.7, 31.6, 31.3, 30.3, 29.0, 28.7, 27.8, 26.3, 21.3 (CH3
of Ac), 20.9, 17.4 (C-600), 17.3 (C-6000), 17.1 (C-27), 16.4 (C-18),
14.5 (C-21), 13.2 (C-19); HRMS (ESI) calcd for C93H109NO24Na
[M+Na]+: 1647.7265, found: 1647.7298.
(ESI) calcd for
2055.7859.
C
118H121NO30Na [M+Na]+: 2055.7899, found:
4.3.32. Chlorogenin 3b-O-[4-O-(2,3,4-tri-O-benzoyl-
rhamnopyranosyl)-3,6-di-O-benzyl-2-O-(2-nitro)phenylacetyl-
b- -glucopyranoside] 6 -acetate (48)
According to the general procedure for glycosylation, treatment
a-L-
4.3.34. Chlorogenin 3b-O-[2-O-(2,3,4-tri-O-benzoyl-
rhamnopyranosyl)-3,6-di-O-benzyl-4-O-levulinoyl-b-
glucopyranoside] 6 -acetate (50)
a-L-
D-
D
a
a
of 29 (90 mg, 0.09 mmol) and 23 (86 mg, 0.14 mmol) in CH2Cl2
According to the preparation of 29, 48 (1 g, 0.73 mmol) was
treated with hydrazine acetate (101 mg, 1.10 mmol) in CH2Cl2/
methanol (1:1, 4 mL) to afford 50 (726 mg, 78%) as a off-white so-
afforded 48 (125 mg, 95%) as a white solid: mp 131 °C; ½a D25
ꢂ
+9.0
(c 0.06, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.25 (d, J = 8.1 Hz,
1H, H-Ar), 8.03 (d, J = 7.8 Hz, 2H, H-Ar), 8.03–7.09 (m, 26H, H-Ar),
5.67 (d, J = 10.3 Hz, 1H, H-300), 5.53 (m, 2H, H-200, H-400), 5.22 (s,
1H, H-100), 5.11 (t, J = 7.4 Hz, 1H, H-20), 4.80 (d, J = 11.5 Hz, 1H,
CH2 of Bn), 4.71 (d, J = 11.4 Hz, 1H, CH2 of Bn), 4.68 (d, J = 7.2 Hz,
1H, H-10), 4.65 (m, 1H, H-6), 4.56 (dd, J = 4.5, 12 Hz, 2H, CH2 of
Bn), 4.36 (dd, J = 7.2, 15.4 Hz, 1H, H-16), 4.17–4.15 (m, 2H, H-40,
H-500), 3.80–3.74 (m, 3H, H-30, H-6a0, H-6b0), 3.55–3.54 (m, 2H, H-
50, H-3), 3.45–3.43 (m, 1H, H-26a), 3.37 (t, J = 10.9 Hz, 1H, H-
26b), 2.03 (s, 3H, CH3-Ac), 2.01–1.10 (m, 23H), 0.94 (d, J = 6.7 Hz,
3H, H-21), 0.89 (m, 2H), 0.86 (s, 3H, H-19), 0.80 (d, J = 6.1 Hz, 3H,
CH3-600), 0.77 (d, J = 6.1 Hz, 3H, H-27), 0.74 (s, 3H, H-18), 0.67–
0.66 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.6, 165.7, 165.6,
165.6, 162.9 (OC@O), 146.5, 137.9, 137.6, 133.5, 133.4, 133.2,
133.1, 132.7, 131.0, 130.2–126.7, 125.8, 109.2 (C-22), 98.6 (C-100),
96.9 (C-10), 80.6 (C-16), 80.4 (C-30), 78.0 (C-3), 77.2 (C-20), 75.1
(C-50), 74.2 (C-40), 73.6 (CH2 of Bn), 73.0 (CH2 of Bn), 72.3 (C-6),
71.5 (C-400), 71.0 (C-200), 69.9 (C-300), 68.2 (C-60), 67.1 (C-500), 66.8
(C-26), 62.1, 55.9, 53.7, 48.5, 41.5, 40.5, 39.8 (CH2 of NPAc), 37.8,
37.1, 36.7, 33.6, 31.6, 31.3, 30.8, 28.9, 28.7, 28.1, 21.3 (CH3 of Ac),
20.8, 17.0 (C-600), 16.9 (C-27), 16.3 (C-18), 14.4 (C-21), 13.3 (C-
19); HRMS (ESI) calcd for C84H95NO20Na [M+Na]+: 1460.6340,
found: 1460.6469.
lid: mp 133 °C; ½a D25
ꢂ
+51.9 (c 0.1, CH2Cl2); 1H NMR (CDCl3,
600 MHz) d 7.93 (d, J = 7.6 Hz, 2H, H-Ar), 7.84 (d, J = 7.7 Hz, 2H,
H-Ar), 7.71 (d, J = 7.7 Hz, 2H, H-Ar), 7.51–7.01 (m, 19H, H-Ar),
5.69 (s, 1H, H-300), 5.67 (s, 1H, H-200), 5.54 (t, J = 9.8 Hz, 1H, H-400),
5.37 (s, 1H, H-100), 4.86 (d, 1H, J = 11.3 Hz, CH2 of Bn), 4.74 (d,
J = 11.4 Hz, 1H, CH2 of Bn), 4.62–4.60 (m, 1H, H-500), 4.56–4.50
(m, 1H, H-6), 4.50 (s, 1H, H-10), 4.49–4.40 (m, 2H, CH2 of Bn),
4.28 (q, J = 7.4 Hz, 1H, H-16), 3.65–3.60 (m, 2H, H-6a0, H-6b0),
3.63–3.61 (m, 2H, H-3, H-20), 3.55–3.52 (m, 2H, H-30, H-40), 3.38–
3.37 (m, 1H, H-50), 3.36–3.34 (m, 1H, H-26a), 3.26 (t, J = 10.9 Hz,
1H, H-26b), 1.95 (s, 3H, CH3 of Ac), 1.88–1.34 (m, 18H), 1.18–
0.82 (m, 6H), 1.22 (d, J = 6.0 Hz, 3H, H-600), 0.86 (d, J = 6.8 Hz, 3H,
H-21), 0.78 (m, 1H), 0.69 (d, J = 6.1 Hz, 3H, H-27), 0.63 (s, 3H, H-
19), 0.60 (s, 3H, H-18), 0.57 (m, 1H); 13C NMR (CDCl3, 150 MHz) d
170.8, 166.0, 165.5, 165.4 (OC@O), 138.3, 137.6, 133.3, 133.2,
133.0, 129.8–127.7, 109.2 (C-22), 98.6 (C-10), 97.8 (C-100), 85.9 (C-
30) 80.6 (C-16), 76.7 (C-3), 76.5 (C-20), 75.5, 73.6 (CH2 of Bn), 72.9
(C-40), 72.4 (C-6), 71.8 (C-400), 70.6 (C-200), 70.6 (C-60), 70.0 (C-300),
66.8 (C-26), 66.7 (C-500), 62.1, 55.9, 53.7, 48.3, 41.5, 40.5, 39.7,
37.7, 37.1, 36.7, 33.6, 31.6, 31.3, 30.2, 29.1, 28.7, 28.0, 21.3 (CH3
of Ac), 20.8, 17.4 (C-600), 17.1 (C-27), 16.3 (C-19), 14.4 (C-21),
13.1 (C-18); HRMS (ESI) calcd for
1297.6070, found: 1297.6074.
C
76H90O17Na [M+Na]+:
4.3.33. Chlorogenin 3b-O-{3,6-di-O-benzyl-4-O-[4-O-(2,3,4-tri-
O-benzoyl-
rhamnopyranosyl]-2-O-(2-nitro) phenylacetyl-b-
glucopyranoside} 6 -acetate (49)
a
-
L
-rhamnopyranosyl) 2,3-di-O-isopropylidene-
a-
L-
4.3.35. Chlorogenin 3b-O-[2,4-di-O-(2,3,4-tri-O-benzoyl-
a
-
L
-
a
D-
rhamnopyranosyl)-3,6-di-O-benzyl-b-
D-glucopyranoside] 6
-
a
acetate (51)
According to the general procedure for glycosylation, treatment
According to the general procedure for glycosylation, treatment
of 29 (90 mg, 0.09 mmol) and 24 (111 mg, 0.14 mmol) in CH2Cl2
of 50 (90 mg, 0.07 mmol) and 23 (66 mg, 0.11 mmol) in CH2Cl2
afforded 49 (68 mg, 46%) as a white solid: mp 136–140 °C; ½a D25
ꢂ
afforded 51 (102 mg, 83%) as a white solid: mp 123 °C; ½a D25
ꢂ
+18.1 (c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.27 (d,
J = 7.2 Hz, 1H, H-Ar), 8.08 (d, J = 7.0 Hz, 2H, H-Ar), 7.96 (d,
J = 7.0 Hz, 2H, H-Ar), 7.89 (d, J = 7.4 Hz, 1H, H-Ar), 7.80 (d,
J = 7.1 Hz, 2H, H-Ar), 7.68 (t, J = 7.2 Hz, 2H, H-Ar), 7.60–7.14 (m,
19H, H-Ar), 5.73 (dd, J = 3.8, 10.9 Hz, 1H, H-300), 5.70 (dd, J = 10.0,
4.4 Hz, 1H, H-3000), 5.66 (s, 1H, H-200), 5.61 (s, 1H, H-2000), 5.56 (t,
J = 10.4 Hz, 1H, H-400), 5.54 (t, J = 10.4 Hz, 1H, H-4000), 5.35 (s, 1H,
H-100), 5.28 (s, 1H, H-1000), 5.08 (d, J = 12.0 Hz, 1H, CH2 of Bn), 5.01
(d, J = 12.0 Hz, 1H, CH2 of Bn), 4.70 (m, 1H, H-500), 4.66 (m, 1H, H-
6), 4.65 (d, J = 7.6 Hz, 1H, H-10), 4.63 (d, J = 12.4 Hz, 1H, CH2 of
Bn), 4.58 (d, J = 12.0 Hz, 1H, CH2 of Bn), 4.37 (q, J = 7.2 Hz, 1H, H-
16), 4.32 (m, 1H, H-5000), 4.09 (t, J = 8.8 Hz, 1H, H-40), 3.89–3.81
(m, 4H, H-20, H-30, H-6a0, H-6b0), 3.73 (m, 1H, H-3), 3.55 (d,
J = 9.6 Hz, 1H, H-50), 3.45 (m, 1H, H-26a), 3.33 (t, J = 11.2 Hz, 1H,
H-26b), 2.05 (s, 3H, CH3 of Ac), 1.95–1.43 (m, 22H), 1.30 (d,
J = 6.0 Hz, 3H, H-600), 1.14–1.13 (m, 3H), 0.95 (d, J = 5.6 Hz, 3H, H-
6000), 0.94 (d, J = 6.4 Hz, 3H, H-21), 0.77 (d, J = 7.2 Hz, 3H, H-27),
0.72 (s, 3H, H-19), 0.71 (s, 3H, H-18), 0.66–0.65 (m, 1H); 13C
NMR (CDCl3, 150 MHz) d 170.8, 165.9, 165.7, 165.6, 165.5, 164.9,
+42.5 (c 0.07, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.04 (d,
J = 8.1 Hz, 2H, H-Ar), 7.91 (d, J = 8.1 Hz, 2H, H-Ar), 7.81 (t,
J = 9.1 Hz, 4H, H-Ar), 7.74 (d, J = 8.1 Hz, 2H, H-Ar), 7.68 (t,
J = 8.2 Hz, 2H, H-Ar), 7.58–6.76 (m, 28H, H-Ar), 5.73 (dd, J = 10.9,
3.8 Hz, 1H, H-300), 5.70 (dd, J = 4.4, 10.0 Hz, 1H, H-3000), 5.66 (s, 1H,
H-200), 5.61 (s, 1H, H-2000), 5.56 (t, J = 10.4 Hz, 1H, H-400), 5.54 (t,
J = 10.4 Hz, 1H, H-4000), 5.35 (s, 1H, H-100), 5.28 (s, 1H, H-1000), 5.08
(d, J = 12.0 Hz, 1H, CH2 of Bn), 5.01 (d, J = 12.0 Hz, 1H, CH2 of Bn),
4.70 (m, 1H, H-500), 4.66–4.65 (m, 1H, H-6), 4.65 (d, J = 7.6 Hz, 1H,
H-10), 4.63 (d, J = 12.4 Hz, 1H, CH2 of Bn), 4.58 (d, J = 12.0 Hz, 1H,
CH2 of Bn), 4.37 (q, J = 7.2 Hz, 1H, H-16), 4.32 (m, 1H, H-5000), 4.09
(t, J = 8.8 Hz, 1H, H-40), 3.89–3.81 (m, 4H, H-20, H-30, H-6a0, H-
6b0), 3.73–3.72 (m, 1H, H-3), 3.55 (d, J = 9.6 Hz, 1H, H-50), 3.45–
3.44 (m, 1H, H-26a), 3.33 (t, J = 11.2 Hz, 1H, H-26b), 2.08–2.06
(m, 1H), 2.05 (s, 3H, CH3 of Ac), 1.93–1.91 (m, 2H), 1.83–1.82 (m,
1H), 1.77–1.39 (m, 15H), 1.30 (d, J = 6.0 Hz, 3H, H-600), 1.28–1.00
(m, 5H), 0.95 (d, J = 5.6 Hz, 3H, H-6000), 0.94 (d, J = 6.4 Hz, 3H, H-
21), 0.88 (m, 1H), 0.77 (d, J = 7.2 Hz, 3H, H-27), 0.72 (s, 3H, H-19),
0.71 (s, 3H, H-18), 0.68–0.67 (m, 1H); 13C NMR (CDCl3, 150 MHz)

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
131
d 170.8, 165.9, 165.7, 165.6, 165.5, 164.9, 163.3 (OC@O), 138.0–
132.9, 129.9–126.0, 109.2 (C-22), 98.8 (C-10), 98.0 (C-100), 97.1 (C-
1000), 84.2 (C-30), 80.6 (C-16), 76.8 (C-20), 76.6 (C-3), 74.9 (C-50),
74.6 (C-40), 74.5 (CH2 of Bn), 73.0 (CH2 of Bn), 72.5 (C-6), 71.8 (C-
400), 71.5 (C-4000), 71.0 (C-2000), 70.3 (C-200), 70.1 (C-3000), 70.0 (C-300),
68.2 (C-60), 67.1 (C-5000), 66.9 (C-500), 66.8 (C-26), 62.1, 55.9, 53.7,
48.3, 41.6, 40.5, 39.7, 37.7, 37.2, 36.7, 33.69, 31.68, 31.3, 30.2,
29.1, 28.7, 28.0, 21.3 (CH3 of Ac), 20.8, 17.4 (C-600), 17.3 (C-6000),
17.16 (C-27), 16.43 (C-18), 14.52 (C-21), 13.20 (C-19); HRMS
6), 75.8 (C-20), 72.22 (C-30), 72.2 (C-40), 68.9 (C-3), 67.3 (C-26),
64.9 (C-20), 63.4, 63.3 (C-60), 56.8, 54.6, 52.6, 43.1, 42.4, 41.2,
40.5, 38.1, 37.0, 34.7, 32.6, 32.2, 31.0, 30.4, 29.9, 29.7, 21.7, 17.7
(C-27), 17.0 (C-19), 15.4 (C-21), 14.0 (C-18); HRMS (ESI) calcd for
C
33H54O9 [M+Na]+: 617.3661, found: 617.3692.
4.3.38. Chlorogenin 3b-O-[2-O-(b-L-arabinopyranosyl)-b-D-
glucopyranoside] (54)
By the similar procedure of synthesis of 53, treatment of com-
pound 30 (110 mg, 0.08 mmol) afforded 54 (24 mg, 41%) as a white
(ESI) calcd for
1756.7499.
C
103H112O24Na [M+Na]+: 1756.7470, found:
solid: mp 267 °C; ½a D25
ꢂ
ꢁ15.4 (c 0.06, MeOH); 1H NMR (pyridine-,
600 MHz) d 5.41 (d, J = 6.1 Hz, 1H, H-100), 5.11 (d, J = 6.1 Hz, 1H,
H-10), 4.63 (t, J = 6.4 Hz, 1H, H-200), 4.56–4.51 (m, 3H, H-16, H-5a00,
H-6a0), 4.37–4.37 (m, 2H, H-400, H-6b0), 4.28–4.24 (m, 3H, H-300, H-
30, H-40), 4.16 (d, J = 8.4 Hz, 1H, H-20), 4.07–4.06 (m, 1H, H-6),
3.88 (dd, J = 12.1, 2.2 Hz, 1H, H-5b00), 3.82–3.81 (m, 1H, H-50),
3.63–3.61 (m, 1H, H-3), 3.60–3.58 (m, 1H, H-26a), 3.51 (t,
J = 10.7 Hz, 1H, H-26b), 3.18 (d, J = 12.6 Hz, 1H, OH), 2.25–2.10
(m, 3H), 1.98–1.56 (m, 14H), 1.47–1.22 (m, 6H), 1.16 (d,
J = 7.0 Hz, 4H, H-21), 1.10–0.90 (m, 2H), 0.86 (s, 3H, H-19), 0.84
(s, 3H, H-18), 0.71 (d, J = 5.8 Hz, 3H, H-27), 0.65–0.64 (m, 1H);
13C NMR (pyridine-d5, 150 MHz) d 109.7 (C-22), 106.1 (C-100),
100.7 (C-10), 83.1 (C-20), 81.5 (C-16), 78.72 (C-300), 78.71 (C-50),
78.6 (C-6), 74.5 (C-30), 73.5 (C-200), 71.8 (C-40), 69.1 (C-400), 68.8
(C-3), 67.3 (C-26), 66.6 (C-500), 63.4, 63.0 (C-60), 56.8, 54.6, 52.7,
43.2, 42.4, 41.2, 40.5, 38.1, 37.0, 34.7, 32.6, 32.2, 31.0, 30.3, 29.7,
29.6, 21.7, 19.7 (C-27), 17.7 (C-19), 17.0 (C-21), 15.5 (C-18); HRMS
(ESI) calcd for C38H62O13Na [M+Na]+: 749.4083, found: 749.4051.
4.3.36. Chlorogenin 3b-O-{3,6-di-O-benzyl-2-O-(2,3,4-tri-O-
benzoyl- -rhamnopyranosyl)-4-O-[4-O-(2,3,4-tri-O-benzoyl-
-Lrhamnopyranosyl)-2,3-di-O-isopropylidene-
rhamnopyranosyl]-b- -glucopyranoside] 6 -acetate (52)
a
-L
a
a-L-
D
a
According to the general procedure for glycosylation, treatment
of 50 (90 mg, 0.07 mmol) and 24 (85 mg, 0.11 mmol) in CH2Cl2
afforded 52 (83 mg, 0.04 mmol, 61%) as a white solid: mp 118 °C;
½
a 2D5 +35.3 (c 0.2, CH2Cl2); 1H NMR (CDCl3, 600 MHz) d 8.08 (d,
ꢂ
J = 7.6 Hz, 2H, H-Ar), 7.91 (m, 6H, H-Ar), 7.77 (t, J = 8.7 Hz, 4H, H-
Ar), 7.60–6.97 (m, 28H, H-Ar), 5.74 (m, 1H, H-30000), 5.61 (s, 1H, H-
20000), 5.57–5.64 (m, 4H, H-200, H-400, H-40000, H-300), 5.45 (s, 1H, H-
10000), 5.43 (s, 1H, H-100), 5.19 (s, 1H, H-1000), 4.93 (s, 2H, CH2 of Bn),
4.71–4.70 (m, 1H, H-50000), 4.66–4.65 (m, 1H, H-6), 4.63 (d,
J = 7.8 Hz, 1H, H-10), 4.62 (s, 2H, CH2 of Bn), 4.38 (dd, J = 7.3,
14.9 Hz, 1H, H-16), 4.15–4.13 (m, 2H, H-4000, H-2000), 3.98–3.95 (m,
2H, H-500, H-40), 3.83–3.80 (m, 2H, H-20, H-5000), 3.77–3.68 (m, 4H,
H-6a0, H-6b0, H-30, H-3), 3.53–3.45 (m, 3H, H-50, H-3000, H-26a),
3.36 (t, J = 10.9 Hz, 1H, H-26b), 2.19–1.70 (m, 13H), 1.68 (s, 3H,
C(CH3)2), 1.60–1.59 (m, 6H), 1.48 (s, 5H, C(CH3)2), 1.33 (d,
J = 6.2 Hz, 3H, H-60000), 1.27–1.13 (m, 5H), 1.02 (d, J = 6.0 Hz, 3H,
H-6000), 0.95 (d, J = 6.7 Hz, 3H, H-21), 0.87–0.85 (m, 1H), 0.78 (d,
J = 6.2 Hz, 3H, H-27), 0.72 (s, 3H, H-19), 0.70 (s, 3H, H-18), 0.67–
0.66 (m, 1H); 13C NMR (CDCl3, 150 MHz) d 170.7, 165.9, 165.7,
165.5, 165.3, 165.0, 163.3 (OC@O), 137.8, 137.5, 133.3–132.9,
129.9–127.1, 109.5 (C-22), 109.2 (C(CH3)2), 98.7 (C-10), 97.9 (C-
10000), 96.9 (C-1000), 96.5 (C-100), 84.2 (C-3), 80.6 (C-16), 78.0 (C-40000),
78.0 (C-3000), 76.8 (C-20), 76.5 (C-30), 76.1 (C-20000), 75.5 (CH2 of Bn),
74.9 (C-50), 74.4 (C-40), 73.5 (CH2 of Bn), 72.4 (C-6), 71.8 (C-300),
71.8 (C-400), 70.8 (C-4000), 70.4 (C-200), 70.0 (C-2000), 69.8 (C-30000),
69.9 (C-60), 67.0 (C-500), 66.8 (C-50000), 65.1 (C-5000), 62.1, 55.9, 53.7,
48.3, 41.5, 40.5, 39.7 (CH3), 37.7, 37.1, 36.7, 33.6, 31.6, 31.3, 30.2,
29.1, 28.7, 28.0, 27.8, 26.2, 21.2 (CH3 of Ac), 20.8 (CH3), 17.7 (C-
6000), 17.5 (C-600), 17.4 (C-60000), 17.0 (C-27), 16.3 (C-19), 14.4 (C-
21), 13.1 (C-18); HRMS (ESI) calcd for C112H126O28Na [M+Na]+:
1942.8362, found: 1942.8255.
4.3.39. Chlorogenin 3b-O-[2-O-(b-L-fucopyranosyl)-b-D-
glucopyranoside] (55)
By the similar procedure of synthesis of 53, treatment of com-
pound 31 (111 mg, 0.08 mmol) afforded 55 (30 mg, 50%) as a white
solid: mp 259 °C; ½a D25
ꢂ
ꢁ47.2 (c 0.04, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.20 (d, J = 7.8 Hz, 1H, H-100), 5.06 (d, J = 7.7 Hz, 1H, H-
10), 4.55–4.51 (m, 2H, H-16, H-6a0), 4.39–4.36 (m, 2H, H-200, H-6b0),
4.26 (t, J = 9.0 Hz, 1H, H-40), 4.16–4.01 (m, 5H, H-30, H-300, H-20, H-6,
H-400), 3.85–3.78 (m, 2H, H-500, H-50), 3.66–3.65 (m, 1H, H-3), 3.61–
3.60 (m, 1H, H-26a), 3.51 (t, J = 10.7 Hz, 1H, H-26b), 2.26–2.24 (m,
1H), 2.13–2.10 (m, 2H), 1.98–1.54 (m, 15H), 1.51 (d, J = 6.4 Hz, 3H,
H-600), 1.45–1.23 (m, 5H), 1.16 (d, J = 7.0 Hz, 3H, H-21), 1.10–0.89
(m, 2H), 0.86 (s, 3H, H-19), 0.85 (s, 3H, H-18), 0.71 (d, J = 5.9 Hz,
3H, H-27), 0.66–0.65 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d
109.6 (C-22), 105.4 (C-100), 101.2 (C-10), 83.3 (C-20), 81.5 (C-16),
78.8 (C-6), 78.6 (C-50), 77.3 (C-30), 75.5 (C-300), 73.1 (C-200), 73.0
(C-400), 72.2 (C-500), 71.9 (C-40), 68.9 (C-3), 67.3, 63.4, 67.3 (C-26),
63.1 (C-60), 56.8, 54.6, 52.7, 43.2, 42.4, 41.2, 40.5, 38.1, 37.0, 34.7,
32.6, 32.2, 31.0, 30.5, 29.7, 21.7, 17.7 (C-27), 17.6 (C-600), 17.0 (C-
18), 15.4 (C-21), 14.1 (C-19); HRMS (ESI) calcd for C39H64O13Na
[M+Na]+: 763.4239, found: 763.4214.
4.3.37. Chlorogenin 3b-O-b-D-glucopyranoside (53)
LiOH (58 mg, 1.39 mmol) was added to a solution of 4 (50 mg,
0.05 mmol) in THF/MeOH (3:1, 4 mL). After stirring overnight at
rt, the mixture was concentrated in vacuo and the residue was
purified by column chromatography (CH2Cl2/methanol, 9:1) to give
the crude intermediate. This was then dissolved in CH2Cl2/ethanol
(1:3, 4 mL) and stirred under H2 for 12 h with Pd/C (5 mg, 10%) and.
The residue was filtered, dried in vacuo, and purified by column
4.3.40. Chlorogenin 3b-O-[2-O-(b-L-xylopyranosyl)-b-D-
glucopyranoside] (56)
By the similar procedure of synthesis of 53, treatment of com-
pound 32 (110 mg, 0.08 mmol) afforded 56 (35 mg, 60%) as a white
solid: mp 262 °C; ½a D25
ꢂ
ꢁ25.3 (c 0.01, MeOH); 1H NMR (pyridine-d5,
chromatography (CH2Cl2/methanol, 10:3) to afford
4
(16 mg,
600 MHz) d 5.44 (d, J = 7.0 Hz, 1H, H-100), 5.07 (d, J = 7.8 Hz, 1H, H-
10), 4.54–4.53 (m, 2H, H-16, H-6a0), 4.43 (d, J = 9.5 Hz, 1H, H-5a00),
4.37 (dd, J = 5.2, 11.8 Hz, 1H, H-6b0), 4.26–4.21 (m, 3H, H-30, H-40,
H-400), 4.16–4.11 (m, 2H, H-20, H-300), 4.07–4.02 (m, 2H, H-200, H-
6), 3.81 (m, 1H, H-50), 3.73 (m, 1H, H-5b00), 3.66 (m, 1H, H-3),
3.60 (d, J = 8.8 Hz, 1H, H-26a), 3.51 (t, J = 10.6 Hz, 1H, H-26b),
3.18 (d, J = 12.4 Hz, 1H, OH), 2.28–2.20 (m, 1H), 2.11–2.06 (m,
2H), 1.98–1.93 (m, 1H), 1.87–1.54 (m, 14H), 1.45–1.43 (m, 2H),
1.16 (d, J = 6.8 Hz, 3H, H-21), 1.22–1.09 (m, 4H), 0.88–0.87 (m,
1H), 0.84 (s, 3H, H-19), 0.84 (s, 3H, H-18), 0.71 (d, J = 5.3 Hz, 3H,
58%) as a white-solid: mp 270 °C; ½a D25
ꢂ
ꢁ35.9 (c 0.01, MeOH); 1H
NMR (pyridine-d5, 600 MHz) d 5.10 (d, J = 7.7 Hz, 1H, H-10), 4.56
(m, 2H, H-16, H-6a0), 4.42 (dd, J = 5.1, 11.7 Hz, 1H, H-6b0), 4.27
(m, 2H, H-30, H-40), 4.08 (m, 2H, H-6, H-20), 3.91 (m, 1H, H-50),
3.61 (m, 2H, H-3, H-26a), 3.51 (t, J = 10.4 Hz, 1H, H-26b), 2.28–
1.19 (m, 19H), 1.16 (d, J = 7.0 Hz, 3H, H-21), 1.10–0.89 (m, 6H),
0.86 (s, 3H, H-19), 0.77 (s, 3H, H-18), 0.71 (d, J = 5.2 Hz, 3H, H-
27), 0.66–0.64 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6
(C-22), 102.6 (C-10), 81.5 (C-16), 79.0 (C-50), 78.8 (C-50), 78.0 (C-

132
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
H-27), 0.65–0.64 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.7
(C-22), 105.0 (C-10), 101.4 (C-100), 81.8 (C-300), 81.5 (C-16), 78.8 (C-
6), 78.6 (C-50), 77.7 (C-40), 77.1 (C-20), 75.3 (C-200), 72.0 (C-30), 71.3
(C-400), 69.0 (C-3), 67.3 (C-26), 67.1 (C-500), 63.4, 63.1 (C-60), 56.8,
54.6, 52.7, 43.2, 42.5, 41.2, 40.5, 38.2, 37.0, 34.7, 32.6, 32.3, 31.0,
30.5, 29.7, 29.6, 21.7, 17.8 (C-27), 17.1 (C-19), 15.5 (C-21), 14.1
(C-18); HRMS (ESI) calcd for C38H62O13Na [M+Na]+: 749.4083,
found: 749.4056.
H-30), 4.27–4.23 (m, 3H, H-300, H-26a, H-26b), 4.17–4.14 (m, 2H,
H-20, H-200), 4.06–4.02 (m, 1H, H-500), 3.99–3.96 (m, 1H, H-50),
3.87–3.85 (m, 1H, H-6), 3.66–3.59 (m, 3H, H-6a00, H-6b00), 3.51 (t,
J = 10.8 Hz, 1H), 3.16 (br d, J = 12.6 Hz, 1H), 2.20 (dt, J = 8.1,
4.2 Hz, 1H), 2.15–2.08 (m, 2H), 1.98 (t, J = 6.7 Hz, 1H), 1.83 (dd,
J = 8.4, 6.6 Hz, 1H), 1.76–1.67 (m, 3H), 1.63–1.56 (m, 6H), 1.48–
1.43 (m, 3H), 1.34–1.24 (m, 7H), 1.15 (d, J = 6.7 Hz, 3H, H-21),
1.09–1.06 (m, 1H), 0.84 (s, 3H, H-19), 0.83 (s, 3H, H-18), 0.71 (d,
J = 5.2 Hz, 3H, H-27), 0.65–0.60 (m, 1H); 13C NMR (pyridine-d5,
150 MHz) d 109.7 (C-22), 107.2 (C-100), 102.2 (C-10), 85.6, 81.6 (C-
16), 80.2, 79.3, 78.7, 78.5, 78.3, 77.5, 72.2, 71.8, 69.1, 67.3 (C-26),
63.5, 63.4, 63.1, 56.8, 54.6, 52.6, 43.1, 42.5, 41.3, 40.6, 38.1, 37.1,
34.7, 32.6, 32.3, 31.1, 30.5, 30.4, 30.2, 29.7, 21.8, 17.8, 17.1, 15.5,
14.1; HRMS (ESI) calcd for C39H64O14Na [M+Na]+: 779.4188, found:
779.4203.
4.3.41. Chlorogenin 3b-O-[2-O-(b-D-xylopyranosyl)-b-D-
glucopyranoside] (57)
By the similar procedure of synthesis of 53, treatment of com-
pound 33 (66 mg, 0.05 mmol) afforded 57 (16 mg, 45.3%) as a
white solid: mp 260–265 °C; ½a D25
ꢂ
ꢁ26.8 (c 0.08, MeOH); 1H NMR
(pyridine-d5, 600 MHz) d 5.33 (d, J = 7.1 Hz, 1H, H-100), 5.11 (d,
J = 8.0 Hz, 1H, H-10), 4.56 (dd, J = 7.4, 14.7 Hz, 1H, H-16), 4.50–
4.46 (m, 2H, H-6a0, H-5a00), 4.37 (dd, J = 5.0, 11.8 Hz, 1H, H-6b0),
4.29 (t, J = 8.9 Hz, 1H, H-30), 4.24 (t, J = 9.0 Hz, 1H, H-40), 4.17 (m,
4H, H-400, H-300, H-200, H-20), 4.06–4.04 (m, 1H, H-6), 3.80–3.67 (m,
2H, H-50, H-5b00), 3.64–3.62 (m, 1H, H-3), 3.60–3.58 (m, 1H, H-
26a), 3.51 (t, J = 10.6 Hz, 1H, H-26b), 2.22–2.18 (m, 1H), 2.04–
1.94 (m, 3H), 1.83–1.52 (m, 14H), 1.43–1.39 (m, 2H), 1.19–1.17
(m,3H), 1.16 (d, J = 6.9 Hz, 3H, H-21), 1.07–1.05 (m, 1H), 0.88–
0.86 (m, 1H), 0.85 (s, 3H, H-19), 0.83 (s, 3H, H-18), 0.71 (d,
J = 5.4 Hz, 3H, H-27), 0.62–0.61 (m, 1H); 13C NMR (pyridine-d5,
150 MHz) d 109.6 (C-22), 107.1 (C-100), 100.8 (C-10), 84.4 (C-20),
81.5 (C-16), 78.7 (C-6), 78.68 (C-50), 78.64 (C-30), 78.1 (C-300), 76.3
(C-200), 71.8 (C-40), 71.5 (C-400), 68.9 (C-3), 67.8 (C-500), 67.3 (C-26),
63.4, 63.0 (C-60), 56.8, 54.6, 52.7, 43.2, 42.4, 41.2, 40.5, 38.1, 37.0,
34.7, 32.6, 32.2, 31.0, 30.3, 29.7, 29.5, 21.7, 17.7 (C-27), 17.0 (C-
19), 15.4 (C-21), 14.0 (C-18); HRMS (ESI) calcd for C38H62O13Na
[M+Na]+: 749.4083, found: 749.4077.
4.3.44. Chlorogenin 3b-O-[2-O-(b-D-galatopyranosyl)-b-D-
glucopyranoside] (60)
By the similar procedure of synthesis of 53, treatment of com-
pound 36 (52 mg, 0.03 mmol) afforded 60 (13 mg, 0.02 mmol,
49%) as a white solid: mp 250–260 °C; ½a D25
ꢁ19.6 (c 0.06, MeOH);
ꢂ
1H NMR (pyridine-d5, 600 MHz) d 5.18 (d, J = 7.8 Hz, 1H, H-100), 5.08
(d, J = 7.6 Hz, 1H, H-10), 4.61 (t, J = 8.0 Hz, 1H, H-200), 4.58–4.50 (m,
5H, H-16, H-400, H-6a0, H-600,), 4.38–4.36 (m, 1H, H-6b0), 4.30 (t,
J = 8.9 Hz, 1H, H-30), 4.23 (t, J = 8.9 Hz, 1H, H-40), 4.16–4.13 (m,
5H, H-20, H-300, H-500), 4.04–4.03 (m, 1H, H-6), 3.83–3.80 (m, 1H,
H-50), 3.59–3.56 (m, 2H, H-3, H-26a), 3.51–3.46 (m, 1H, H-26b),
2.19–2.16 (m, 1H), 2.08–2.07 (m, 3H), 1.95–1.94 (m, 1H), 1.80–
1.51 (m, 12H), 1.42–1.22 (m, 6H), 1.16 (d, J = 6.8 Hz, 3H, H-21),
1.08–1.05 (m, 1H), 0.88–0.84 (m, 1H), 0.85 (s, 3H, H-19), 0.84 (s,
3H, H-18), 0.72 (d, J = 5.3 Hz, 3H, H-27), 062–0.60 (m, 1H); 13C
NMR (pyridine-d5, 150 MHz) d 109.7 (C-22), 107.7 (C-100), 101.8
(C-10), 85.56 (C-20), 81.56 (C-16), 79.7 (C-6), 78.5 (C-50), 78.2 (C-
30), 78.0 (C-500), 75.3 (C-300), 75.0 (C-200), 71.9 (C-40), 70.5 (C-400),
69.0 (C-3), 67.3 (C-26), 63.4, 63.0 (C-60), 62.6 (C-600), 56.8, 54.5,
52.6, 50.1, 43.1, 42.4, 41.2, 40.5, 38.0, 37.1, 34.7, 32.6, 32.2, 31.0,
30.1, 29.7, 21.7, 17.8 (C-27), 17.0 (C-19), 15.5 (C-21), 14.1 (C-18);
HRMS (ESI) calcd for C39H64O14Na [M+Na]+: 779.4188, found:
779.4216.
4.3.42. Chlorogenin 3b-O-[2-O-(a-D-mannopyranosyl)-b-D-
glucopyranoside] (58)
By the similar procedure of synthesis of 53, treatment of com-
pound 34 (90 mg, 0.06 mmol) afforded 58 (40 mg, 88%) as a white
solid: mp 266 °C; ½a D25
ꢂ
ꢁ50.0 (c 0.02, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 6.18 (s, 1H, H-100), 5.17–5.15 (m, 1H, H-500), 5.04 (d, J
=7.7 Hz, 1H, H-10), 4.79–4.73 (m, 2H, H-400, H-200), 4.68–4.66 (m,
1H, H-300), 4.60–4.50 (m, 4H, H-600, H-16, H-6a0, H-6a00), 4.47 (dd,
J = 5.2, 11.3 Hz, 1H, H-6b00), 4.34 (dd, J = 5.5, 11.6 Hz, 1H, H-6b0),
4.22–4.13 (m, 3H, H-20, H-40, H-30), 3.98–3.92 (m, 1H, H-6), 3.82–
3.80 (m, 1H, H-50), 3.59–3.57 (m, 2H, H-3, H-26a), 3.51 (t,
J = 10.5 Hz, 1H, H-26b), 2.24–2.22 (m, 1H), 2.13–1.94 (m, 3H),
1.83–1.81 (m, 1H), 1.73–1.41 (m, 15H), 1.21–1.20 (m, 3H), 1.16
(d, J = 6.9 Hz, 3H, H-21), 1.09–0.88 (m, 2H), 0.85 (s, 3H, H-19),
0.76 (s, 3H, H-18), 0.71 (d, J = 5.4 Hz, 3H, H-27), 0.64–0.62 (m,
1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 102.5 (C-
100), 102.4 (C-10), 81.5 (C-16), 80.2 (C-20), 78.6 (C-50), 78.5 (C-6),
77.5 (C-30), 75.0 (C-500), 73.5 (C-300), 72.8 (C-400), 72.4 (C-40), 69.8
(C-200), 68.8 (C-3), 67.3 (C-26), 63.4, 63.6 (C-600), 63.2 (C-60), 56.8,
54.5, 52.6, 43.2, 42.4, 41.2, 40.5, 38.1, 36.9, 34.7, 32.6, 32.2, 31.0,
30.5, 29.9, 29.7, 21.7, 17.7 (C-27), 17.0 (C-19), 15.4 (C-21), 14.0
(C-18); HRMS (ESI) calcd for C39H64O14Na [M+Na]+: 779.4188,
found: 779.4182.
4.3.45. Chlorogenin 3b-O-[2-O-(b-D-lactopyranosyl)-b-D-
glucopyranoside] (61)
By the similar procedure of synthesis of 53, treatment of com-
pound 37 (73 mg, 10.05 mmol) afforded 61 (6 mg, 0.07 mmol,
42%) as a white solid: mp 281 °C; ½a D25
ꢂ
ꢁ35.9 (c 0.08, MeOH); 1H
NMR1H NMR (pyridine-d5, 600 MHz) d 6.38 (d, J = 8.1 Hz, 1H, H-
1000), 6.36 (d, J = 7.3 Hz, 1H, H-100), 5.08 (d, J = 7.5 Hz, 1H, H-10),
5.07–5.05 (m, 1H, H-500), 4.88 (s, 1H, H-2000), 4.70–4.68 (m, 1H, H-
300), 4.65 (s, 1H, H-200), 4.56–4.54 (m, 4H, H-3000, H-16, H-600), 4.53–
4.47 (m, 3H, H-6a0, H-5000, H-400), 4.38–4.36 (m, 1H, H-6b0), 4.30–
4.28 (m, 1H, H-4000), 4.26 (d, J = 7.9 Hz, 1H, H-20), 4.20–4.16 (m,
2H, H-30, H-40), 4.07–4.05 (m, 1H, H-6), 3.79–3.78 (m, 1H, H-50),
3.68–3.66 (m, 1H, H-3), 3.62–3.58 (m, 1H, H-26a), 3.51 (t,
J = 10.4 Hz, H-26b), 2.20–2.18 (m, 1H), 2.10–2.09 (m, 2H), 1.98–
1.95 (m, 1H), 1.84–1.80 (m, 1H),1.77 (d, J = 6.0 Hz, 3H, H-600),
1.76–1.52 (m, 13H), 1.66–1.62 (m, 2H), 1.45–1.20 (m, 3H), 1.15
(d, J = 6.8 Hz, 3H, H-21), 1.09 (s, 3H, H-19), 1.08–0.88 (m, 2H),
0.81 (s, 3H, H-18), 0.70 (d, J = 5.4 Hz, 3H, H-27), 0.62–0.61 (m,
1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 103.3 (C-
1000), 102.1 (C-100), 100.1 (C-10), 81.5 (C-16), 80.3 (C-400), 80.0 (C-
30), 78.6 (C-50), 77.9 (C-20), 77.7 (C-6), 74.6 (C-4000), 74.0 (C-300),
73.4 (C-200), 73.2 (C-3000), 73.0 (C-2000), 72.2 (C-40), 70.6 (C-5000), 68.9
(C-3), 67.9 (C-500), 67.3 (C-26), 63.4 (C-60), 63.0, 62.9, 56.7, 55.5,
54.5, 52.6, 43.1, 42.4, 41.2, 40.5, 38.0, 37.0, 34.7, 31.0, 30.3, 30.1,
29.7, 21.7, 19.6 (C-600), 19.0 (C-6000), 17.7 (C-27), 17.1 (C-18), 15.5
4.3.43. Chlorogenin 3b-O-[2-O-(a-D-glucopyranosyl)-b-D-
glucopyranoside] (59)
By the similar procedure of synthesis of 53, treatment of com-
pound 35 (50 mg, 0.03 mmol) afforded 59 (16 mg, 63%) as a white
solid: mp 250 °C; ½a D25
ꢂ
ꢁ62.5 (c 0.08, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.30 (d, J = 7.7 Hz, 1H, H-100), 5.07 (d, J = 7.7 Hz, 1H, H-
10), 4.66–4.63 (m, 2H, H-16, H-6), 4.58–4.54 (bt, J = 12.0 Hz, 1H, H-
3), 4.52 (dd, J = 2.4, 12.0 Hz, 1H, H-6a0), 4.43 (dd, J = 12.0, 5.1 Hz,
1H, H-6b0), 4.39–4.36 (m, 2H, H-40, H-400), 4.33 (t, J = 9.2 Hz, 1H,

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
133
(C-21), 14.2 (C-19); HRMS (ESI) calcd for C45H74O17Na [M+Na]+:
909.4818, found: 909.4884.
4.3.49. Chlorogenin 3b-O-[4-O-(b-
glucopyranoside] (64)
L-arabinopyranosyl)-b-D-
By the similar procedure of synthesis of 53, treatment of com-
pound 40 (115 mg, 0.08 mmol) afforded 64 (25 mg, 43%) as a white
4.3.46. Chlorogenin 3b-O-[2-O-(a-L-rhamnopyranosyl)-b-D-
glucopyranoside] (62)
solid: mp 275–285 °C; ½a D25
ꢂ
ꢁ29.8 (c 0.09, MeOH); 1H NMR (pyri-
By the similar procedure of synthesis of 53, treatment of com-
pound 38 (90 mg, 0.07 mmol) afforded 62 (34 mg, 0.05 mmol,
dine-d5, 600 MHz) d
5.07 (d, J = 7.6 Hz, 1H, H-100), 5.02 (d,
J = 7.7 Hz, 1H, H-10), 4.55 (m, 3H, H-6a0, H-16, H-200), 4.47 (d,
J = 11.5 Hz, 1H, H-6b0), 4.38 (t, J = 9.3 Hz, 1H, H-40), 4.27 (m, 3H,
H-5a00, H-30, H-400), 4.13 (dd, J = 2.4, 8.8 Hz, 1H, H-300), 4.08 (t,
J = 8.3 Hz, 1H, H-20), 4.02 (m, 1H, H-6), 3.77 (m, 2H, H-50, H-5b00),
3.60 (m, 2H, H-3, H-26a), 3.51 (t, J = 10.6 Hz, 1H, H-26b), 2.21–
2.19 (m, 1H), 2.06–2.04 (m, 2H), 1.96–1.94 (m, 1H), 1.80–1.78
(m, 1H), 1.72–1.39 (m, 16H), 1.20–1.16 (m, 2H), 1.16 (d,
J = 6.9 Hz, 3H, H-21), 1.06–1.04 (m, 1H), 0.89–0.88 (m, 1H), 0.86
(s, 3H, H-19), 0.77 (s, 3H, H-18), 0.71 (d, J = 5.2 Hz, 3H, H-27),
0.63–0.61 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.67 (C-
22), 106.1 (C-100), 102.4 (C-10), 81.5 (C-16), 81.2 (C-40), 78.2 (C-6),
76.9 (C-30), 76.9 (C-50), 75.5 (C-20), 75.0 (C-300), 72.9 (C-200), 70.0
(C-400), 68.8 (C-3), 68.2 (C-500), 67.3 (C-26), 63.4, 62.2 (C-60), 56.8,
54.6, 52.6, 50.1, 43.1, 42.4, 41.2, 40.5, 38.1, 37.0, 34.7, 32.6, 32.2,
31.0, 30.3, 29.9, 21.7, 17.7 (C-27), 17.0 (C-19), 15.4 (C-21), 14.0
(C-18); HRMS (ESI) calcd for C38H62O13Na [M+Na]+: 749.4083,
found: 749.4076.
70.0%) as a white solid: mp 219 °C; ½a D25
ꢁ39.9 (c 0.05, MeOH);
ꢂ
1H NMR (pyridine-d5, 600 MHz) d 6.35–6.33 (m, 1H, H-100), 5.10
(d, J = 7.7 Hz, 1H, H-10), 5.04 (m, 1H, H-500), 4.76 (m, 1H, H-200),
4.61 (dd, J = 3.4, 9.3 Hz, 1H, H-300), 4.56 (dd, J = 7.3, 14.9 Hz, 1H,
H-16), 4.50 (dd, J = 2.0, 11.8 Hz, 1H, H-6a0), 4.35 (m, 2H, H-6b0,
H-400), 4.27 (t, J = 8.2 Hz, 1H, H-20), 4.21 (t, J = 9.0 Hz, 1H, H-30),
4.16 (t, J = 9.0 Hz, 1H, H-40), 4.11 (m, 1H, H-6), 3.79 (m, 1H, H-
50), 3.60 (m, 2H, H-3, H-26a), 3.51 (t, J = 10.7 Hz, 1H, H-26b),
2.23–1.79 (m, 8H), 1.69–1.38 (m, 13H), 1.80 (d, J = 6.2 Hz, 3H,
H-600), 1.25–1.22 (m, 2H), 1.16 (d, J = 6.9 Hz, 3H, H-21), 1.08–
1.06 (m, 1H), 0.97 (s, 3H, H-19), 0.88–0.86 (m, 1H), 0.85 (s, 3H,
H-18), 0.71 (d, J = 5.4 Hz, 3H, H-27), 0.64–0.62 (m, 1H); 13C
NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 102.6 (C-100), 100.0
(C-10), 81.5 (C-16), 80.0 (C-30), 78.6 (C-50), 78.5 (C-20), 77.4 (C-6),
74.6 (C-400), 73.2 (C-300), 72.9 (C-200), 72.2 (C-40), 69.8 (C-500), 68.9
(C-3), 67.3 (C-26), 63.5, 63.1 (C-60), 56.8, 54.5, 52.6, 43.1, 42.4,
41.2, 40.5, 38.2, 37.1, 34.7, 32.6, 32.3, 31.0, 30.3, 29.7, 29.4,
21.7, 19.1 (C-600), 17.8 (C-27), 17.0 (C-18), 15.5 (C-21), 14.1 (C-
19); HRMS (ESI) calcd for C39H64O13Na [M+Na]+: 763.4239, found:
763.4254.
4.3.50. Chlorogenin 3b-O-[4-O-(b-L-fucopyranosyl)-b-D-
glucopyranoside] (65)
By the similar procedure of synthesis of 53, treatment of com-
pound 41 (60 mg, 0.04 mmol) afforded 65 (20 mg, 65%) as a white
solid: mp 268 °C; ½a D25
ꢂ
ꢁ16.9 (c 0.08, MeOH); 1H NMR (pyridine-d5,
4.3.47. Chlorogenin 3b-O-{2-O-[4-O-(a-L-rhamnopyranosyl)-a-L-
600 MHz) d 5.26 (d, J = 7.8 Hz, 1H, H-100), 5.00 (d, J = 7.2 Hz, 1H, H-
10), 4.58–4.56 (m, 2H, H-16, H-6a0), 4.48 (t, J = 9.6 Hz, 1H, H-200),
4.44 (dd, J = 12.0, 4.8 Hz, 1H, H-6b0), 4.32–4.29 (m, 2H, H-40, H-
400) 4.11 (dd, J = 9.6, 3.6 Hz, 1H, H-300), 4.09–4.02 (m, 3H, H-20, H-
30, H-6), 3.86–3.83 (m, 2H, H-500, H-50), 3.64–3.62 (m, 1H, H-3),
3.60–3.58 (m, 1H, H-26a), 3.52 (t, J = 10.8 Hz, 1H, H-26b), 3.12 (d,
J = 12.8 Hz, 1H, OH), 2.10–2.06 (m, 1H), 1.98–1.85 (m, 3H), 1.76–
1.56 (m, 15H), 1.54 (d, J = 6.6 Hz, 3H, H-600), 1.48–1.45 (m, 2H),
1.23–1.21 (m, 2H), 1.10–1.08 (m, 1H), 1.16 (d, J = 6.6 Hz, 3H, H-
21), 0.91–0.89 (m, 1H), 0.86 (s, 3H, H-19), 0.76 (s, 3H, H-18), 0.71
(d, J = 6.0 Hz, 3H, H-27), 0.66–0.65 (m, 1H); 13C NMR (pyridine-
d5, 150 MHz) d 109.7 (C-22), 107.4 (C-100), 102.5 (C-10), 81.7 (C-
400), 81.5 (C-16), 78.3 (C-30), 78.3 (C-40), 77.1 (C-50), 75.8 (C-300),
75.4 (C-20), 73.9 (C-200), 73.0 (C-6), 72.4 (C-500), 68.9 (C-3), 67.3
(C-26), 63.4, 63.1 (C-60), 56.8, 54.6, 52.6, 43.1, 42.5, 41.2, 40.5,
38.1, 37.0, 34.7, 32.6, 31.0, 31.0, 30.4, 29.9, 29.7, 21.7, 18.5 (C-600),
18.4 (C-27), 17.8 (C-19), 16.2 (C-21), 14.8 (C-18); HRMS (ESI) calcd
for C39H64O13Na [M+Na]+: 763.4239, found: 763.4251.
rhamnopyranosyl]-b- -glucopyranoside} (63)
D
To a solution of 39 (73 mg, 10.05 mmol) in acetic acid (80%,
4 mL) was stirred at 60 °C for 24 h. The mixture was concentrated
under vacuum and purified by column chromatography on silica
gel (EtOAc/hexane, 2:1), and the crude was then followed the
similar method for the preparation of 53. 63 (6 mg, 0.07 mmol,
41%) was obtained as a white solid: mp 250 °C; ½a D25
ꢁ33.7 (c
ꢂ
0.02, MeOH); 1H NMR (pyridine-d5, 600 MHz) d 6.38 (s, 1H, H-
1000), 6.36 (s, 1H, H-100), 5.08 (d, J = 7.5 Hz, 1H, H-10), 5.06–4.95
(m, 1H, H-500), 4.88 (s, 1H, H-2000), 4.71–4.68 (m, 1H, H-300), 4.65
(s, 1H, H-200), 4.56–4.55 (m, 2H, H-3000, H-16), 4.50–4.38 (m, 3H,
H-6a0, H-5000, H-400), 4.36–4.32 (m, 1H, H-6b0), 4.30–4.28 (m, 1H,
H-4000), 4.26 (d, J = 7.9 Hz, 1H, H-20), 4.18–4.12 (m, 2H, H-30, H-
40), 4.06–4.02 (m, 1H, H-6), 3.78–3.77 (m, 1H, H-50), 3.68–3.66
(m, 1H, H-3), 3.60–3.58 (m, 1H, H-26a), 3.51 (t, J = 10.4 Hz, H-
26b), 2.20–1.80 (m, 6H), 1.74–1.57 (m, 6H), 1.48–1.18 (m, 12H),
1.66 (d, J = 6.3 Hz, 3H, H-6000), 1.15 (d, J = 6.8 Hz, 3H, H-21), 1.09
(s, 3H, H-19), 0.89–0.85 (m, 1H), 0.81 (s, 3H, H-18), 0.70 (d,
J = 5.4 Hz, 3H, H-27), 0.65–0.55 (m, 1H); 13C NMR (pyridine-d5,
150 MHz) d 109.6 (C-22), 103.3 (C-1000), 102.1 (C-100), 100.1 (C-
10), 80.3 (C-16), 80.0 (C-400), 78.6 (C-30), 77.9 (C-50), 77.7 (C-20),
74.6 (C-6), 74.0 (C-4000), 73.4 (C-300), 73.2 (C-200), 73.0 (C-3000),
72.2 (C-2000), 70.6 (C-40), 68.9 (C-5000), 67.9 (C-3), 67.3 (C-500), 64.9
(C-26), 63.4 (C-60), 63.1, 56.8, 54.7, 52.6, 43.3, 42.4, 41.2, 38.2,
37.1, 34.7, 32.6, 32.3, 34.7, 32.6, 31.0, 30.4, 29.7, 21.7, 19.3 (C-
600), 19.1 (C-6000), 17.7 (C-27), 17.0 (C-18), 15.4 (C-21), 14.0 (C-
19); HRMS (ESI) calcd for C45H74O17Na [M+Na]+: 909.4818, found:
909.4884.
4.3.51. Chlorogenin 3b-O-[4-O-(b-L-xylopyranosyl)-b-D-
glucopyranoside] (66)
By the similar procedure of synthesis of 53, treatment of com-
pound 42 (72 mg, 0.05 mmol) afforded 66 (22 mg, 60%) as white
solids: mp 310 °C; ½a D25
ꢂ
ꢁ13.5 (c 0.05, MeOH); 1H NMR (pyridine-
d5, 600 MHz) d 5.38 (d, J = 7.6 Hz, 1H, H-100), 5.02 (d, J = 7.7 Hz,
1H, H-10), 4.58–4.56 (m, 2H, H-16, H-6a0), 4.44 (m, 1H, H-6b0),
4.36–4.31 (m, 3H, H-30, H-40, H-5a00), 4.21 (m, 1H, H-400), 4.17 (t,
J = 8.8 Hz, 1H, H-300), 4.11–4.05 (m, 3H, H-200, H-6, H-20), 3.87 (m,
1H, H-50), 3.71 (t, J = 10.7 Hz, 1H, H-5b00), 3.61 (m, 1H, H-3), 3.59
(m, 1H, H-26a), 3.51 (t, J = 10.7 Hz, 1H, H-26b), 3.13 (d,
J = 12.6 Hz, 1H, OH), 2.23 (m, 1H), 2.09–2.07 (m, 3H), 1.98–1.97
(m, 1H), 1.84–1.80 (m, 1H), 1.74–1.44 9 (m, 15H), 1.20–1.19 (m,
2H), 1.16 (d, J = 7.0 Hz, 3H, H-21), 1.11–1.08 (m, 1H), 0.90–0.87
(m, 1H), 0.86 (s, 3H, H-19), 0.75 (s, 3H, H-18), 0.71 (d, J = 5.8 Hz,
3H, H-27), 0.66–0.65 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d
109.7 (C-22). 107.5 (C-100), 102.4 (C-10), 81.5 (C-16), 81.5 (C-40),
78.9 (C-300), 78.39 (C-30), 78.31 (C-20), 77.2 (C-50), 76.6 (C-200), 75.4
4.3.48. Chlorogenin 3b-O-[2,4-di-O-(a-L-rhamnopyranosyl)-b-D-
glucopyranoside] (2)22
By the similar procedure of synthesis of 53, treatment of 51
(102 mg, 0.06 mmol) afforded 2 (38 mg, 73%) as a white solid:
mp 247 °C; ½a 2D5
ꢂ
ꢁ72.5 (c 0.06, MeOH); The NMR data are similar
to the Ref.22
.
HRMS (ESI) calcd for C45H74O17Na [M+Na]+:
909.4818, found: 909.4884.

134
Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
(C-6), 71.4 (C-400), 68.9 (C-3), 68.1 (C-500), 67.3 (C-26), 63.4, 62.9 (C-
60), 56.8, 54.6, 52.6, 43.1, 42.5, 41.2, 40.5, 38.1, 37.0, 34.7, 32.6,
32.3, 31.0, 30.3, 29.9, 29.7, 21.7, 17.8 (C-27), 17.0 (C-19), 15.5 (C-
21), 14.0 (C-18); HRMS (ESI) calcd for C38H62O13Na [M+Na]+:
749.4083, found: 749.4055.
1H), 3.59 (dd, 1H, J = 12, 4.8 Hz, H-26a), 3.50 (t, J = 12 Hz, 1H, H-
26b), 2.14–2.11 (m, 2H), 2.05–1.81 (m, 5H), 1.72–1.45 (m, 16H),
1.16 (d, J = 6.7 Hz, 3H, H-21), 1.10–1.06 (m, 2H), 0.86 (s, 3H, H-
19), 0.77 (s, 3H, H-18), 0.71 (d, J = 5.3 Hz, 3H, H-27), 0.67–0.64
(m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 105.3
(C-100), 102.3 (C-10), 81.6, 81.5, 78.8, 78.6, 78.2, 77.2, 76.7, 75.9,
75.3, 75.2, 75.0, 73.6, 71.9, 71.5, 68.8, 67.2, 65.7, 64.8, 63.4, 62.9,
62.5, 56.7, 54.5, 52.6, 43.1, 42.4, 41.2, 40.4, 38.1, 37.0, 34.6, 32.5,
32.2, 31.0, 29.9, 29.6, 21.7, 17.7, 17.0, 15.4, 14.0; HRMS (ESI) calcd
for C39H64O14Na [M+Na]+: 779.4188, found: 779.4201.
4.3.52. Chlorogenin 3b-O-[4-O-(b-D-xylopyranosyl)-b-D-
glucopyranoside] (67)
By the similar procedure of synthesis of 53, treatment of com-
pound 43 (74 mg, 0.05 mmol) afforded 67 (15 mg, 40%) as a white
solid: mp 229 °C; ½a D25
ꢂ
ꢁ27.5 (c 0.04, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.16 (d, J = 7.8 Hz, 1H, H-100), 5.04 (d, J = 7.8 Hz, 1H, H-
10), 4.58 (m, 2H, H-6a0, H-16), 4.50 (d, J = 11.5 Hz, 1H, H-6b0), 4.37
(t, J = 9.2 Hz, 1H, H-40), 4.27 (m, 2H, H-30, H-5a00), 4.18 (m, 1H, H-
400), 4.14 (t, J = 8.8 Hz, 1H, H-300), 4.10 (t, J = 8.2 Hz, 1H, H-20), 4.04
(m, 2H, H-200, H-6), 3.83 (m, 1H, H-50), 3.69 (t, J = 10.6 Hz, 1H, H-
5b00), 3.61 (m, 2H, H-3, H-26a), 3.51 (t, J = 10.5 Hz, 1H, H-26b),
2.21–2.18 (m, 1H), 2.06–2.05 (m, 2H), 1.95–1.94(m, 1H), 1.82–
1.80 (m, 1H), 1.73–1.39 (m, 14H), 1.19–1.18 (m,3H), 1.16 (d,
J = 6.9 Hz, 3H, H-21), 1.06–0.89 (m, 2H), 0.86 (s, 3H, H-19), 0.77
(s, 3H, H-18), 0.71 (d, J = 5.3 Hz, 3H, H-27), 0.64–0.62 (m, 1H);
13C NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 106.0 (C-100),
102.4 (C-10), 81.5 (C-16), 81.4 (C-40), 78.8 (C-300), 78.3 (C-6), 76.9
(C-30), 76.9 (C-50), 75.5 (C-20), 75.4 (C-200), 71.3 (C-400), 68.8 (C-3),
67.8 (C-500), 67.3 (C-26), 63.4, 62.2 (C-60), 56.8, 54.6, 52.2, 43.1,
42.4, 41.2, 40.5, 38.1, 37.0, 34.7, 32.6, 32.2, 31.0, 30.4, 29.9, 29.7,
21.7, 17.7 (C-27), 17.0 (C-19), 15.4 (C-21), 14.0 (C-18); HRMS
(ESI) calcd for C38H62O13Na [M+Na]+: 749.4083, found: 749.4082.
4.3.55. Chlorogenin 3b-O-[4-O-(b-D-galatopyranosyl)-b-D-
glucopyranoside] (70)
By the similar procedure of synthesis of 53, treatment of com-
pound 46 (49 mg, 0.03 mmol) afforded 70 (10 mg, 42%) as a white
solid: mp 285 °C; ½a D25
ꢂ
ꢁ17.5 (c 0.04, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.13 (d, J = 7.6 Hz, 1H, H-100), 5.02 (d, J = 7.8 Hz, 1H, H-
10), 4.57–4.53 (m, 3H, H-16, H-200, H-6a0), 4.50–4.46 (m, 3H, H-6b0,
H-400, H-6a00), 4.42–4.39 (m, 1H, H-6b00), 4.35 (t, J = 8.9 Hz, 1H, H-40),
4.26 (t, J = 8.8 Hz, 1H, H-30), 4.17–4.12 (m, 2H, H-300, H-500), 4.07 (d,
J = 8.2 Hz, 1H, H-20), 4.01–3.98 (m, 1H, H-6), 3.85–3.82 (m, 1H, H-
50), 3.60–3.55 (m, 2H, H-3, H-26a), 3.51 (t, J =10.5 Hz, 1H, H-26b),
2.25–2.07 (m, 3H), 1.98–1.83 (m, 2H), 1.72–1.45 (m, 15H), 1.34–
1.20 (m, 3H), 1.16 (d, J = 6.7 Hz, 3H, H-21), 1.09–0.92 (m, 2H),
0.86 (s, 3H, H-19), 0.76 (s, 3H, H-18), 0.71 (d, J = 5.0 Hz, 3H, H-
27), 0.66–0.65 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6
(C-22), 106.3 (C-100), 102.4 (C-10), 82.6 (C-40), 81.5 (C-16), 78.2 (C-
6), 77.7 (C-500), 77.1 (C-30), 76.7 (C-50), 75.6 (C-300), 75.4 (C-20),
72.9 (C-200), 70.5 (C-400), 68.8 (C-3), 67.3 (C-26), 63.4, 62.7 (C-60),
62.5 (C-600), 56.8, 54.6, 52.6, 43.1, 42.4, 41.2, 40.5, 38.1, 37.0, 34.7,
32.6, 32.2, 31.0, 30.3, 29.9, 29.7, 21.7, 17.7 (C-27), 17.0 (C-19),
4.3.53. Chlorogenin 3b-O-[4-O-(a-D-mannopyranosyl)-b-D-
glucopyranoside] (68)
By the similar procedure of synthesis of 53, treatment of com-
pound 44 (100 mg, 0.06 mmol) afforded 68 (22 mg, 45%) as white
15.4 (C-21), 14.0 (C-18); HRMS (ESI) calcd for
C39H64O14Na
[M+Na]+: 779.4188, found: 779.4187.
solids: mp 290 °C; ½a D25
ꢂ
+2.5 (c 0.04, MeOH); 1H NMR (pyridine-
d5, 600 MHz) d 6.54 (d, J = 3.3 Hz, 1H, H-100), 4.97 (d, J = 7.8 Hz,
1H, H-10), 4.91–4.90 (m, 1H, H-200), 4.71 (d, J = 11.2 Hz, 1H, H-
6a00), 4.68–4.63 (m, 3H, H-300, H-400, H-500), 4.60 (t, J = 9.4 Hz, 1H,
H-40), 4.56 (q, J = 7.5 Hz, 1H, H-16), 4.42–4.38 (m, 3H, H-6a0, H-
6b0, H-6b00), 4.29 (t, J = 9.4 Hz, 1H, H-30), 4.01–3.99 (m, 1H, H-6),
3.96 (dd, J = 9.4, 8.1 Hz, 1H, H-20), 3.71–3.69 (m, 1H, H-50), 3.61–
3.57 (m, 2H, H-3, H-26a), 3.51 (t, J = 10.6 Hz, 1H, H-26b), 3.11 (d,
J = 12.5 Hz, 1H, OH), 2.23–2.21 (m, 1H), 2.12–1.96 (m, 3H), 1.83–
1.80 (m, 1H), 1.74–1.43 (m, 15H), 1.34–1.18 (m, 3H), 1.16 (d,
J = 6.9 Hz, 3H, H-21), 1.09–1.08 (m, 1H), 0.88–0.87 (m, 1H), 0.86
(s, 3H, H-19), 0.75 (s, 3H, H-18), 0.71 (d, J = 6.9 Hz, 3H, H-27),
0.65–0.64 (m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.7 (C-
22), 103.3 (C-100), 102.3 (C-10), 81.5 (C-16), 79.2 (C-30), 78.1 (C-6),
77.0 (C-50), 76.8 (C-500), 76.4 (C-40), 75.9 (C-20), 73.7 (C-400), 73.0
(C-200), 69.8 (C-300), 68.9 (C-3), 67.3 (C-26), 63.7 (C-600), 63.4, 62.4
(C-60), 56.8, 54.6, 52.6, 50.1, 43.1, 42.4, 41.2, 40.5, 38.1, 37.0,
34.7, 32.6, 32.2, 31.0, 30.3, 29.7, 21.7, 17.8 (C-27), 17.0 (C-19),
4.3.56. Chlorogenin 3b-O-[4-O-(b-D-lactopyranosyl)-b-D-
glucopyranoside] (71)
By the similar procedure of synthesis of 53, treatment of com-
pound 47 (98 mg, 0.05 mmol) afforded 71 (14 mg, 32%) as white
solids: mp 307–315 °C; ½a D25
ꢂ
ꢁ31.0 (c 0.06, MeOH); 1H NMR (pyri-
dine-d5, 600 MHz) d 5.19 (d, J = 8.1 Hz, 1H, H-100), 5.07 (d, J = 7.7 Hz,
1H, H-1000), 5.01 (d, J = 7.7 Hz, 1H, H-10), 4.46–4.59 (m, 8H, H-16, H-
6a0, H-6b0, H-6a00, H-6b00, H-2000, H-4000, H-6a000), 4.41–4.39 (m, 1H, H-
6b000), 4.34 (t, J = 9.0 Hz, 1H, H-40), 4.28–4.25 (m, 3H, H-400, H-300, H-
30), 4.15–4.09 (m, 3H, H-3000, H-5000, H-200), 4.05–4.01 (m, 3H, H-6, H-
20, H-500), 3.85–3.79 (m, 1H, H-50), 3.59–3.58 (m, 2H, H-3, H-26a),
3.51–3.48 (m, 1H, H-26b), 2.24–2.23 (m, 1H), 2.13–1.95 (m, 3H),
1.84–1.80 (m, 1H), 1.73–1.44 (m, 15H), 1.32–1.18 (m, 3H), 1.16
(d, J = 6.9 Hz, 3H, H-21), 1.08–0.92 (m, 2H), 0.86 (s, 3H, H-19),
0.76 (s, 3H, H-18), 0.71 (d, J = 5.5 Hz, 3H, H-27), 0.67–0.65 (m,
1H); 13C NMR (pyridine-d5, 150 MHz) d 109.6 (C-22), 106.2 (C-
1000), 104.9 (C-100), 102.4 (C-10), 82.0 (C-400), 81.56 (C-40), 81.53 (C-
16), 78.2 (C-6), 77.7 (C-5000), 77.1 (C-500), 76.9 (C-30), 76.8 (C-300),
76.7 (C-50), 75.6 (C-3000), 75.3 (C-20), 74.7 (C-200), 72.8 (C-2000), 70.5
(C-4000), 68.8 (C-3), 67.3 (C-26), 63.4, 62.5 (C-60), 62.4 (C-600), 62.2
(C-6000), 56.8, 54.5, 52.6, 43.1, 42.4, 41.2, 40.5, 38.1, 37.0, 34.7,
32.6, 32.2, 30.9, 30.3, 29.9, 29.7, 21.7, 17.7 (C-27), 17.0 (C-19),
15.5 (C-21), 14.0 (C-18); HRMS (ESI) calcd for
C39H64O14Na
[M+Na]+: 779.4188, found: 779.4186.
4.3.54. Chlorogenin 3b-O-[4-O-(b-D-glucopyranosyl)-b-D-
glucopyranoside] (69)
By the similar procedure of synthesis of 53, treatment of com-
pound 45 (92 mg, 0.06 mmol) afforded 69 (20 mg, 45%) as a white
15.4 (C-21), 14.0 (C-18); HRMS (ESI) calcd for
C45H74O19Na
[M+Na]+: 941.4717, found: 941.4797.
solid: mp 278 °C; ½a D25
ꢂ
ꢁ32.7 (c 0.02, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.22 (d, J = 7.9 Hz, 1H, H-100), 5.02 (d, J = 7.7 Hz, 1H, H-
10), 4.90 (dd, J = 4.2, 1.8 Hz, 1H, H-400), 4.64–4.58 (m, 2H, H-500, H-
6a00), 4.57–4.52 (m, 2H, H-6, H-400), 4.48 (dd, J = 2.4, 12 Hz, 1H, H-
6b00), 4.40–4.36 (m, 3H, H-40, H-6b00, H-16), 4.37–4.35 (m, 1H, H-
50), 4.34 (t, J = 11.0 Hz, 1H, H-6b0), 4.34–4.31 (m, 1H, H-50), 4.28
(t, J = 12 Hz, 1H, H-6a0), 4.24–4.22 (m, 2H, H-30, H-300), 4.13 (dd,
J = 7.9, 9.0 Hz, H-20), 4.08–3.98 (m, 3H, H-200, H-3), 3.85–3.83 (m,
4.3.57. Chlorogenin 3b-O-[4-O-(a-L-rhamnopyranosyl)-b-D-
glucopyranoside] (72)
By the similar procedure of synthesis of 53, treatment of com-
pound 48 (125 mg, 0.09 mmol) afforded 72 (40 mg, 62%) as a white
solid: mp 229 °C; ½a D25
ꢂ
ꢁ66.1 (c 0.06, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 5.88 (s, 1H, H-100), 5.00 (d, J = 7.8 Hz, 1H, H-10), 4.98 (m,
1H, H-500), 4.70 (d, J =1.3 Hz, 1H, H-200), 4.57–4.50 (m, 2H, H-300,

Y.-H. Wang et al. / Carbohydrate Research 375 (2013) 118–135
135
H-16), 4.45–4.39 (m, 1H, H-40), 4.35 (t, J = 9.4 Hz, 1H, H-400), 4.26 (d,
J = 11.3 Hz, 1H, H-6a0), 4.15–4.05 (m, 2H, H-30, H-6b0), 4.00–3.87
150 MHz) d 109.6 (C-22), 103.7 (C-10000), 102.7 (C-1000), 102.6 (C-
100), 99.9 (C-10), 81.5 (C-16), 80.8 (C-400), 78.6 (C-20), 78.2 (C-30),
78.1 (C-40), 77.5 (C-6), 77.3 (C-50), 74.6 (C-4000), 74.5 (C-40000), 73.7
(C-300), 73.4 (C-200), 73.3 (C-30000), 73.2 (C-3000), 73.1 (C-20000), 72.9 (C-
2000), 70.8 (C-50000), 69.9 (C-5000), 68.9 (C-3), 68.7 (C-500), 67.3 (C-26),
63.4, 61.7 (C-60), 56.8, 54.5, 52.6, 43.1, 42.4, 41.2, 40.5, 38.1, 37.1,
34.7, 32.6, 32.2, 31.0, 30.2, 29.7, 29.3, 21.7, 19.3 (C-600), 19.1 (C-
6000), 18.9 (C-60000), 17.7 (C-27), 17.0 (C-18), 15.4 (C-21), 14.0 (C-
19); HRMS (ESI) calcd for C51H84O21Na [M+Na]+: 1055.5397, found:
1055.5359.
(m, 2H, H-6, H-20), 3.69–3.50 (m, 3H, H-3, H-50, H-26
a), 3.51–
3.48 (m, 1H, H-26b), 2.24–2.19 (m, 2H), 2.11–1.83 (m, 5H), 1.73
(d, J = 6.2 Hz, 3H, H-600), 1.73–1.44 (m, 15H), 1.21–1.08 (m, 2H),
1.16 (d, J = 6.9 Hz, 3H, H-21), 0.90–0.87 (m, 1H), 0.86 (s, 3H, H-
19), 0.77 (s, 3H, H-18), 0.71 (d, J = 4.9 Hz, 3H, H-27), 0.67–0.61
(m, 1H); 13C NMR (pyridine-d5, 150 MHz) d 109.7 (C-22), 103.1
(C-100), 102.4 (C-10), 81.5 (C-16), 78.9 (C-40), 78.2 (C-6), 77.5 (C-
50), 77.2 (C-30), 75.9 (C-20), 74.4 (C-400), 73.2 (C-300), 73.1 (C-200),
70.8 (C-500), 68.9 (C-3), 67.3 (C-26), 63.5, 62.0 (C-60), 56.8, 54.6,
52.6, 43.1, 42.5, 41.3, 40.5, 38.1, 37.0, 34.7, 32.6, 32.3, 31.1, 30.4,
29.9, 29.7, 21.8, 19.0 (C-600), 17.8 (C-27), 17.1 (C-19), 15.5 (C-21),
14.0 (C-18); HRMS (ESI) calcd for C39H64O13Na [M+Na]+:
763.4239, found: 763.4281.
Acknowledgements
We gratefully acknowledge the National Science Council of Tai-
wan ROC (NSC 98–2320-B-002-017-MY3) and Academia Sinica for
financial support. We thank Professor Y. S. Edmond Cheng at the
Genomics Research Center of Academia Sinica for the influenza
virus assay.
4.3.58. Chlorogenin 3b-O-{4-O-[4-O-(a-L-rhamnopyranosyl)-a-L-
rhamnopyranosyl]-b- -glucopyranoside} (73)
D
By the similar procedure for the synthesis of 63, treatment of
compound 49 (88 mg, 0.054 mmol) afforded 73 (19.5 mg,
Supplementary data
0.022 mmol, 41%) as a white solid: mp 238 °C; ½a D25
ꢁ41.7 (c
ꢂ
0.05, MeOH); 1H NMR (pyridine-d5, 600 MHz) d 6.38 (s, 1H, H-
1000), 6.38 (s, 1H, H-100), 4.99 (d, J = 7.5 Hz, 1H, H-10), 4.95–4.88 (m,
1H, H-500), 4.88 (s, 1H, H-2000), 4.73–4.68 (m, 1H, H-300), 4.62 (s,
1H, H-200), 4.58–4.54 (m, 2H, H-3000, H-16), 4.52–4.48 (m, 3H, H-
6a0, H-5000, H-400), 4.45–4.41 (m, 1H, H-40), 4.36–4.32 (m, 1H, H-
6b0), 4.30–4.28 (m, 1H, H-4000), 4.26 (d, J = 7.9 Hz, 1H, H-20), 4.22–
4.12 (m, 2H, H-30), 4.06–4.02 (m, 1H, H-6), 3.78–3.76 (m, 1H, H-
Supplementary data (1D and 2D NMR spectra for compounds)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.carres.2013.04.022.
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4.3.59. Chlorogenin 3b-O-{2-O-(
O-( -rhamnopyranosyl)- -rhamnopyranosyl]-b-
glucopyranoside} (74)
By the similar procedure of synthesis of 63, treatment of 52
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and hydrogenation afforded 74 (14 mg, 31%) as a white solid: mp
a-L-rhamnopyranosyl)-4-O-[4-
a-L
a-
L
D-
220 °C;
½
a 2D5
ꢂ
ꢁ89.9 (c 0.05, MeOH); 1H NMR (pyridine-d5,
600 MHz) d 6.38 (s, 1H, H-1000), 6.30 (s, 1H, H-10000), 5.84 (s, 1H, H-
100), 5.06–5.01 (m, 1H, H-5000), 5.00 (d, J = 7.8 Hz, 1H, H-10), 4.95–
4.91 (m, 1H, H-500), 4.91 (d, J = 0.7 Hz, 1H, H-20000), 4.81 (d,
J = 1.6 Hz, 1H, H-2000), 4.62 (dd, J = 3.1, 9.2 Hz, 1H, H-3000), 4.57–
4.52 (m, 3H, H-300, H-16, H-200), 4.52 (dd, J = 3.2, 9.2 Hz, 1H, H-
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a
3.50–3.45 (m, 2H, H-50, H-26b), 2.22–1.81 (m, 5H), 1.79 (d,
J = 6.1 Hz, 3H, H-6000), 1.77–1.64 (m, 8H), 1.63 (d, J = 6.5 Hz, 3H, H-
60000), 1.60 (d, J = 6.3 Hz, 3H, H-600), 1.48–1.42 (m, 2H), 1.34–1.17
(m, 4H), 1.16 (d, J = 6.9 Hz, 3H, H-21), 1.1–0.95 (m, 1H), 0.96 (s,
3H, H-19), 0.91–0.89 (m, 1H), 0.85 (s, 3H, H-18), 0.71 (d,
J = 5.4 Hz, 3H, H-27), 0.67–0.65 (m, 1H); 13C NMR (pyridine-d5,