Selective formation of glycosidic linkages of N-unsubstituted 4-hydroxyquinolin-2-(1H)-ones

Article abstract of DOI:10.1016/j.carres.2010.01.023

A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1H)-ones into 4-(tetra-O-acetyl-β-d-glucopyranosyloxy)quinolin-2(1H)-ones is reported. Four glycosyl donors including tetra-O-acetyl-α-d-glucopyranosyl bromide, β-d-glu

Full text of DOI:10.1016/j.carres.2010.01.023

Carbohydrate Research 345 (2010) 768–779
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Selective formation of glycosidic linkages of N-unsubstituted
4-hydroxyquinolin-2-(1H)-ones
b,
Roman Kimmel a, Stanislav Kafka a, , Janez Košmrlj
*
*
a Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlin, 762 72 Zlin, Czech Republic
b Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia
a r t i c l e i n f o
a b s t r a c t
Article history:
A comparative study for selective glucosylation of N-unsubstituted 4-hydroxyquinolin-2(1H)-ones into
Received 4 November 2009
Received in revised form 25 January 2010
Accepted 29 January 2010
Available online 4 February 2010
4-(tetra-O-acetyl-b-
ing tetra-O-acetyl-
tetra-O-acetyl- -glucopyranosyl trichloroacetimidate were tested, along with different promoters
and reaction conditions. The best results were obtained with tetra-O-acetyl- -glucopyranosyl bromide
with Cs2CO3 in CH3CN. In some cases the 4-O-glucosylation of the quinolinone ring was accompanied by
2-O-glucosylation yielding the corresponding 2,4-bis(tetra-O-acetyl-b- -glucopyranosyloxy)quinoline.
Next, 4-(tetra-O-acetyl-b- -glucopyranosyloxy)quinolin-2(1H)-ones were deacetylated into 4-(b-
D
-glucopyranosyloxy)quinolin-2(1H)-ones is reported. Four glycosyl donors includ-
a
-
D
-glucopyranosyl bromide, b- -glucose pentaacetate, glucose tetraacetate and
D
a
-D
a
-D
ˇ
Dedicated to Professor Marijan Kocevar on
D
the occasion of his 60th birthday.
D
D-
glucopyranosyloxy)quinolin-2(1H)-ones with Et3N in MeOH. In some instances the deacetylation was
accompanied by the sugar–aglycone bond cleavage. Structure elucidation, complete assignment of proton
and carbon resonances as well as assignment of anomeric configuration for all the products under inves-
tigation were performed by 1D and 2D NMR spectroscopy.
Keywords:
4-Hydroxyquinolin-2(1H)-ones
Glycosylation
Koenigs–Knorr method
Deacetylation
NMR structure elucidation
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
uretic kidney hormone that also could influence sodium
transport in nonkidney tissues.13
Glycosides are widely distributed in nature and play important
Several (b-D-glucopyranosyloxy)quinolines and quinolin-2(1H)-
roles in living organisms. Quinoline glycoalkaloids, in particular (b-
ones were prepared for treatments of chloroquinone-resistant ma-
D-glucopyranosyloxy)quinolines and their quinolin-2(1H)-one ana-
laria,14,15 tuberculosis16 and as anti-allergic agents,17 respectively.
logues, were isolated from different natural sources. These include
larvae, pupae and adults of some wasps (Vespa levisi) and honey
bees (Apis mellifera and others),1 corn kernels2 and Chinese medic-
inal plant Echinops gmelinii (Compositae).3–5 Plants of the Haplo-
phyllum (Rutaceae) genus are especially rich sources of quinoline
alkaloids including glycoalkaloids of furanoquinoline structures.5–7
Quinoline and quinolinone derivatives are metabolized in ani-
mals to hydroxyl derivatives which then become conjugated with
8-(b-D-Glucopyranosyloxy)quinoline inhibits human Na-depen-
dent glucose cotransporter, hSGLT1.18
To assist in unequivocal identification of such conjugated natu-
ral products and metabolites as well as in designing new drugs it is
necessary to have available convenient synthesis. A logical route to
glycosyloxyquinoline derivatives is the formation of glycosidic
linkage from a glycosyl donor and an appropriate hydroxyquino-
line as glycosyl acceptor.19 In comparison with other isomeric
hydroxyquinolines, this task is more challenging for the systems
with a tautomeric equilibrium, namely N-unsubstituted 2-hydroxy
and 4-hydroxyquinolines, and especially 4-hydroxyquinolin-
2(1H)-ones, in which the heterocycle possesses three positions
for the attack of the glucosyl group. With the exception of few early
reports,20 a literature survey revealed that very little work has
been devoted to address this issue.21 This is even more surprising
as some of the above-mentioned natural products still remain
characterized solely on the basis of UV-spectroscopic data.8 As a
part of our continuous interest in the chemistry of quinolinones,22
herein we report selective glucosylation of N-unsubstituted 4-
D-glucuronic acid prior to their excretion. In this connection, b-D-
glucopyranosiduronic acid derivatives of quinoline, quinolin-
2(1H)-one and quinolin-4(1H)-one were isolated from the urine
of rabbits,8 rats9,10 and mice.10
Interesting biochemistry is associated with 8-(b-D-glucopyrano-
syloxy)-4-hydroxy-2-quinolinecarboxylic acid. This highly fluores-
cent compound is a pigment in some eye colour mutants of flies
(Drosophila melanogaster)11 and in the human brunescent catarac-
tous lens nuclei.12 Recently it has been also identified as a natri-
* Corresponding authors. Fax: + 420 57 72 10 172 (S.K.); +386 124 19 220 (J.K.).
E-mail addresses: kafka@ft.utb.cz (S. Kafka), janez.kosmrlj@fkkt.uni-lj.si (J.
Košmrlj).
hydroxyquinolin-2(1H)-ones into 4-(b-
oline-2(1H)-ones.
D-glucopyranosyloxy)quin-
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.01.023

R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
769
2
2a
2b
2c
2d
X
α
-OAc
-OH
α
2. Results and discussion
OAc
O
-Br
AcO
Glycosyl acceptors, substituted 4-hydroxyquinolin-2-(1H)-ones
1b–i, were prepared by known reactions starting from aniline and
three different methoxyanilines with two diethyl malonates, as
shown in Scheme 1.23 Ethyl and phenyl groups were chosen for
R1 substituents as representatives of small alkyl and bulkier aryl
group in the vicinity of the 4-OH reactive centre of substrate 1.
At the fused benzene ring, 6-, 7- or 8-methoxy-functionalized
derivatives (1d–i) were chosen. The methoxy group was selected
because, after deprotection into a phenolic hydroxyl moiety,24 it
could potentially serve as a handle for further functionalization.
Notably, methoxy group accompanies many quinoline alkaloids.4
At the fused benzene ring unsubstituted 4-hydroxyquinolin-
2(1H)-ones (1b,c) and fully unsubstituted compound 1a were also
considered as glycosyl acceptors. 3-Ethyl-4-hydroxy-7-methoxy-
quinolin-2(1H)-one (1e) was chosen to be a model substrate to
identify the method of choice for glycosylation (vide infra).
AcO
X
OAc
-OCCCl3
NH
Chart 1. Glucosyl donors.
oped as mild alternatives, being especially successful if
conducted under phase transfer conditions. In this connection we
first examined glucosylation of 1e with acetobromo-a-D-glucose
2a (1.5 equiv) in biphasic mixture of CH2Cl2 and aqueous Na2CO3
(1.0 equiv) containing (Bu4N)Br (0.4 equiv) as phase transfer cata-
lyst.29 The desired product 3e was isolated in 71% yield (protocol
B, Table 1, entry 2).
Recently, highly effective glycosylation reaction to the phenolic
group using Cs2CO3 and acetobromo-a-D-glucose has been devel-
oped.30 Following this procedure, 4-hydroxyquinolin-2-(1H)-one
1e was treated with an equimolar amount of Cs2CO3 and threefold
With the desired glucosyl acceptors 1 in hand, we decided to
explore the glucosylation with four known glucosyl donors de-
picted in Chart 1. The tetra-O-acetyl-protected glucosyl donors
2a–d were selected over the tetra-O-benzyl analogues because
quinolinone ring is generally sensitive to reduction conditions
and may, as aglycone, potentially be hydrogenated25 during the
excess of acetobromo-a-D-glucose 2a in CH3CN at room tempera-
ture to give 3e in 51% yield (protocol C, Table 1, entry 3). After opti-
mization of these reaction conditions, the use of increased amount
of Cs2CO3 (3 equiv, protocol D, Table 1, entry 4) proved to give the
highest yield (75%) of 3e.
cleavage of the benzyl-protecting groups. Tetra-O-acetyl-
copyranosyl bromide (2a) and b- -glucose pentaacetate 2b were
used as supplied from the commercial source, whereas glucose
tetraacetate 2c26 and tetra-O-acetyl-
-glucopyranosyl trichloro-
acetimidate (2d)27 were prepared by the literature procedures
from b- -glucose pentaacetate 2b.
a-D-glu-
D
Relatively high amounts of acetobromo-a-D-glucose 2a re-
quired in the above experiments prompted us to assess the glu-
cosylation with much cheaper glucose pentaacetate (2b) and
glucose tetraacetate (2c). Although 1-O-acylated glycosyl donors
in combination with catalytic Lewis acid have previously been suc-
cessfully employed for glycosylation with phenols and alcohols,
reaction between 1e and glucose pentaacetate (2b) could be ob-
served in the presence of neither Sc(OTf)3 (15 mol %) and molecu-
lar sieves in toluene31 nor BF3ꢀEt2O (6 equiv) in CH2Cl2 (Table 1,
entries 5 and 6).32 In both instances, the analyses of the reaction
mixtures by thin layer chromatography (TLC) revealed only the
presence of unreacted starting material 1e.
a
-D
D
Major advances in the synthesis of glycosides have been made
by the use of Koenigs–Knorr28 method in which glycosyl halides
are activated by varieties of silver and mercury salts. In our case,
however, attempted 4-O-glucosylation of 1e with acetobromo-
a-
D
-glucose 2a using Ag2O as activating reagent in CH3CN led to
bis-glucosylated product 4e exclusively (protocol A, Table 1, entry
1).
Extensions of the Koenigs–Knorr conditions using glycosyl bro-
mide in the absence of heavy metal compounds have been devel-
One of the attractive approaches for glycosylation involves C-1-
hydroxyl glycosyl donors in which an unprotected anomeric
O
R1
1
R1 R2
Yield (%)
EtO
a
R1 = Et, Ph
OH
–
1a
H
H
H
H
R1
O
EtO
O
1b Et
1c Ph
69
88
R2
R2
NH2
–
–
1d Et 6-OCH3 64
1e Et 7-OCH3 68
1f Et 8-OCH3 62
1g Ph 6-OCH3 71
1h Ph 7-OCH3 89
1i Ph 8-OCH3 35
260 270 °C
N
H
2 5 h
R2 = H
1
2-OCH3
3-OCH3
4-OCH3
a
From a commercial source.
Scheme 1. Structure and source of glycosyl acceptors 1a–i.
OAc
O
R2
R2
7
7
AcO
AcO
OH
8
8
R2
6
6
R1
O
X
1
OAc
1
OAc
5'
5
OAc
5'
2
5
N
2
6'
NH
6'
AcO
3''
6''
4'
+
4'
2
4
2''
AcO
AcO
AcO
AcO
O
O
OAc
OAc
4''
N
H
solvent, aditive
room temperature
1'
1'
O
O
1''
O
O
4
3
3
O
5''
AcO
2'
R1
2'
3'
3'
R1
OAc
OAc
1
–
Protocols A E
3
4
(Tables 1,2)
Scheme 2. Glucosylation of 4-hydroxyquinolin-2-(1H)-ones 1 with glucosyl donors 2. For conditions and results, see Tables 1 and 2. Compounds 3 and 4 are depicted with
the numbering scheme used for 1H and 13C NMR spectra assignment (triple-primed figures are used for C-3-phenyl group, R1 = Ph).

770
R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
Table 1
Analysis of different glucosyl donors 2a–d and the reaction conditions for glucosylation of 1e (Scheme 2)
Entry
2a (equiv)
Protocol
Additive
Solvent
R. timeb (h)
Products (yield)c
Others
3
d
1
2
3
4
5
6
7
8
9
2a (2)
2a (1.5)
2a (3)
2a (3)
2b (1.5)
2b (6)
A
B
C
D
Ag2O (2.5)a
CH3CN
CH2Cl2/water (1:1)
CH3CN
CH3CN
Toluene
CH2Cl2
DMF
CH2Cl2
CH2Cl2
CH3CN
80
68
25
72
48
55
—
4e (52)
Na2CO3 (1),a (Bu4N)Br (0.4)a
Cs2CO3 (1)a
3e (71)
3e (51)
3e (75)
Cs2CO3 (3)a
d
Sc(OTf)3 (0.15),a molecular sieves
BF3ꢀEt2O (6)a
—
—
—
d
d
2c (1)
Ph3P/CBr4 (3/3)a
TMSOTf (7.2)e
2d (1.3)
2d (2.0)
2d (1.3)
2d (1.29)
E
E
E
E
30
19
30
49
3e (31)
3e (42)
1e (33)f
1e (20)f
1e (66)f
1e (50)f
TMSOTf (7.9)e
d
10
11
TMSOTf (7.2)e
—
TMSOTf (7.6)e
1,4-Dioxane
3e (22)
a
b
c
d
e
f
Equiv relative to 1e.
The reactions were carried out at room temperature.
Refers to isolated percent yield of pure product.
No product was detected by TLC.
Mol % relative to 2d.
Recovered starting material.
hydroxyl is exchanged in a dehydration process. From the variety
of dehydrating reagents we decided to test the recently reported
conditions using Appel agents. Under these conditions protected
C-1-hydroxyl sugar is in situ transformed into C-1-bromoderiva-
tive by triphenylphosphine and tetrabromomethane in DMF.33
Our attempts to use this protocol for coupling glucose tetraacetate
(2c) with 1e resulted in complex mixtures of products with no
trace amounts of 3e (Table 1, entry 7). These results are not com-
pletely unexpected as the strongly activated methoxy-substituted
heterocyclic system of 1e may interfere with electrophilic bromine
intermediates produced by Appel agents, for example.
of O-glucosylation in terms of selectivity and the yield of the de-
sired product 3e. This method (protocol D) was therefore selected
to demonstrate the scope at glucosyl acceptors 1a–d,f–i, and the
results are shown in Table 2. In some instances the formation of
glucoside 3 was accompanied by the formation of bis-glucosylated
products 4. This could be suppressed, albeit on the expense of 3, by
decreasing the amount of Cs2CO3 (Table 2, entries 5–10).
Deprotection of acetylated saccharides is usually performed by
strong base, such as NaOH, MeONa, or by organic base, such as
Et3N. As a practical alternative to the inorganic reagents, basic
ion-exchange resin, AmberlystÒ A-26 (OH), has been developed,
allowing the isolation of deprotected saccharide product by filtra-
tion.15 In our case this protocol was not convenient because of
sparing solubility of compounds 5, as determined in the prelimin-
ary experiments. Hence, for deacetylation of compounds 3, we se-
lected Et3N35 in MeOH as a solvent (Scheme 3, Table 3). In a general
procedure a mixture of acetyl derivative 3 and Et3N (5 equiv) in
MeOH was heated at reflux until the starting compound 3 disap-
peared from the reaction mixture, as judged by TLC (Table 3). Dur-
ing the progress of the reaction product 5 precipitated from the
reaction mixture. Volatiles were removed by evaporation and
product 5 was isolated from the residue by crystallization from
MeOH or column chromatography, if necessary.
At the last resort, glycosylation was tested with trichloroace-
timidate method developed by Schmidt et al. in 1980,34 which
has offered excellent efficiency when compared with that of its
predecessors. Glucosylation of 1e with 1.3–2.0 equiv of tetra-O-
acetyl-a-D-glucopyranosyl trichloroacetimidate (2d) under the
promotion of trimethylsilyl trifluoromethanesulfonate (TMSOTf)
was conducted in three different solvents: CH2Cl2, CH3CN and
1,4-dioxane. Whereas the reaction in CH3CN failed completely, this
method provided compound 3e with unacceptably low yields by
using CH2Cl2 or 1,4-dioxane (protocol E, Table 1, entries 8–11). In
these experiments high amounts of starting 1e remained unre-
acted and were recovered. This could also be accounted for by
low reactivity of the hydroxyl group of the heterocycle, which is
probably even decreased by the excess amount of the acid catalyst
employed. No reactions were attempted with reduced loadings of
TMSOTf.
Under these reaction conditions the sugar–aglycone bond
proved not to be completely resistant, as demonstrated by detec-
tion and isolation of 4-hydroxyquinolin-2-(1H)-ones 1f–i (Table 3,
entries 6–9). Alkaline cleavage of phenyl glycosides using MeO-
Na in MeOH has been documented36,37 to proceed by nucleophilic
displacement of the aglycone. It requires a sugar moiety with a
It is seen from the results in Table 1 that acetobromo-a-D-glu-
cose (2a) in combination with Cs2CO3 provided superior results
Table 2
Glucosylation of 4-hydroxyquinolin-2-(1H)-ones 1 with acetobromo-a
-D-glucose (2a) under the promotion of Cs2CO3 (Scheme 2, protocol D)a
Entry
1
R1
R2
Cs2CO3 (equiv)
R. timeb (h)
Products (yield)c
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1f
1g
1h
1h
1i
H
Et
Ph
Et
Et
Ph
Ph
Ph
Ph
Ph
H
H
H
3
3
3
3
3
3
1
3
1
3
60
83
60
61
66
91
48
93
69
95
3b (74)
3b (48)
3c (74)
3d (65)
3f (73)
3g (85)
3h (42)
3h (78)
3i (49)
3i (68)
6-OCH3
8-OCH3
6-OCH3
7-OCH3
7-OCH3
8-OCH3
8-OCH3
4f (14)
4g (15)
4h (20)
4i (18)
10
1i
a
b
c
At room temperature.
Based on TLC analysis.
Refers to isolated percent yield of pure product.

R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
771
R2
R2
6
7
8
3
1
OAc
OH
5'
5
6'
NH
Et3N
NH
4'
1
)
( +
2
AcO
AcO
O
HO
HO
O
MeOH
1'
O
O
O
4
O
–
reflux, 5 38 h
2'
3'
R1
OAc
R1
OH
3
5
Scheme 3. Deacetylation of glucosides 3 into 5 with the numbering scheme used for 1H and 13C NMR spectra assignment (triple-primed figures are used for C-3-phenyl
group, R1 = Ph).
Table 3
Table 4
a
Deprotection of acetylated saccharides 3 (Scheme 3)
Selected proton chemical shifts, JH,H and JC,H
0
0
0
0 0
0
0
0 0 ,H-20 0
0 0,H-100
JC-1
Entry
3
R1
R2
R. timea
Products (yield)b
Other
Compound
dH-1
JH-1 ,H-2
dH-1
JH-1
JC-1 ,H-1
5
3a
3b
3c
3d
3e
3f
3g
3h
3i
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5g
5h
5i
5.27
5.10
4.70
5.08
5.07
5.09
4.69
4.71
4.67
5.01
5.08
4.71
4.70
4.73
5.09
4.77
4.34
4.76
4.71
4.78
4.40
4.32
4.31
7.7
8.0
7.9
8.0
8.1
8.0
7.9
7.9
8.0
8.0
8.0
7.9
7.9
7.9
nd
7.7
7.7
7.9
7.7
7.8
7.7
7.8
7.7
165b
164b
167b
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
5
5
7
24
3
38
4
7
5a (86)
5b (76)
5c (97)
5d (72)
5e (92)
5f (78)
5g (75)
5h (56)
5i (38)
Et
Ph
Et
Et
Et
Ph
Ph
Ph
164b, 166c
164b
164b, 166c
166b, 168c
167b
166b
164b
nd
6-OCH3
7-OCH3
8-OCH3
6-OCH3
7-OCH3
8-OCH3
1f (9)
1g (12)
1h (7)
1i (50)
6.42
6.49
6.18
6.21
6.31
m
m
8.1
8.1
8.2
169b
37
nd
169b
a
nd
Reaction time in h.
Isolated percent yield of pure product.
165b
166b
nd
168b, 168c
168b, 167c
b
162c
165b
nd
neighbouring trans 2-hydroxy group, which after the formation of
intermediate 1,2-epoxide in the next step leads to methyl glyco-
side by nucleophilic attack of MeOH at the anomeric carbon atom.
It has been also documented that this solvolysis is facilitated by the
presence of electron-withdrawing group on the aglycone.36,37 Con-
trary to the above, from the results shown in Table 3 it appears that
the presence of strong electron-donating methoxy group facilitates
the decomposition of quinolinone glycosides, especially in the case
of 3i. Based on the above discussion it can be expected that in 3 the
sugar–C–O bond, and not the O–C–heterocycle bond, is cleaved.
This can be mediated either by MeOH or intramolecularly by
unprotected CH2OH at C-60 of the sugar component. In agreement
with this is the fact that no 4-O-methylated 4-hydroxyquinolin-
2(1H)-one derivatives of 1 were obtained. Unfortunately, we were
not able to isolate the liberated sugar component of this decompo-
sition. To the best of our knowledge, the decomposition of the su-
gar–aglycone bond in 3f–i is the first example in quinolinone
glycosides.
nd
nd
nd
164b
nd
a
In CDCl3 for compounds 3 and 4 and in DMSO-d6 for compounds 5 (nd = not
determined, m = multiplet).
b
From HMBC, ppm 1,
From satellites in 1H NMR, ppm ( 0.1).
c
Structure elucidation and assignments of proton and carbon
resonances of compounds 3–5 were performed by standard two
dimensional NMR techniques. Structural analysis of 4-O-b-D-gluco-
pyranose in compounds 3–5 begun with well-resolved anomeric
proton H-10 chemical shifts found in the range of 4.3–5.3 ppm
(Table 4). In HMBC spectra of 3–5 this proton correlates with C-4
of the quinolinone ring. The position of 4-O-sugar in 4f was also
confirmed by NOE interactions between H-10 and H-5 (Fig. 1). The
large vicinal coupling constants between anomeric H-10 and the
H-20 of 7.7–8.1 Hz indicated their trans-diaxial orientation and con-
firmed b-configuration.38 Chemical shift range 97–104 ppm was
found for the anomeric carbon atom C-10 (Tables 5–7).
It has been documented that geminal coupling constants be-
tween the anomeric carbon and hydrogen in pyranoses can be used
Figure 1. Partial NOESY spectrum of 4f in CDCl3 with the selected atom-numbering
scheme.
for the assignment of anomeric configuration. For
D
-sugars in the
1
4C1 conformation, a JC-1,H-1 ꢁ170 Hz indicates an
a-anomeric su-
gar configuration whereas 1JC-1,H-1 ꢁ160 Hz indicates a b-anomeric
sugar configuration.38 For compounds 3–5 coupling constants
NMR spectra and/or estimated from incompletely suppressed di-
rect correlations between protons and 13C nuclei in HMBC spectra
1
JC-1 ,H-1 of 162–168 Hz were determined from 13C satellites in 1H
0
0

772
R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
Table 5
13C NMR Chemical shifts in ppm for compounds 3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
Aglycone
C-2
C-3
C-4
C-4a
C-5
C-6
C-7
C-8
C-8a
Et
165.5
99.7
165.2
126.7
157.2
117.1
123.3
122.2
130.1
115.7
137.1
13.0
164.6
119.6
157.4
117.4
123.9
122.6
131.1
115.6
137.5
—
164.7
126.5
157.2
117.9
105.2
155.0
119.6
116.9
131.7
13.1
165.9
123.1
157.7
111.1
124.8
111.8
161.4
98.1
162.9
127.7
156.8
117.4
115.2
121.7
109.6
145.4
127.2
12.8
164.0
119.3
156.9
117.8
104.3
155.2
121.3
117.1
132.3b
—
165.2
116.6
157.7
111.2
125.4
112.3
162.2
97.7
162.5
120.5
157.1
117.8
115.9
122.0
110.5
145.2
127.7
—
161.9
114.9
122.73b
122.66b
131.6
116.0
138.4
—
138.9
13.1
139.4
—
18.0
18.0
17.7
18.0
Ph
—
—
128.3
128.3
131.0
132.1
—
—
—
—
128.3
128.3
131.0
132.1b
55.9
128.0
128.1
131.1
132.4
55.4
128.3
128.4
130.8
132.1
56.1
CH3O
—
—
55.6
55.5
56.0
4-O-b-
C-10
C-20
C-30
C-40
C-50
C-60
D-Glucopyranosyl
97.6
70.6
72.3
68.0
72.6
101.3
71.8
72.9
68.3
72.1
98.6
71.5
72.6
67.8
72.0
101.7
71.7
72.9
68.2
72.1
101.3
71.7
72.8
68.2
72.0
101.2
71.8
72.9
68.3
72.1
98.6
71.5
72.5
67.6
72.1
98.5
71.4
72.5
67.7
71.9
98.5
71.4
72.6
67.8
72.0
61.5
61.6
61.2
61.6
61.6
61.6
61.0
61.1
61.2
CH3CO
20.55
20.57
20.57
20.63
169.3
169.4
170.1
170.6
20.51
20.55
20.61
20.73
169.2
169.4
170.3
170.4
20.48
20.53
20.58
20.58
169.2
169.3
170.2
170.4
20.4
20.5
20.6
20.7
169.3
169.4
170.3
170.4
20.4
20.5
20.6
20.7
169.1
169.3
170.2
170.4
20.54
20.55
20.6
20.45
20.47
20.51
20.56
169.2
169.4
170.1
170.4
20.4
20.48
20.53
20.61
20.61
169.2
169.3
170.1
170.3
20.48
20.53
20.6
169.2
169.3
170.1
170.4
20.7
CH3CO
169.2
169.3
170.3
170.5
a
In CDCl3.
Tentative assignment.
b
(Table 4). These values are in agreement with the fact that when a
protons H-10 and H-50, and protons H-100 and H-500, respectively,
as demonstrated in Figure 1.
In conclusion, we have identified a method for selective glu-
cosylation at N-unsubstituted 4-hydroxyquinolin-2-(1H)-ones.
The reactions proceeded stereoselectively with the formation of
1
more electronegative substituent is introduced at C-1 the JC-1,H-1
increases.39
For compounds 4 spectral and analytical data suggested the
presence of the second b-D-glucopyranose moiety. Its anomeric
proton H-100 resonances were found in the shift range 6.2–
6.5 ppm, again with the large vicinal coupling constants between
anomeric H-100 and the H-200 of 8.1–8.2 Hz (Table 4). This second
sugar moiety could be attached either to N-1 atom of the lactam
ring of the heterocycle or to the oxygen atom of its lactim tauto-
meric form. No information of its exact position with respect to
the heterocyclic system could be elucidated from NOESY spectra
(4f in CDCl3, 4i in DMSO-d6) as no correlation was observed be-
tween H-100 and neither the protons of ethyl or phenyl at R1 (in
4f and 4i, respectively) groups, nor the protons of the substituted
fused benzene ring (H-8 in 4f, 8-OCH3 in 4i). Inconclusive informa-
tion was also obtained from HMBC spectra of compounds 4e–i in
which the anomeric H-100 proton correlated with C-2 of the
quinolone ring. In principle this could be expected for both N-
and 2-O-glycosylated isomeric products. The 2,4-bis(2,3,4,6-tetra-
b-glycosidic linkage, as confirmed by NMR. The resulting 4-(b-D-
glucopyranosyloxy)quinolin-2(1H)-ones were formed in good
yields and will be of interest for further investigations towards bio-
logically active compounds.
3. Experimental
3.1. General methods
The melting points were determined on a Kofler block or Gal-
lenkamp apparatus and are uncorrected. The IR spectra were re-
corded on a Perkin–Elmer 421 and 1310 and Mattson 3000
spectrophotometers using samples in potassium bromide disks.
NMR data were collected on a Bruker Avance DPX 300 spectrome-
ter operating at frequencies 300 MHz (1H) and 75 MHz (13C) and
equipped with a 5-mm 1H/13C/31P/19F-QNP probehead or 5-mm in-
verse-detection probe with z-gradient coil for 2D experiments. The
spectra were recorded at 302 K. Chemical shifts are given on the d
scale (ppm) and are referenced to internal Me4Si. Coupling con-
stants (J) are given in hertz. Multiplicities are indicated as follows:
s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and br
(broadened). Structure elucidation and assignments of proton and
carbon resonances were performed by 2D NMR (1H–1H gs-COSY,
1H–13C gs-HSQC and gs-HMBC) spectral analyses. The numbering
used for the assignment of NMR signals is as follows: quinoli-
O-acetyl-b-D-glucopyranosyloxy)quinoline structure of compounds
4 was suggested on the basis of chemical shift range 93–94 ppm for
the anomeric carbon atom C-100 (Table 6). These values are in a
close agreement with the literature data for O-glucosylated pyri-
dine-2-one and related compounds,40 and thus rule out the possi-
bility that the second sugar component is attached to the N-1
nitrogen atom of the quinolinone. The anomeric 13C chemical shift
for the N-glycosylation counterparts (1-N-b-D-glucopyranoses)
would be expected below 80 ppm.40b,41
The b-anomeric configuration at both 2-O- and 4-O-sugar
none skeleton, simple figures; 4-(b-D-glucopyranosyloxy) groups,
components was further confirmed by NOE interactions between

R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
773
Table 6
Table 7
13C NMR Chemical shifts in ppm for compounds 4a
13C NMR Chemical shifts in ppm for compounds 5a
b
4e
4f
4g
4h
4i
5a
Aglycone
5b
5c
5d
5e
5f
5g
5h
5i
Aglycone
C-2
C-3
C-4
C-4a
C-5
C-6
C-7
C-8
C-8a
Et
159.7
117.3
158.2
116.9
124.1
116.7
160.9
106.4
146.9
13.6
158.3
120.7
157.9
123.2
114.7
124.6
109.4
154.4
136.7
13.3
156.5
114.8
156.7
122.6
101.4
156.9
122.7
128.5
141.2
—
158.7
112.8
157.6
116.7
124.4
117.1
161.7
106.3
147.7
—
157.2
115.5
157.7
123.3
115.2
125.0
110.5
154.2
137.4
—
C-2
C-3
C-4
C-4a
C-5
C-6
C-7
C-8
C-8a
Et
163.2 163.1 163.0 162.6 163.6 162.6 162.2 163.0 162.2
99.8 126.2 120.0 126.9 123.0 126.7 121.0 117.1 120.4
161.1 156.7 156.6 156.4 157.1 156.8 156.0 156.6 156.4
114.4 116.3 117.0 116.8 110.1 116.9 117.1 110.5 117.3
122.8 123.7 124.3 105.3 125.3 115.4 105.7 125.6 115.7
121.3 121.4 121.9 154.0 110.2 121.3 154.1 110.3 121.4
131.0 129.6 130.9 119.0 160.5 110.4 119.8 161.2 111.2
b
b
115.1 114.9 115.1 116.3
97.8 145.6 116.3
97.5 145.6
138.6 137.4 138.0 131.9 139.1 127.4 132.5 139.5 128.0
—
—
12.9
17.6
—
—
12.9
17.7
—
13.0
17.4
—
12.8
17.7
—
—
—
—
16.9
—
17.2
—
Ph
128.0
128.0
130.7
131.4
55.6
128.0
128.2
130.8
131.5
55.5
128.2
128.2
130.7
131.3
56.6
Ph
127.5
127.8
131.1
133.4
—
127.1 126.9 127.2
127.3 127.3 127.4
130.9 130.9 130.8
133.4 133.4 133.3
CH3O
55.5
56.5
CH3O
—
—
55.4
55.3
56.1
55.5
55.3
56.2
2-O-b-
C-100
C-200
C-300
C-400
C-500
C-600
D
-Glucopyranosyl
4-O-b-
C-10
C-20
C-30
C-40
C-50
C-60
D
-Glucopyranosyl
99.6 103.9 100.7 103.9 104.0 103.9 101.5 100.5 100.5
93.3
70.7
73.2
68.5
72.2
61.9
93.5
70.6
73.3
68.6
72.3
61.8
94.0
70.5
73.2
68.4
72.3
61.9
93.9
70.5
73.1
68.3
72.2
61.9
94.1
70.4
73.2
68.4
72.4
61.9
73.1
76.2
69.6
77.2
60.8
74.1
76.5
69.7
77.3
60.9
73.9
76.4
69.4
77.2
60.6
74.0
76.4
69.6
77.2
60.9
74.0
76.5
69.7
77.2
60.8
74.1
76.5
69.7
77.3
60.9
73.7
76.2
69.3
77.0
60.5
73.6
76.1
69.2
76.9
60.3
73.7
76.2
69.3
77.0
60.4
a
4-O-b-
C-10
C-20
C-30
C-40
C-50
C-60
D
-Glucopyranosyl
102.0
71.7
In DMSO-d6.
101.7
71.8
72.9
68.2
72.0
99.5
71.5
72.6
67.7
72.1
99.3
71.4
72.6
67.8
71.9
99.5
71.5
72.7
67.8
72.0
61.1
20.7
20.88
20.93
20.98
20.99
21.02
21.02
21.02
168.7
169.2
169.3
169.5
170.18
170.19
170.4
170.7
vents and reagents were used as obtained from the commercial
sources.
72.9
68.3
72.0
61.6
61.5
61.1
20.3
61.1
20.3
3.2. Procedures for the glucosylation of 4-hydroxyquinolin-
2(1H)-ones (1a–i) using acetobromo-a-D-glucose (2a)
CH3CO
20.44
20.55
20.60
20.60
20.64
20.66
20.69
20.72
169.17
169.29
169.32
169.5
170.25
170.27
170.33
170.6
20.49
20.55
20.57
20.59
20.61
20.64
20.66
20.71
169.16
169.31
169.33
169.52
170.23
170.29
170.33
170.65
20.48
20.51
20.55
20.60
20.69
20.72
20.75
168.7
169.3
169.5
170.0
170.1
170.2
170.2
170.3
20.46
20.51
20.54
20.55
20.59
20.64
20.72
168.6
169.2
169.3
169.4
170.17
170.20
170.4
170.6
3.2.1. Protocol A (Table 1, entry 1). Preparation of 3-ethyl-7-
methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyloxy)
quinoline (4e) from 1e and 2a using Ag2O
A mixture of 3-ethyl-7-methoxy-4-hydroxyquinolin-2(1H)-one
(1e, 871 mg, 4.0 mmol), acetobromo- -glucose 2a (3.30 g,
8.0 mmol) and Ag2O (2.32 g, 10 mmol) in CH3CN (40 mL) was stir-
red in dark, at room temperature, for 80 h and then filtered
through 4 layers of filter paper (dense, narrow pores; grade 390).
The filtrate was evaporated to dryness and the residue was crystal-
lized from EtOH, yielding pure 4e (1.84 g, 52%).
D
CH3CO
a
-D
a
In CDCl3.
Tentative assignment.
b
3.2.2. Protocol B (Table 1, entry 2). Preparation of 3-ethyl-7-
methoxy-4-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyloxy)
primed figures; 2-(b-
D
-glucopyranosyloxy) groups, double-primed
quinolin-2(1H)-one (3e) under phase transfer conditions
A mixture of 3-ethyl-7-methoxy-4-hydroxyquinolin-2(1H)-one
figures; C-3-phenyl group, triple-primed figures. Geminal H-6 pro-
tons at the sugar moieties resonating at low field and high field are
assigned as H-6a and H-6b, respectively. Proton-coupling constant
values were determined directly from the spectra after zero filling
and resolution enhancement (Gaussian apodization with suitable
LB and GB). Mass spectra and high-resolution mass spectra were
obtained with a VG-Analytical AutospecQ instrument and Q-TOF
Premier instrument. Data are reported as m/z (relative intensity).
The reactions were monitored by TLC on TLC-CARDS SILICA GEL,
220–440 mesh. Detection involved spraying the chromatogram
with a solution of 17% H2SO4 in water (w/w) containing ammo-
nium molybdate (2.3%) and ceric sulfate (0.9%) (Hanessian dip)
and heating the plate for several minutes at ca 180 °C. For column
chromatography, Fluka Silica Gel 60, 220–440 mesh was used. Ele-
mental analyses (C, H, N) were performed with FlashEA1112 Auto-
matic Elemental Analyzer (Thermo Fisher Scientific Inc.). Optical
rotations were measured in a 1 dm path-length cell on a Jasco
Model DIP-370 polarimeter or Perkin–Elmer 241 MC polarimeter
and the concentrations are given in g/100 mL. Compound 1a, sol-
(1e, 109 mg, 0.5 mmol), acetobromo-a-D-glucose 2a (309 mg,
0.75 mmol), Na2CO3 (82 mg, 0.77 mmol) and (Bu4N)Br (64 mg,
0.2 mmol) was suspended in a mixture of CH2Cl2 (5 mL) and water
(5 mL), and stirred at room temperature for 68 h. The organic layer
was separated and the aqueous layer was extracted with CH2Cl2
(3 ꢂ 20 mL). The combined organic layers were dried over Na2SO4,
filtered and evaporated to dryness. The residue was column chro-
matographed using the mixture of CH2Cl2–MeOH (10:1) as eluent
to give product 3e (193 mg, 71%). For analyses this product was
re-crystallized from the mixture petroleum ether–EtOAc yielding
pure 3e (93 mg, 37%).
3.2.3. Protocol C (Table 1, entry 3). Preparation of 3-ethyl-7-
methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
quinolin-2(1H)-one (3e) using Cs2CO3
A suspension of 3-ethyl-7-methoxy-4-hydroxyquinolin-2(1H)-
one (1e, 110 mg, 0.5 mmol), acetobromo- -glucose 2a (618 mg,
1.50 mmol) and Cs2CO3 (163 mg, 0.5 mmol) in CH3CN (5 mL) was
D-glucopyranosyloxy)
a-D

774
R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
stirred at room temperature for 25 h. Water (10 mL) was added
and the resulting solution was extracted with CH2Cl2
(4 ꢂ 25 mL). The combined organic layers were dried over Na2SO4,
filtered and evaporated to dryness. The residue was column chro-
matographed using the mixture of CH2Cl2–MeOH (20:1) as eluent
to give product 3e, which was re-crystallized from the mixture
petroleum ether–EtOAc affording pure 3e (140 mg, 51%).
from the appropriate solvent, as indicated below. In the case of
deacetylation of compounds 3c,f–i, the resulting crude product
was column chromatographed using the mixture of CH2Cl2–MeOH
(10:1) as eluent to give the corresponding compounds 1f–i and
5c,f–i in sequence, which were pure according to TLC and NMR
spectra. For elemental analysis and optical rotatory power mea-
surements, compounds 5c,f–i were recrystallized from appropriate
solvents, indicated below.
3.2.4. Protocol D (Table 1, entry 4 and Table 2). General
procedure for the preparation of 4-(2,3,4,6-tetra-O-acetyl-b-
glucopyranosyloxy)quinolin-2(1H)-ones 3 using Cs2CO3
D-
3.6. Spectral and analytical data for compounds 3–5
A suspension of the appropriate 4-hydroxyquinolin-2-(1H)-one
1 (4 mmol, Table 1, entry 4 and Table 2), acetobromo- -glucose
3.6.1. 4-(2,3,4,6-Tetra-O-acetyl-b-
quinolin-2(1H)-one (3a)
D-glucopyranosyloxy)-
a-D
2a (4.93 g, 12 mmol) and Cs2CO3 (3.90 g, 12 mmol) in CH3CN
(40 mL) was stirred at room temperature for the time indicated
in Table 1, entry 4 and Table 2. Water (50 mL) was added and
the resulting solution was extracted with CH2Cl2 (7 ꢂ 50 mL). The
combined organic layers were dried over Na2SO4, filtered and
evaporated to dryness. The residue was purified by column chro-
matography (CH2Cl2–MeOH, 20:1) to give O-glucosylated products
3 and in some instances bis-glucosylated compounds 4 as side
products (Table 2). The products were for analyses recrystallized
from the solvents indicated below and the yields of pure products
are given in Table 1, entry 4 and Table 2.
White solid, mp 216–217 °C (petroleum ether–EtOAc); ½a D20
ꢃ
ꢄ72 (c 1.0, CH2Cl2); Rf = 0.17 (25% petroleum ether in EtOAc). IR
(KBr) 3460 (br), 3181, 2890, 1749, 1661, 1611, 1503, 1435, 1376,
1223, 1170, 1072, 1037, 910, 842, 754 cmꢄ1 1H NMR (300 MHz,
.
CDCl3) d 2.04, 2.07, 2.08, 2.12 (4 ꢂ s, 12H, 4 ꢂ CH3CO), 3.95 (ddd,
1H, JH-5 ,H-6b = 2.1 Hz, JH-5 ,H-6a = 5.6 Hz, JH-5 ,H-4 = 10.0 Hz, H-50),
0
0
0
0
0
0
4.18 (dd, 1H, JH-6b ,H-5 = 2.1 Hz, JH-6b ,H-6a = 12.4 Hz, H-6b0), 4.35
0
0
0
0
(dd, 1H, JH-6a ,H-5 = 5.6 Hz, JH-6a ,H-6b = 12.4 Hz, H-6a0), 5.19 (dd,
0
0
0
0
1H, JH-4 ,H-3 = 9.2 Hz, JH-4 ,H-5 = 10.0 Hz, H-40), 5.27 (d, 1H, JH-1 ,H-2
0
0
0
0
0
0
= 7.7 Hz, H-10), 5.37 (dd, 1H, JH-3 ,H-2 = 9.2 Hz, JH-3 ,H-4 = 9.2 Hz,
0
0
0
0
H-30), 5.47 (dd, 1H, JH-2 ,H-1 = 7.7 Hz, JH-2 ,H-3 = 9.2 Hz, H-20), 6.13
(s, 1H, H-3), 7.22 (dd, 1H, JH-6,H-5 = 7.6 Hz, JH-6,H-7 = 7.6 Hz, H-6),
7.36 (d, 1H, JH-8,H-7 = 8.0 Hz, H-8), 7.51 (dd, 1H, JH-7,H-8 = 8.0 Hz,
JH-7,H-6 = 7.6 Hz, H-7), 7.77 (d, 1H, JH-5,H-6 = 7.6 Hz, H-5), 10.27 (br
s, 1H, NH); MS (ESI+) m/z (%): 514.1 ([M+Na]+, 100), 492.2
0
0
0
0
3.3. 2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl trichloro-
acetimidate (2d)27
([M+H]+, 48), 131.1 (25); HRMS (ESI+) calcd for C23H26NO11
þ
To a stirred solution of compound 2c (1.00 g, 2.87 mmol) in dry
CH2Cl2 (7 mL), powdered oven-dried K2CO3 (666 mg, 4.82 mmol)
and trichloroacetonitrile (97%, 0.85 mL, 8.2 mmol) were added at
room temperature. The reaction mixture was stirred for 22 h, fil-
tered and the filtrate was evaporated in vacuo to dryness. The res-
idue was purified by column chromatography (petroleum ether–
EtOAc, 5:3) to give 2d (1.23 g, 87%) as a colourless oil. 1H NMR
spectrum of the product was in agreement with the literature
data.34,42
([M+H]+): 492.1506. Found: 492.1503.
3.6.2. 3-Ethyl-4-(2,3,4,6-tetra-O-acetyl-b-
quinolin-2(1H)-one (3b)
D-glucopyranosyloxy)-
White solid, mp 206–209 °C (MeOH–tert-butyl ethyl ether),
+6 (c 1.0, CHCl3); Rf = 0.41 (25% petroleum ether in EtOAc).
IR (KBr) 3483, 3166, 1755, 1664, 1607, 1500, 1425, 1377, 1250,
1231, 1220, 1159, 1099, 1043, 756 cmꢄ1 1H NMR (300 MHz,
½ ꢃ
a 2D0
.
CDCl3) d 1.22 (t, 3H, J = 7.4 Hz, CH3), 1.94, 2.02, 2.06, 2.16 (4 ꢂ s,
3.4. Protocol E (Table 1, entries 8–11). Preparation of 3-ethyl-7-
12H, 4 ꢂ CH3CO), 2.80 (br q, 2H, J = 7.4 Hz, CH2), 3.62 (ddd, 1H,
0
0
0
0
0
0
methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
D
-glucopyranosyloxy)
JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 5.2 Hz, JH-5 ,H-4 = 9.6 Hz, H-50), 3.98
0
0
0
0
quinolin-2(1H)-one (3e) using tetra-O-acetyl-
a
-D
-
(dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a = 12.3 Hz, H-6b0), 4.23 (dd,
0
0
0
0
glucopyranosyl trichloroacetimidate (2d)
1H, JH-6a ,H-5 = 5.2 Hz, JH-6a ,H-6b = 12.3 Hz, H-6a0), 5.10 (d, 1H,
JH-1 ,H-2 = 8.0 Hz, H-10), 5.20 (dd, 1H, JH-4 ,H-3 = 9.4 Hz, JH-4 ,H-5
0
0
0
0
0
0
0
0
0
0
Into a solution of 3-ethyl-7-methoxy-4-hydroxyquinolin-2(1H)-
one (1e, 439 mg, 2.00 mmol) and trichloroacetimidate 2d (Table 1)
in appropriate dry solvent (6.6 mL/mmol of 2d) indicated in Table
1 TMSOTf (Table 1) was added under argon atmosphere at room
temperature. The reaction mixture was stirred for the time indi-
cated in Table 1 and then the volatiles were evaporated in vacuo
to dryness. The residue was suspended in petroleum ether–EtOAc
(1:3, 10 mL) and the solid was filtered off to give unreacted 1e.
The filtrate was evaporated to dryness and the residue was purified
by column chromatography using petroleum ether–EtOAc (1:3) as
eluent to give pure oily product 3e, which was crystallized
from EtOH. The yields of pure products are listed in Table 1, entries
8–11.
= 9.6 Hz, H-40), 5.30 (dd, 1H, JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4 = 9.4 Hz,
H-30), 5.46 (dd, 1H, JH-2 ,H-1 = 8.0 Hz, JH-2 ,H-3 = 9.4 Hz, H-20), 7.20
(dd, 1H, JH-6,H-5 = 7.7 Hz, JH-6,H-7 = 7.7 Hz, H-6), 7.38 (d, 1H,
JH-8,H-7 = 7.7 Hz, H-8), 7.48 (dd, 1H, JH-7,H-8 = 7.7 Hz, JH-7,H-6
= 7.7 Hz, H-7), 7.86 (d, 1H, JH-5,H-6 = 7.7 Hz, H-5), 11.90 (br s, 1H,
NH); MS (ESI+) m/z (%): 542.2 ([M+Na]+, 100), 520.2 ([M+H]+, 7),
451.2 (25), 353.1 (22), 331.1 (17), 190.1 (46), 109.0 (67); HRMS
0
0
0
0
+
þ
(ESI+) calcd for C25H30NO11 ([M+H] ): 520.1819. Found: 520.1820.
3.6.3. 3-Phenyl-4-(2,3,4,6-tetra-O-acetyl-b-
pyranosyloxy)quinolin-2(1H)-one (3c)
D
-gluco-
White solid, mp 183–190 °C (EtOH); ½a D20
ꢃ
ꢄ23 (c 1.0, CH2Cl2);
Rf = 0.33 (25% petroleum ether in EtOAc), Rf = 0.67 (10% EtOH in
CHCl3). IR (KBr) 3474 (br), 3021, 2957, 1746, 1658, 1600, 1570,
3.5. General procedure for deacetylation of glucosides 3 into 5
(Scheme 3, Table 3)
1496, 1436, 1366, 1254, 1225, 1067, 1040, 909, 760, 704 cmꢄ1
.
1H NMR (300 MHz, CDCl3) d 1.86, 1.95, 1.97, 1.98 (4 ꢂ s, 12H,
0
0
0
0
4 ꢂ CH3CO), 2.99 (ddd, 1H, JH-5 ,H-6b = 2.3 Hz, JH-5 ,H-6a = 4.1 Hz,
JH-5 ,H-4 = 9.7 Hz, H-50), 3.83 (dd, 1H, JH-6b ,H-5 = 2.3 Hz, JH-6b ,H-6a
0
0
0
0
0
0
A mixture of the appropriate compound 3 (1 mmol, Table 3) in
Et3N–MeOH solution (0.5 M, 10 mL) was heated under reflux for
the time indicated in Table 3 (after the first hour of reflux the start-
ing material completely dissolved followed by precipitation of the
product). The reaction mixture was evaporated to dryness to give
crude product 5. Products 5a,b,d,e were purified by crystallization
= 12.4 Hz, H-6b0), 4.04 (dd, 1H, JH-6a ,H-5 = 4.1 Hz, JH-6a ,H-6b
=
0
0
0
0
12.4 Hz, H-6a0), 4.70 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10), 4.92 (dd, 1H,
0
0
JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4 = 9.4 Hz, H-30), 5.02 (dd, 1H, JH-4 ,H-3
=
0
0
0
0
0
0
9.4 Hz, JH-4 ,H-5 = 9.7 Hz, H-40), 5.21 (dd, 1H, JH-2 ,H-1 = 7.9 Hz,
0
0
0
0
JH-2 ,H-3 = 9.4 Hz, H-20), 7.17–7.28 (m, 2H, H-8, H-6), 7.42–7.56
0
0

R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
775
(m, 5H, Ph, H-7), 7.89 (d, 1H, JH-5,H-6 = 8.0 Hz, H-5), 11.90 (br s, 1H,
NH); MS (ESI+) m/z (%): 590.2 ([M+Na]+, 100), 568.2 ([M+H]+, 40),
N, 2.55; MS (ESI+) m/z (%): 572.2 ([M+Na]+, 40), 550.2 ([M+H]+,
50), 331.1 (28), 220.1 (77), 214.1 (100), 158.0 (47); HRMS (ESI+)
calcd for C26H32NO12 ([M+H]+): 550.1925. Found: 550.1920.
þ
þ
238.1 (44), 236.1 (82); HRMS (ESI+) calcd for C29H30NO11
([M+H]+): 568.1819. Found: 568.1822.
3.6.7. 3-Phenyl-6-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
D-gluco-
3.6.4. 3-Ethyl-6-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
pyranosyloxy)quinolin-2(1H)-one (3d)
D-gluco-
pyranosyloxy)quinolin-2(1H)-one (3g)
White solid, mp 204–205 °C (petroleum ether–EtOAc); ½a D20
ꢄ26
ꢃ
White solid, mp 242–245 °C (MeOH–tert-butyl ethyl ether);
+9 (c 1.0, CHCl3); Rf = 0.31 (25% petroleum ether in EtOAc).
IR (KBr) 3482 (br), 3151, 1751, 1656, 1624, 1504, 1420, 1372,
1257, 1224, 1069, 1039, 907, 876, 592 cmꢄ1 1H NMR (300 MHz,
(c 1.0, CH2Cl2); Rf = 0.37 (25% petroleum ether in EtOAc). IR (KBr)
½ ꢃ
a 2D0
3482 (br), 3172, 2941, 1753, 1659, 1626, 1497, 1445, 1369, 1280,
1219, 1181, 1086, 1066, 1040, 907, 706 cmꢄ1 1H NMR (300 MHz,
.
.
CDCl3) d 1.81, 1.95, 1.96, 2.01 (4 ꢂ s, 12H, 4 ꢂ CH3CO), 2.92 (ddd,
CDCl3) d 1.22 (t, 3H, J = 7.4 Hz, CH3), 1.93, 2.02, 2.05, 2.14 (4 ꢂ s,
1H, JH-5 ,H-6b = 2.3 Hz, JH-5 ,H-6a = 3.9 Hz, JH-5 ,H-4 = 9.8 Hz, H-50),
0
0
0
0
0
0
0
0
12H, 4 ꢂ CH3CO), 2.80 (m, 1H, CH2), 3.64 (ddd, 1H, JH-5 ,H-6b
3.82 (dd, 1H, JH-6b ,H-5 = 2.3 Hz, JH-6b ,H-6a = 12.5 Hz, H-6b0), 3.88
0
0
0
0
= 2.4 Hz, JH-5 ,H-6a = 5.2 Hz, JH-5 ,H-4 = 9.6 Hz, H-50), 3.86 (s, 3H,
0
0
0
0
0
0
0
0
(s, 3H, CH3O), 4.10 (dd, 1H, JH-6a ,H-5 = 3.9 Hz, JH-6a ,H-6b = 12.5 Hz,
CH3O), 3.94 (dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a = 12.3 Hz, H-6b0),
0
0
0
0
H-6a0), 4.69 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10), 4.92 (dd, 1H, JH-3 ,H-2
0
0
0
0
4.28 (dd, 1H, JH-6a ,H-5 = 5.2 Hz, JH-6a ,H-6b = 12.3 Hz, H-6a0), 5.08
0
0
0
0
= 9.4 Hz, JH-3 ,H-4 = 9.5 Hz, H-30), 5.04 (dd, 1H, JH-4 ,H-3 = 9.5 Hz,
0
0
0
0
(d, 1H, JH-1 ,H-2 = 8.0 Hz, H-10), 5.20 (dd, 1H, JH-4 ,H-3 = 9.4 Hz,
0
0
0
0
JH-4 ,H-5 = 9.8 Hz, H-40), 5.23 (dd, 1H, JH-2 ,H-3 = 9.4 Hz, JH-2 ,H-1
0
0
0
0
0
0
JH-4 ,H-5 = 9.6 Hz, H-40), 5.30 (dd, 1H, JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4
=
0
0
0
0
0
0
= 7.9 Hz, H-20), 7.08 (dd, 1H, JH-7,H-5 = 2.7 Hz, JH-7,H-8 = 8.9 Hz, H-
7), 7.15 (d, 1H, JH-8,H-7 = 8.9 Hz, H-8), 7.31 (d, 1H, JH-5,H-7 = 2.7 Hz,
H-5), 7.40–7.54 (m, 5H, Ph), 12.04 (br s, 1H, NH). Anal. Calcd for
C30H31NO12: C, 60.30; H, 5.23; N, 2.34. Found: C, 60.42; H, 5.23;
N, 2.21; MS (ESI+) m/z (%): 620.2 ([M+Na]+, 41), 598.2 ([M+H]+,
9.4 Hz, H-30), 5.48 (dd, 1H, JH-2 ,H-1 = 8.0 Hz, JH-1 ,H-3 = 9.4 Hz, H-
20), 7.12 (dd, 1H, JH-7,H-5 = 2.7 Hz, JH-7,H-8 = 8.9 Hz, H-7), 7.32 (d,
1H, JH-8,H-7 = 8.9 Hz, H-8), 7.34 (d, 1H, JH-5,H-7 = 2.7 Hz, H-5), 12.06
(br s, 1H, 1H). Anal. Calcd for C26H31NO12: C, 56.83; H, 5.69; N,
2.55. Found: C, 56.87; H, 5.76; N, 2.53; MS (ESI+) m/z (%): 572.2
([M+Na]+, 20), 550.2 ([M+H]+, 12), 476.1 (22), 451.2 (25), 220.1
(89), 158.0 (65), 149.0 (89), 141.0 (100); HRMS (ESI+) calcd for
0
0
0
0
63), 268.1 (100); HRMS (ESI+) calcd for C30H32NO12 ([M+H]+):
þ
598.1925. Found: 598.1950.
C26H32NO12 ([M+H]+): 550.1925. Found: 550.1942.
þ
3.6.8. 3-Phenyl-7-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
D-gluco-
pyranosyloxy)quinolin-2-(1H)-one (3h)
3.6.5. 3-Ethyl-7-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
pyranosyloxy)quinolin-2(1H)-one (3e)
D-gluco-
White solid, mp 174–177 °C (benzene–hexane); ½a D20
ꢄ30 (c 1.0,
ꢃ
CH2Cl2); Rf = 0.25 (25% petroleum ether in EtOAc). IR (KBr) 3470
White solid, mp 231–233 °C (EtOH), ½a D20
ꢃ
0 (c 1.0, CHCl3);
Rf = 0.21 (25 % petroleum ether in EtOAc); IR (KBr) 3483 (br),
(br), 2940, 1753, 1627, 1511, 1445, 1379, 1366, 1254, 1232,
1067, 1034, 907, 791, 702 cmꢄ1 1H NMR (300 MHz, CDCl3) d
.
3163, 2969, 1750, 1659, 1571, 1512, 1379, 1252, 1221, 1153,
1.88, 1.95, 1.97, 1.99 (4 ꢂ s, 12H, 4 ꢂ CH3CO), 2.97 (ddd, 1H,
1096, 1069, 1036, 906 cmꢄ1 1H NMR (300 MHz, CDCl3) d 1.21 (t,
.
JH-5 ,H-6b = 2.5 Hz, JH-5 ,H-6a = 3.9 Hz, JH-5 ,H-4 = 9.7 Hz, H-50), 3.79 (s,
0
0
0
0
0
0
3H, J = 7.3 Hz, CH3), 1.96, 2.02, 2.06, 2.15 (4 ꢂ s, 12H, 4 ꢂ CH3CO),
0
0
0
0
3H, CH3O), 3.82 (dd, 1H, JH-6b ,H-5 = 2.5 Hz, JH-6b ,H-6a = 12.4 Hz, H-
0
0
2.76 (br q, 2H, J = 6.9 Hz, CH2), 3.62 (ddd, 1H, JH-5 ,H-6b = 2.0 Hz,
6b0), 4.04 (dd, 1H, JH-6a ,H-5 = 3.9 Hz, JH-6a ,H-6b = 12.4 Hz, H-6a0),
0
0
0
0
JH-5 ,H-6a = 5.1 Hz, JH-5 ,H-4 = 9.5 Hz, H-50), 3.89 (s, 3H, CH3O), 3.99
0
0
0
0
4.71 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10), 4.91 (dd, 1H, JH-3 ,H-2 = 9.4 Hz,
0
0
0
0
= 12.2 Hz, H-6a0), 4.23 (dd,
H-6b0
a0,H-50
a0
,
(dd, 1H, JH-6
= 2.0 Hz, JH-6
JH-3 ,H-4 = 9.5 Hz, H-30), 5.03 (dd, 1H, JH-3 ,H-4 = 9.5 Hz, JH-4 ,H-5
0
0
0
0
0
0
1H, JH-6b ,H-5 = 5.1 Hz, JH-6b ,H-6 = 12.2 Hz, H-6b0), 5.07 (d, 1H,
0
0
0
a0
= 9.7 Hz, H-40), 5.19 (dd, 1H, JH-2 ,H-1 = 7.9 Hz, JH-2 ,H-3 = 9.4 Hz, H-
20), 6.71 (d, 1H, JH-8,H-6 = 2.4 Hz, H-8), 6.80 (dd, 1H, JH-6,H-8
= 2.4 Hz, JH-6,H-5 = 9.0 Hz, H-6), 7.35–7.52 (m, 5H, Ph), 7.78 (d, 1H,
JH-5,H-6 = 9.0 Hz, H-5), 12.09 (br s, 1H, NH). Anal. Calcd for
C30H31NO12: C, 60.30; H, 5.23; N, 2.34. Found: C, 60.31; H, 5.21;
N, 2.31; MS (ESI+) m/z (%): 620.2 ([M+Na]+, 9), 598.2 ([M+H]+,
0
0
0
0
JH-1 ,H-2 = 8.1 Hz, H-10), 5.19 (dd, 1H, JH-3 ,H-4 = 9.4 Hz, JH-4 ,H-5
=
0
0
0
0
0
0
9.5 Hz, H-40), 5.29 (dd, 1H, JH-3 ,H-2 = 9.3 Hz, JH-3 ,H-4 = 9.4 Hz, H-
0
0
0
0
30), 5.44 (dd, 1H, JH-2 ,H-1 = 8.1 Hz, JH-2 ,H-3 = 9.3 Hz, H-20), 6.79
(dd, 1H, JH-6,H-8 = 2.3 Hz, JH-6,H-5 = 9.0 Hz, H-6), 6.85 (d, 1H, JH-8,H-6
= 2.3 Hz, H-8), 7.76 (d, 1H, JH-5,H-6 = 9.0 Hz, H-5), 12.21 (br s, 1H,
NH). Anal. Calcd for C26H31NO12: C, 56.83; H, 5.69; N, 2.55. Found:
C, 56.71; H, 5.65; N, 2.52; MS (ESI+) m/z (%): 572.2 ([M+Na]+, 10),
550.2 ([M+H]+, 52), 331.1 (35), 220.1 (100), 214.1 (32); HRMS
0
0
0
0
60), 268.1 (100); HRMS (ESI+) calcd for C30H32NO12 ([M+H]+):
598.1925. Found: 598.1926.
þ
+
þ
(ESI+) calcd for C26H32NO12 ([M+H] ): 550.1925. Found: 550.1916.
3.6.9. 3-Phenyl-8-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
D-gluco-
pyranosyloxy)quinolin-2(1H)-one (3i)
3.6.6. 3-Ethyl-8-methoxy-4-(2,3,4,6-tetra-O-acetyl-b-
pyranosyloxy)quinolin-2(1H)-one (3f)
D
-gluco-
White solid, mp 103–106 °C (cyclohexane), ½a D20
ꢄ35 (c 1.0,
ꢃ
White solid, mp 89–95 °C (benzene–hexane); ½a D20
ꢃ
ꢄ6 (c 1.0,
CHCl3); Rf = 0.31 (25% petroleum ether in EtOAc). IR (KBr) 3468
(br), 2940, 1758, 1643, 1579, 1501, 1484, 1446, 1366, 1231,
CH2Cl2); Rf = 0.35 (25% petroleum ether in EtOAc). IR (KBr) 3485
1067, 1042, 905, 779, 738, 701 cmꢄ1 1H NMR (300 MHz, CDCl3) d
.
(br), 2966, 2936, 1757, 1648, 1614, 1579, 1490, 1369, 1223,
1161, 1064, 1041, 906, 777, 740 cmꢄ1 1H NMR (300 MHz, CDCl3)
.
1.89, 1.96, 1.97, 2.01 (4 ꢂ s, 12H, 4 ꢂ CH3CO), 2.99 (ddd, 1H,
JH-5 ,H-6b = 2.3 Hz, JH-5 ,H-6a = 4.2 Hz, JH-5 ,H-4 = 9.6 Hz, H-50), 3.83
0
0
0
0
0
0
d 1.17 (t, 3H, J = 7.4 Hz, CH3), 1.97, 2.02, 2.05, 2.15 (4 ꢂ s, 12H,
(dd, 1H, JH-6b ,H-5 = 2.3 Hz, JH-6b ,H-6a = 12.4 Hz, H-6b0), 3.98 (s, 3H,
0
0
0
0
0
0
4 ꢂ CH3CO), 2.75 (q, 2H, J = 7.4 Hz, CH2), 3.61 (ddd, 1H, JH-5 ,H-4
CH3O), 4.03 (dd, 1H, JH-6a ,H-5 = 4.2 Hz, JH-6a ,H-6b = 12.4 Hz, H-6a0),
= 9.4 Hz, JH-5 ,H-6b = 2.5 Hz, JH-5 ,H-6a = 5.1 Hz, H-50), 3.97 (s, 3H,
0
0
0
0
0
0
0
0
4.67 (d, 1H, JH-1 ,H-2 = 8.0 Hz, H-10), 4.91 (dd, 1H, JH-3 ,H-2 = 9.4 Hz,
CH3O), 3.99 (dd, 1H, JH-6b ,H-5 = 2.5 Hz, JH-6b ,H-6a = 12.3 Hz, H-6b0),
0
0
0
0
0
0
0
0
JH-3 ,H-4 = 9.4 Hz, H-30), 5.01 (dd, 1H, JH-3 ,H-4 = 9.4 Hz, JH-4 ,H-5
4.22 (dd, 1H, JH-6a ,H-5 = 5.1 Hz, JH-6a ,H-6b = 12.3 Hz, H-6a0), 5.09
0
0
0
0
0
0
0
0
0
0
= 9.6 Hz, H-40), 5.19 (dd, 1H, JH-2 ,H-1 = 8.0 Hz, JH-2 ,H-3 = 9.4 Hz, H-
20), 7.00 (d, 1H, JH-7,H-6 = 8.0 Hz, H-7), 7.15 (dd, 1H, JH-6,H-7
= 8.0 Hz, JH-6,H-5 = 8.0 Hz, H-6), 7.38–7.52 (m, 6H, H-5, Ph), 9.17
(br s, 1H, NH). Anal. Calcd for C30H31NO12: C, 60.30; H, 5.25; N,
2.34. Found: C, 60.20; H, 5.27; N, 2.13; MS (ESI+) m/z (%): 620.2
([M+Na]+, 12), 598.2 ([M+H]+, 6), 268.1 (100); HRMS (ESI+) calcd
(d, 1H, JH-1 ,H-2 = 8.0 Hz, H-10), 5.19 (dd, 1H, JH-4 ,H-3 = 9.4 Hz,
0
0
0
0
0
0
0
0
JH-4 ,H-5 = 9.4 Hz, H-40), 5.29 (dd, 1H, JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4
0
0
0
0
0
0
= 9.4 Hz, H-30), 5.44 (dd, 1H, JH-2 ,H-1 = 8.0 Hz, JH-2 ,H-3 =9.4 Hz, H-
20), 6.95 (dd, 1H, JH-7,H-5 = 1.0 Hz, JH-7,H-6 = 8.1 Hz, H-7), 7.11 (dd,
1H, JH-6,H-5 = 8.1 Hz, JH-6,H-7 = 8.1 Hz, H-6), 7.43 (dd, 1H, JH-5,H-7
= 1.0 Hz, JH-5,H-6 = 8.1 Hz, H-5), 9.14 (s, 1H, NH). Anal. Calcd for
C26H31NO12: C, 56.83; H, 5.69; N, 2.55. Found: C, 56.95; H, 5.70;
0
0
0
0
for C30H32NO12 ([M+H]+): 598.1925. Found: 598.1921.
þ

776
R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
3.6.10. 3-Ethyl-7-methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b-
D
-
H-8). Anal. Calcd for C44H49NO21: C, 56.96; H, 5.32; N, 1.51. Found:
C, 56.59; H, 5.33; N, 1.45.
glucopyranosyloxy)quinoline (4e)
White solid, mp 189–196 °C (petroleum ether–EtOAc), ½a D20
ꢃ
+10
(c 0.5, CHCl3); Rf = 0.77 (5% MeOH in CH2Cl2). IR (KBr) 3458, 2969,
3.6.13. 3-Phenyl-7-methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b-D-
1754, 1623, 1580, 1503, 1377, 1348, 1230, 1164, 1065, 1055, 1038,
glucopyranosyloxy)quinoline (4h)
907, 835, 601 cmꢄ1
.
1H NMR (300 MHz, CDCl3) d 1.08 (t, 3H,
White solid, mp 110–116 °C (MeOH–EtOAc); ½a D20
ꢄ6 (c 1.0,
ꢃ
J = 7.2 Hz, CH3), 1.90, 1.98, 2.02, 2.02, 2.05, 2.05, 2.06, 2.15 (8 ꢂ s,
CH2Cl2); Rf = 0.64 (25% petroleum ether in EtOAc). IR (KBr) 3476
24H, 8 ꢂ CH3CO), 2.75 (q, 2H, J = 7.4 Hz, CH2CH3), 3.54 (ddd, 1H,
(br), 2961, 1758, 1622, 1576, 1502, 1435, 1370, 1344, 1224,
JH-5 ,H-6b = 2.5 Hz, JH-5 ,H-6a = 5.1 Hz, JH-5 ,H-4 = 9.5 Hz, H-50), 3.90
1232, 1067, 1040, 907, 701, 600 cmꢄ1 1H NMR (300 MHz, CDCl3)
.
0
0
0
0
0
0
(dd, 1H, JH-6b ,H-5 = 2.5 Hz, JH-6b ,H-6a = 12.4 Hz, H-6b0), 3.92 (s, 3H,
d
1.83, 1.85, 1.95, 1.97, 1.97, 1.97, 2.04, 2.04 (8 ꢂ s, 24H,
0
0
0
0
00
00
00
00
0
0
0
0
CH3O), 4.07 (ddd, 1H, JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 4.8 Hz,
8 ꢂ CH3CO), 3.05 (ddd, 1H, JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 4.0 Hz,
JH-5 ,H-4 = 9.9 Hz, H-500), 4.18 (dd, 1H, JH-6b ,H-5 = 2.4 Hz,
JH-5 ,H-4 = 9.8 Hz, H-50), 3.77 (dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a
00
00
00
00
0
0
0
0
0
0
JH-6b
= 12.4 Hz, H-6b00), 4.20 (dd, 1H, JH-6a ,H-5 = 5.1 Hz,
= 12.4 Hz, H-6b0), 3.95 (s, 3H, CH3O), 4.04 (ddd, 1H, JH-5 ,H-6b
0
0
00
00
00,H-6a00
JH-6a ,H-6b = 12.4 Hz, H-6a0), 4.29 (dd, 1H, JH-6a ,H-5 = 4.8 Hz,
= 2.3 Hz, JH-5 ,H-6a = 4.7 Hz, JH-5 ,H-4 = 10.0 Hz, H-500), 4.05 (dd,
0
0
00
00
00
00
00
00
JH-6a ,H-6b = 12.4 Hz, H-6a00), 5.01 (d, 1H, JH-1 ,H-2 = 8.0 Hz, H-10),
1H, JH-6a ,H-5 = 4.0 Hz, JH-6a ,H-6b = 12.4 Hz, H-6a0), 4.18 (dd, 1H,
00
00
0
0
0
0
0
0
5.19 (dd, 1H, JH-4 ,H-3 = 9.3 Hz, JH-4 ,H-5 = 9.5 Hz, H-40), 5.20–5.27
JH-6b ,H-5 = 2.3 Hz, JH-6b ,H-6a = 12.3 Hz, H-6a00), 4.27 (dd, 1H,
0
0
0
0
00
00
00
00
(m, 1H, H-400), 5.28 (dd, 1H, JH-3 ,H-2 = 9.3 Hz, JH-3 ,H-4 = 9.3 Hz, H-
JH-6a ,H-5 = 4.7 Hz, JH-6a ,H-6b = 12.3 Hz, H-6a00), 4.70 (d, 1H, JH-1 ,H-2
0
0
0
0
00
00
00
00
0
0
30), 5.37–5.49 (m, 2H, H-200, H-300), 5.45 (dd, 1H, JH-2 ,H-1 = 8.0 Hz,
= 7.9 Hz, H-10), 4.92 (dd, 1H, JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4 = 9.6 Hz,
0
0
0
0
0
0
JH-2 ,H-3 = 9.3 Hz, H-20), 6.42 (m, 1H, H-100), 7.02 (dd, 1H, JH-6,H-8
= 2.5 Hz, JH-6,H-5 = 9.2 Hz, H-6), 7.12 (d, 1H, JH-8,H-6 = 2.5 Hz, H-8),
7.95 (d, 1H, JH-5,H-6 = 9.2 Hz, H-5). Anal. Calcd for C40H49NO21: C,
54.61; H, 5.61; N, 1.59. Found: C, 54.50; H, 5.62; N, 1.66; MS
(ESI+) m/z (%): 880.3 ([M+H]+, 100), 550.2 (61), 331.1 (23); HRMS
H-30), 5.03 (dd, 1H, JH-4 ,H-3 = 9.6 Hz, JH-4 ,H-5 = 9.8 Hz, H-40), 5.08
0
0
0
0
0
0
(dd, 1H, JH-2 ,H-1 = 8.1 Hz, JH-2 ,H-3 = 9.2 Hz, H-200), 5.14 (dd, 1H,
00
00
00
00
JH-4 ,H-3 = 9.2 Hz, JH-4 ,H-5 = 10.0 Hz, H-400), 5.21 (dd, 1H, JH-2 ,H-1
=
00
00
00
00
0
0
7.9 Hz, JH-2 ,H-3 = 9.4 Hz, H-20), 5.28 (dd, 1H, JH-3 ,H-2 = 9.2 Hz,
0
0
00
00
JH-3 ,H-4 = 9.2 Hz, H-300), 6.21 (d, 1H, JH-1 ,H-2 = 8.1 Hz, H-100), 7.08
(dd, 1H, JH-6,H-8 = 2.5 Hz, JH-6,H-5 = 9.1 Hz, H-6), 7.15 (d, 1H, JH-8,H-6
= 2.5 Hz, H-8), 7.31–7.38 (m, 2H, Ph), 7.38–7.47 (m, 3H, Ph), 7.98
(d, 1H, JH-5,H-6 = 9.1 Hz, H-5); MS (ESI+) m/z (%): 950.3 ([M+Na]+,
100), 928.3 ([M+H]+, 23), 701.2 (11); HRMS (ESI+) calcd for
00
00
00
00
+
þ
(ESI+) calcd for C40H50NO21 ([M+H] ): 880.2875. Found: 880.2850.
3.6.11. 3-Ethyl-8-methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyloxy)quinoline (4f)
C44H50NO21 ([M+H]+): 928.2875. Found: 928.2895.
þ
White solid, mp 100–104 °C (benzene–hexane), ½a D20
ꢃ
+3 (c 1.0,
CHCl3); Rf = 0.61 (25% petroleum ether in EtOAc). IR (KBr) 3451,
2966, 2937, 1757, 1620, 1607, 1504, 1371, 1230, 1166, 1064,
1040, 909, 766, 600 cm-1. 1H NMR (300 MHz, CDCl3) d 1.09 (t,
J = 7.4 Hz, 3H, CH3), 1.92, 1.97, 1.99, 2.02, 2.05, 2.05, 2.07, 2.15
(8 ꢂ s, 24H, 8 ꢂ CH3CO), 2.79 (m, 2H, CH2), 3.54 (ddd, 1H,
3.6.14. 3-Phenyl-8-methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyloxy)quinoline (4i)
White solid, mp 103–105 °C (MeOH); ½a D20
ꢄ14 (c 1.0, CHCl3);
ꢃ
Rf = 0.53 (25% petroleum ether in EtOAc); IR (KBr) 3482 (br),
JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 4.9 Hz, JH-5 ,H-4 = 9.7 Hz, H-50), 3.92
2961, 2942, 1758, 1619, 1498, 1425, 1369, 1229, 1167, 1066,
0
0
0
0
0
0
1039, 906, 700, 599 cmꢄ1 1H NMR (300 MHz, CDCl3) d 1.82, 1.84,
.
(dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a = 12.4 Hz, H-6b0), 4.02 (s, 3H,
0
0
0
0
1.95, 1.96, 1.97, 1.98, 2.01, 2.04 (8 ꢂ s, 24H, 8 ꢂ CH3CO), 3.01
00
00
00
00
CH3O), 4.07 (ddd, 1H, JH-5 ,H-6b = 2.5 Hz, JH-5 ,H-6a = 4.9 Hz,
JH-5 ,H-4 = 10.1 Hz, H-500), 4.17 (dd, 1H, JH-6b
= 2.5 Hz,
0
0
0
0
0
0
(ddd, 1H, JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 4.0 Hz, JH-5 ,H-4 = 9.8 Hz, H-
00,H-500
00
00
50), 3.77 (dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a = 12.3 Hz, H-6b0),
JH-6b
= 12.4 Hz, H-6b00), 4.19 (dd, 1H, JH-6a ,H-5 = 4.9 Hz,
0
0
0
0
0
0
00,H-6a00
4.02 (dd, 1H, JH-6a ,H-5 = 4.0 Hz, JH-6a ,H-6b = 12.3 Hz, H-6a0), 4.04 (s,
JH-6b ,H-6a = 12.4 Hz, H-6a0), 4.26 (dd, 1H, JH-6a ,H-5 = 4.9 Hz,
0
0
0
0
0
0
00
00
JH-6a ,H-6b = 12.4 Hz, H-6a00), 5.08 (d, 1H, JH-1 ,H-2 = 8.0 Hz, H-10),
00
00
00
00
3H, CH3O), 4.04 (ddd, 1H, JH-5 ,H-6b = 2.4 Hz, JH-5 ,H-6a = 4.7 Hz,
00
00
0
0
JH-5 ,H-4 = 9.6 Hz, H-500), 4.16 (dd, 1H, JH-6b ,H-5 = 2.4 Hz, JH-6b ,H-6a
5.19 (dd, 1H, JH-4 ,H-3 = 9.3 Hz, JH-4 ,H-5 = 9.7 Hz, H-40), 5.23 (m, 1H,
00
00
00
00
00
00
0
0
0
0
= 12.3 Hz, H-6b00), 4.25 (dd, 1H, JH-6a ,H-5 = 4.7 Hz, JH-6a ,H-6a
H-400), 5.29 (dd, 1H, JH-3 ,H-2 = 9.3 Hz, JH-3 ,H-4 = 9.3 Hz, H-30), 5.43
a00
00
00
00
0
0
0
0
= 12.3 Hz, H-6a00), 4.73 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10), 4.92 (dd,
(m, 2H, H-200, H-300), 5.46 (dd, 1H, JH-2 ,H-1 = 8.0 Hz, JH-2 ,H-3
9.3 Hz, H-20), 6.49 (m, 1H, H-100), 7.01 (dd, 1H, JH-7,H-5 = 1.2 Hz,
JH-7,H-6 = 7.8 Hz, H-7), 7.30 (dd, 1H, JH-6,H-5 = 7.8 Hz, JH-6,H-7
=
0
0
0
0
0
0
1H, JH-3 ,H-2 = 9.4 Hz, JH-3 ,H-4 = 9.6 Hz, H-30), 5.02 (dd, 1H, JH-4 ,H-3
0
0
0
0
0
0
= 9.6 Hz, JH-4 ,H-5 = 9.8 Hz, H-40), 5.11 (dd, 1H, JH-2 ,H-1 = 8.2 Hz,
0
0
00
00
=
JH-2 ,H-3 = 9.3 Hz, H-200), 5.13 (dd, 1H, JH-4 ,H-3 = 9.3 Hz, JH-4 ,H-5
00
00
00
00
00
00
8.4 Hz, H-6), 7.63 (dd, 1H, JH-5,H-7 = 1.2 Hz, JH-5,H-6 = 8.4 Hz, H-5).
Anal. Calcd for C40H49NO21: C, 54.61; H, 5.61; N, 1.59. Found: C,
54.22; H, 5.52; N, 1.58; MS (ESI+) m/z (%): 902.3 ([M+Na]+, 15),
880.3 ([M+H]+, 100), 550.2 (26); HRMS (ESI+) calcd for
= 9.6 Hz, H-400), 5.20 (dd, 1H, JH-2 ,H-1 = 7.9 Hz, JH-2 ,H-3 = 9.4 Hz,
0
0
0
0
H-20), 5.31 (dd, 1H, JH-3 ,H-2 = 9.3 Hz, JH-3 ,H-4 = 9.3 Hz, H-300),
00
00
00
00
6.31 (d, 1H, JH-1 ,H-2 = 8.2 Hz, H-100), 7.08 (dd, 1H, JH-7,H-5 = 1.2 Hz,
JH-7,H-6 = 7.9 Hz, H-7), 7.32–7.47 (m, 6H, H-6, Ph), 7.68 (dd, 1H,
00
00
C40H50NO21 ([M+H]+): 880.2875. Found: 880.2901.
þ
JH-5,H-7 = 1.2 Hz, JH-5,H-6 = 8.4 Hz, H-5). Anal. Calcd for C44H49NO21
:
C, 56.96; H, 5.32; N, 1.51. Found: C, 56.79; H, 5.39; N, 1.50; MS
(ESI+) m/z (%): 950.3 ([M+Na]+, 33), 928.3 ([M+H]+, 39), 598.2
(100); HRMS (ESI+) calcd for C44H49NO21Na+ ([M+Na]+):
950.2695. Found: 950.2660.
3.6.12. 3-Phenyl-6-methoxy-2,4-bis(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyloxy)quinoline (4g)
White solid, mp 68–71 °C (benzene–cyclohexane), Rf = 0.72
(25% petroleum ether in EtOAc); IR (KBr) 3460, 2961, 2942, 2853,
1755, 1622, 1369, 1230, 1067, 1040, 907, 702, 600 cmꢄ1. Proton
resonances are tentatively assigned as follows: 1H NMR
(300 MHz, CDCl3) d 1.96, 1.96, 1.97, 2.02, 2.03, 2.04, 2.08, 2.09
(8 ꢂ s, 24H, 8 ꢂ CH3CO), 2.98 (ddd, 1H, J = 2.3, 4.0, 10.0 Hz, H-50),
3.76 (dd, 1H, J = 2.3, 12.4 Hz, H-6b0), 3.94 (s, 3H, CH3O), 4.02
(ddd, 1H, J = 2.4, 4.8, 10.0 Hz, H-500), 4.08–4.19 (m, 2H, H-6b00, H-
3.6.15. 4-(b-D-Glucopyranosyloxy)quinolin-2(1H)-one (5a)
White solid, mp 265–268 °C (MeOH); ½a D20
ꢄ63 (c 1.0, DMF);
ꢃ
Rf = 0.70 (EtOH). IR (KBr) 3287 (br), 3226, 2907, 1647, 1613,
1560, 1501, 1477, 1420, 1363, 1229, 1166, 1109, 1069, 1027,
1012, 869, 759 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 3.14–3.56
.
(m, 5H, H-20, H-30, H-40, H-50, H-6b0), 3.68–3.76 (m, 1H, H-6b0),
6a0), 4.21–4.31 (m, 1H, H-6a00), 4.71 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10),
4.56–4.63 (m, 1H, 60-OH), 5.03–5.11 (m, 2H, OH, H-10), 5.15 (d,
0
0
4.88–4.98 (m, 1H, H-30), 5.02–5.19 (m, 3H, H-200, H-40, H-400),
1H, J = 4.5 Hz), 5.50 (d, 1H, J2 -OH,H-2 = 5.0 Hz, 20-OH), 6.06 (s, 1H,
H-3), 7.17 (dd, 1H, JH-6,H-5 = 7.6 Hz, JH-6,H-7 = 7.6 Hz, H-6), 7.30 (d,
1H, JH-8,H-7 = 8.0 Hz, H-8), 7.52 (dd, 1H, JH-7,H-6 = 7.6 Hz, JH-7,H-8
0
0
5.21–5.33 (m, 2H, H-20, H-300), 6.18 (d, 1H, JH-1 ,H-2 = 8.1 Hz, H-
100), 7.27–7.55 (m, 7H, H-5, H-7, Ph), 7.70 (d, 1H, JH-8,H-7 = 9.0 Hz,
00
00

R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
777
= 8.0 Hz, H-7), 7.93 (d, 1H, JH-5,H-6 = 7.6 Hz, H-5), 11.42 (br s, 1H,
3.6.19. 3-Ethyl-7-methoxy-4-(b-D-glucopyranosyloxy)quinolin-
NH). Anal. Calcd for C15H17NO7: C, 55.73; H, 5.30; N, 4.33. Found:
C, 55.72; H, 5.31; N, 4.26; MS (ESI+) m/z (%): 346.1 ([M+Na]+, 70),
324.1 ([M+H]+, 15), 162.1 (100); HRMS (ESI+) calcd for
C15H18NO7 ([M+H]+): 324.1083. Found: 324.1070.
2(1H)-one (5e)
White solid, mp 175–179 °C (EtOH); ½a D20
ꢃ
+4 (c 1.0, MeOH);
Rf = 0.07 (10% EtOH in CHCl3). IR (KBr) 3420 (br), 2926, 1637, 1569,
1511, 1458, 1404, 1255, 1220, 1172, 1157, 1101, 1070, 1026, 994,
668 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 1.06 (t, 3H, J = 7.4 Hz,
.
0
0
3.6.16. 3-Ethyl-4-(b-
D
-glucopyranosyloxy)quinolin-2(1H)-one
CH3CH2), 2.56–2.75 (m, 2H, CH3CH2), 3.06 (ddd, 1H, JH-5 ,H-6a =
2.1 Hz, JH-5 ,H-6b = 5.5 Hz, JH-5 ,H-4 = 8.9 Hz, H-50), 3.18 (ddd, 1H,
0
0
0
0
(5b)
White solid, mp 158–160 °C (EtOH); ½a D20
ꢃ
+12 (c 1.0, MeOH);
JH-4 ,4 -OH = 5.0 Hz, JH-4 ,H-3 = 8.6 Hz, JH-4 ,H-5 = 8.9 Hz, H-40), 3.25
0
0
0
0
0
0
0
0
0
0
0
0
Rf = 0.09 (10% EtOH in CHCl3). IR (KBr) 3403 (br), 2932, 2884,
(ddd, 1H, JH-3 ,3 -OH = 4.7 Hz, JH-3 ,H-4 = 8.6 Hz, JH-3 ,H-2 = 8.6 Hz, H-
1648, 1610, 1563, 1500, 1421, 1378, 1319, 1153, 1102, 1073,
30), 3.35–3.43 (m, 1H, H-20), 3.42–3.50 (m, 1H, H-6b0), 3.63 (ddd,
760, 678 cmꢄ1
.
1H NMR (300 MHz, DMSO-d6) d 1.09 (t, 3H,
1H, JH-6a ,H-5 = 2.1 Hz, JH-6b ,6 -OH = 5.0 Hz, JH-6b ,H-6 = 11.6 Hz, H-
0
0
0
0
0
a0
6b0), 3.80 (s, 3H, CH3O), 4.31 (dd, 1H, J6 -OH,H-6b = 5.0 Hz, J6 -OH,H-6b
0
0
0
0
J = 7.3 Hz, CH3), 2.58–2.82 (m, 2H, CH2CH3), 3.02–3.14 (m, 1H,
H-50), 3.14–3.33 (m, 2H, H-30, H-40), 3.36–3.50 (m, 2H, H-20, H-
= 5.2 Hz, 60-OH), 4.71 (d, 1H, JH-1 ,H-2 = 7.7 Hz, H-10), 4.95 (d, 1H,
0
0
a0), 3.64 (m, 1H, H-6b0), 4.33 (dd, 1H, J6 -OH,H-6b = 5.3 Hz,
J4 -OH,H-4 = 5.0 Hz, 40-OH), 5.10 (d, 1H, J3 -OH,H-3 = 4.7 Hz, 30-OH),
0
0
0
0
0
0
6
J6 -OH,H-6b = 5.3 Hz, 60-OH), 4.77 (d, 1H, JH-1 ,H-2 = 7.7 Hz, H-10),
5.76 (d, 1H, J2 -OH,H-2 = 5.1 Hz, 20-OH), 6.77 (dd, 1H, JH-6,H-5 = 8.8 Hz,
JH-6,H-8 = 2.4 Hz, H-6), 6.81 (d, 1H, JH-8,H-6 = 2.4 Hz, H-8), 8.11 (d, 1H,
JH-5,H-6 = 8.8 Hz, H-5), 11.51 (br s, 1H, NH); MS (ESI+) m/z (%):
404.1 ([M+Na]+, 14), 382.1 ([M+H]+, 14), 220.1 (100), 110.0
(18); MS ((ESIꢄ) m/z (%): 380.1 ([MꢄH]–, 36), 218.1 (100);
0
0
0
0
0
0
4.97 (d, 1H, J4 -OH,H-4 = 5.0 Hz, 40-OH), 5.13 (d, 1H, J3 -OH,H-3
=
0
0
0
0
4.7 Hz, 30-OH), 5.79 (d, 1H, J2 -OH,H-2 = 5.2 Hz, 20-OH), 7.16 (dd,
1H, JH-6,H-5 = 7.7 Hz, JH-6,H-7 = 7.6 Hz, H-6), 7.31 (d, 1H,
0
0
JH-8,H-7 = 8.0 Hz, H-8), 7.46 (dd, 1H, JH-7,H-6 = 7.6 Hz, JH-7,H-8
=
HRMS (ESI+) calcd for C18H24NO8 ([M+H]+): 382.1502. Found:
þ
8.0 Hz, H-7), 8.21 (d, 1H, JH-5,H-6 = 7.7 Hz, H-5), 11.66 (br s, 1H,
NH); MS (ESI+) m/z (%): 374.1 ([M+Na]+, 70), 352.1 ([M+H]+,
100), 324.1 (70); HRMS (ESI+) calcd for C17H22NO7 ([M+H]+):
352.1396. Found: 352.1381.
382.1510.
3.6.20. 3-Ethyl-8-methoxy-4-(b-
2(1H)-one (5f)
D-glucopyranosyloxy)quinolin-
3.6.17. 3-Phenyl-4-(b-D-glucopyranosyloxy)quinolin-2(1H)-one
White solid, mp 179–182 °C (EtOH); ½a D20
ꢄ8 (c 1.0, MeOH);
ꢃ
(5c)
White solid, mp 258–265 °C (MeOH); ½a D20
ꢄ22 (c 1.0, MeOH);
ꢃ
Rf = 0.62 (30% EtOAc in CHCl3). IR (KBr) 3412 (br), 2936, 1656,
1636, 1610, 1493, 1450, 1381, 1300, 1273, 1220, 1157, 1068,
Rf = 0.10 (9% MeOH in CH2Cl2). IR (KBr) 3408 (br), 2922, 1758,
1033, 897, 764, 735 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 1.10
.
1639, 1610, 1594, 1496, 1422, 1355, 1287, 1073, 991, 861, 764,
(t, 3H, J = 7.3 Hz, CH3C), 2.59–2.81 (m, 2H, CH2CH3), 3.07 (ddd,
702 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 2.43–2.56 (m, 1H, H-
.
1H, JH-5 ,H-6a = 1.9 Hz, JH-5 ,H-6b = 5.5 Hz, JH-5 ,H-4 = 9.2 Hz, H-50),
0
0
0
0
0
0
50), 2.82–2.91 (m, 1H, H-30), 2.95–3.05 (m, 1H, H-40), 3.12–3.20
0
0
0
0
0
0
3.18 (ddd, 1H, JH-4 ,4 -OH = 5.0 Hz, JH-4 ,H-3 = 8.2 Hz, JH-4 ,H-5
=
(m, 1H, H-20), 3.24–3.55 (m, 2H, H-6b0, H-6a0), 4.21 (br dd, 1H,
9.2 Hz, H-40), 3.27 (ddd, 1H, JH-3 ,3 -OH = 4.6 Hz, JH-3 ,H-4 = 8.2 Hz,
0
0
0
0
J6 -OH,H-6b = 5.3 Hz, J6 -OH,H-6b = 5.3 Hz, 60-OH), 4.34 (d, 1H, JH-1 ,H-2
0
0
0
0
0
0
JH-3 ,H-2 = 8.9 Hz, H-30), 3.40 (ddd, 1H, JH-2 ,2 -OH = 5.2 Hz, JH-2 ,H-1
=
0
0
0
0
0
0
= 7.7 Hz, H-10), 4.85 (br d, 1H, J4 -OH,H-4 = 5.4 Hz, 40-OH), 4.96 (br
0
0
7.8 Hz, JH-2 ,H-3 = 8.9 Hz, H-20), 3.45 (ddd, 1H, JH-6b ,6 -OH = 5.5 Hz,
0
0
0
0
d, 1H, J3 -OH,H-3 = 4.9 Hz, 30-OH), 5.31 (d, 1H, J2 -OH,H-2 = 5.0 Hz, 20-
OH), 7.20 (dd, 1H, JH-6,H-7 = 7.6 Hz, JH-6,H-5 = 7.7 Hz, H-6), 7.33 (d,
1H, JH-8,H-7 = 7.8 Hz, H-8), 7.34–7.43 (m, 5H, Ph), 7.53 (dd, 1H,
JH-7,H-6 = 7.6 Hz, JH-7,H-8 = 7.8 Hz, H-7), 8.05 (d, 1H, JH-5,H-6 = 7.7 Hz,
H-5), 11.72 (br s, 1H, NH); MS (ESIꢄ) m/z (%): 398.1 ([MꢄH]ꢄ,
0
0
0
0
JH-6b ,H-5 = 5.5 Hz, JH-6b ,6 -6b = 11.2 Hz, H-6b0), 3.64 (ddd, 1H,
0
0
0
0
0
JH-6a ,H-5 = 1.9 Hz, JH-6b ,6 -OH = 5.2 Hz, JH-6b ,H-6 = 11.2 Hz, H-6b0),
0
0
0
0
0
a0
0
0
0
0
3.90 (s, 3H, CH3O), 4.32 (dd, 1H, J6 -OH,H-6b = 5.2 Hz, J6 -OH,H-6b
=
5.5 Hz, 60-OH), 4.78 (d, 1H, JH-1 ,H-2 = 7.8 Hz, H-10), 4.97 (d, 1H,
0
0
J4 -OH,H-4 = 5.0 Hz, 40-OH), 5.13 (d, 1H, J3 -OH,H-3 = 4.6 Hz, 30-OH),
0
0
0
0
76), 236.1 (100); HRMS ((ESIꢄ) calcd for C21H20NO7 ([MꢄH]ꢄ):
ꢄ
5.78 (d, 1H, J2 -OH,H-2 = 5.2 Hz, 20-OH), 7.08–7.16 (m, 2H, H-6,
H-7), 7.78–7.85 (m, 1H, H-5), 10.63 (br s, 1H, NH). Anal. Calcd
for C18H23NO8: C, 56.69; H, 6.08; N, 3.67. Found: C, 56.80;
H, 6.27; N, 3.61; MS (ESI+) m/z (%): 382.2 ([M+H]+, 10),
220.1 (100), 214.1 (31), 158.0 (24), 104.0 (34); HRMS (ESI+)
0
0
398.1240. Found: 398.1250.
3.6.18. 3-Ethyl-6-methoxy-4-(b-
D-glucopyranosyloxy)quinolin-
2(1H)-one (5d)
White solid, mp 200–202 °C (EtOH); ½a D20
ꢃ
+13 (c 1.0, MeOH);
calcd for C18H24NO8 ([M+H]+): 382.1502. Found: 382.1510.
þ
Rf = 0.08 (10% EtOH in CHCl3). IR (KBr) 3615, 3368 (br), 2929,
1656, 1611, 1504, 1415, 1365, 1277, 1230, 1174, 1069, 1053,
1035, 831, 622 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 1.07 (t, 3H,
.
3.6.21. 3-Phenyl-6-methoxy-4-(b-D-
J = 7.3 Hz, CH3C), 2.57–2.82 (m, 2H, CH2CH3), 3.09 (ddd, 1H,
glucopyranosyloxy)quinolin-2(1H)-one (5g)
White solid, mp 175–182 °C (MeOH); ½a D20
ꢃ
0 (c 1.0, MeOH);
JH-5 ,H-6a = 2.0 Hz, JH-5 ,H-6b = 5.5 Hz, JH-5 ,H-4 = 8.9 Hz, H-50), 3.20
0
0
0
0
0
0
0
0
0
0
0
0
(ddd, 1H, JH-4 ,4 -OH = 5.0 Hz, JH-4 ,H-3 = 8.5 Hz, JH-4 ,H-5 = 8.9 Hz, H-
Rf = 0.08 (9% MeOH in CH2Cl2). IR (KBr) 3293 (br), 2936, 1643,
40), 3.27 (ddd, 1H, JH-3 ,3 -OH = 4.6 Hz, JH-3 ,H-4 = 8.5 Hz, JH-3 ,H-2
=
0
0
0
0
0
0
1618, 1597, 1506, 1445, 1411, 1350, 1282, 1226, 1182, 1088,
8.5 Hz, H-30), 3.42 (ddd, 1H, JH-2 ,2 -OH = 4.9 Hz, JH-2 ,H-1 = 7.9 Hz,
1022, 824, 704 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 2.54–2.62
.
0
0
0
0
JH-2 ,H-3 = 8.5 Hz, H-20), 3.46 (ddd, 1H, JH-6b ,6 -OH = 5.4 Hz, JH-6b ,H-5
(m, 1H, H-50), 2.85–3.04 (m, 2H, H-30, H-40), 3.10–3.20 (m, 1H,
0
0
0
0
0
0
= 5.5 Hz, JH-6b ,6 -6b = 11.5 Hz, H-6b0), 3.64 (ddd, 1H, JH-6a ,H-5
=
H-20), 3.22–3.45 (m, 1H, H-6a0), 3.44–3.56 (m, 1H, H-6a0), 3.80
0
0
0
0
0
2.0 Hz, JH-6b ,6 -OH = 4.0 Hz, JH-6b ,H-6 = 11.5 Hz, H-6b0), 3.77 (s, 3H,
(s, 3H, CH3O), 4.06–4.12 (m, 1H, 60-OH), 4.40 (d, 1H, JH-1 ,H-2
0
0
0
a0
0
0
CH3O), 4.33 (dd, 1H, J6 -OH,H-6b = 5.0 Hz, J6 -OH,H-6b = 5.4 Hz, 60-OH),
= 7.7 Hz, H-10), 4.85 (d, 1H, J4 -OH,H-4 = 5.2 Hz, 40-OH), 4.97 (d,
0
0
0
0
0
0
4.76 (d, 1H, JH-1 ,H-2 = 7.9 Hz, H-10), 4.95 (d, 1H, J4 -OH,H-4 = 5.0 Hz,
1H, J3 -OH,H-3 = 4.7 Hz, 30-OH), 5.43 (d, 1H, J2 -OH,H-2 = 4.9 Hz, 20-
OH), 7.18 (dd, 1H, JH-7,H-8 = 8.9 Hz, JH-7,H-5 = 2.7 Hz, H-7), 7.27 (d,
1H, JH-8,H-7 = 8.9 Hz, H-8), 7.31–7.39 (m, 5H, Ph), 7.62 (d, 1H,
JH-5,H-7 = 2.7 Hz, H-5), 11.67 (br s, 1H, NH); MS (ESI+) m/z (%):
452.1 ([M+Na]+, 99), 430.1 ([M+H]+, 35), 268.1 (100), 236.1
0
0
0
0
0
0
0
0
40-OH), 5.13 (d, 1H, J3 -OH,H-3 = 4.6 Hz, 30-OH), 5.90 (d, 1H, J2 -OH,H-2
= 4.9 Hz, 20-OH), 7.09 (dd, 1H, JH-7,H-8 = 8.9 Hz, JH-7,H-5 = 2.8 Hz,
H-7), 7.23 (d, 1H, JH-8,H-7 = 8.9 Hz, H-8), 7.86 (d, 1H, JH-5,H-7
= 2.8 Hz, H-5), 11.56 (br s, 1H, NH); MS (ESI+) m/z (%): 382.2
0
0
0
0
([M+H]+, 16), 220 (100); HRMS (ESI+) calcd for C18H24NO8
þ
(88); HRMS (ESI+) calcd for C22H24NO8 ([M+H]+): 430.1502.
þ
([M+H]+): 382.1502. Found: 382.1509.
Found: 430.1486.

778
R. Kimmel et al. / Carbohydrate Research 345 (2010) 768–779
53, 2545–2551; (c) Shibata, H.; Nanbu, T.; Tateishi, K.; Shimizu, S. Agric. Biol.
3.6.22. 3-Phenyl-7-methoxy-4-(b-
quinolin-2(1H)-one (5h)
D-glucopyranosyloxy)-
Chem. 1989, 53, 849–850.
3. Su, Y.-F.; Luo, Y.; Guo, C.-Y.; Guo, D.-A. J. Asian Nat. Prod. Res. 2004, 6, 223–227.
4. Michael, J. P. Nat. Prod. Rep. 2007, 24, 223–246.
5. Dembitsky, V. M. Lipids 2005, 40, 1081–1105.
White solid, mp 272–285 °C (MeOH–EtOAc); ½a D20
ꢄ35 (c 1.0,
ꢃ
MeOH); Rf = 0.09 (9% MeOH in CH2Cl2). IR (KBr) 3406 (br), 2925,
6. Rasulova, K. A.; Bessonova, I. A.; Yagudaev, M. R.; Yunusov, S. Y. Khim. Prirod.
Soed. 1987, 6, 876–879.
1637, 1554, 1509, 1443, 1353, 1281, 1259, 1208, 1170, 1070,
1030, 863, 703 cmꢄ1 1H NMR (300 MHz, DMSO-d6) d 2.50 (ddd,
.
7. Akhmedzhanova, V. I.; Rasulova, K. A.; Bessonova, I. A.; Shashkov, A. S.;
Abdullaev, N. D.; Angenot, L. Chem. Nat. Compd. 2005, 41, 60–64.
8. (a) Smith, J. N. Biochem. J. 1953, 55, 156–160; (b) Smith, J. N.; Williams, R. T.
Biochem. J. 1954, 56, 325–329; (c) Smith, J. N.; Williams, R. T. Biochem. J. 1955,
60, 284–290.
1H, JH-5 ,H-6b = 1.0 Hz, JH-5 ,H-6a = 5.1 Hz, JH-5 ,H-4 = 9.3 Hz, H-50),
0
0
0
0
0
0
0
0
0
0
0
0
2.86 (ddd, 1H, JH-3 ,3 -OH = 5.0 Hz, JH-3 ,H-2 = 8.9 Hz, JH-3 ,H-4
=
9.0 Hz, H-30), 2.99 (ddd, 1H, JH-4 ,4 -OH = 5.4 Hz, JH-4 ,H-3 = 9.0 Hz,
0
0
0
0
JH-4 ,H-5 = 9.3 Hz, H-40), 3.13 (ddd, 1H, JH-2 ,2 -OH = 5.0 Hz, JH-2 ,H-1
=
0
0
0
0
0
0
9. Baglioni, C.; Fasella, P.; Turano, C.; Siliprandi, N. Biochem. J. 1960, 74,
521–525.
7.8 Hz, JH-2 ,H-3 = 8.9 Hz, H-20), 3.27 (dd, 1H, JH-6b ,6 OH = 5.2 Hz,
0
0
0
0
10. Burka, L. T.; Sanders, J. M.; Matthews, H. B. Xenobiotica 1996, 26, 597–611.
11. (a) Ferre, J.; Real, M. D.; Mensua, J. L.; Jacobson, K. B. J. Biol. Chem. 1985, 260,
7509–7514; (b) Real, M. D.; Ferre, J. J. Biol. Chem. 1990, 265, 7407–7412.
12. (a) Shirao, E.; Ando, K.; Inoue, A.; Shirao, Y.; Balasubramanian, D. Exp. Eye Res.
2001, 73, 421–431; (b) Thiagarajan, G.; Shirao, E.; Ando, K.; Inoue, A.;
Balasubramanian, D. Photochem. Photobiol. 2002, 76, 368–372.
13. Cain, C. D.; Schroeder, F. C.; Shankel, S. W.; Mitchnick, M.; Schmertzler, M.;
Bricker, N. S. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 17873–17878.
14. Suzuki, H.; Nagasawa, H.; Igarashi, I.; Igarashi, M.; Tanaka, I.; Suzuki,
N. Jpn. Kokai Tokkyo Koho JP 2006056872, 2006; Chem. Abstr. 2006, 144,
205733.
JH-6b ,H-5 = 1.0 Hz, JH-6b ,H-6a = 11.6 Hz, H-6a0), 3.49 (ddd, 1H,
0
0
0
0
JH-6a ,6 OH = 5.2 Hz, JH-6a ,H-5 = 5.1 Hz, JH-6a ,H-6b = 11.6 Hz, H-6a0),
0
0
0
0
0
0
0
0
0
0
3.82 (s, 3H, CH3O), 4.18 (dd, 1H, J6 -OH,H-6b = 5.2 Hz, J6 -OH,H-6a
=
5.2 Hz, 60-OH), 4.32 (d, 1H, JH-1 ,H-2 = 7.8 Hz, H-10), 4.83 (d, 1H,
0
0
J4 -OH,H-4 = 5.4 Hz, 40-OH), 4.94 (d, 1H, J3 -OH,H-3 = 5.0 Hz, 30-OH),
0
0
0
0
5.27 (d, 1H, J2 -OH,H-2 = 5.0 Hz, 20-OH), 6.79–6.84 (m, 2H, H-6,
H-8), 7.27–7.39 (m, 5H, Ph), 7.94 (d, 1H, JH-5,H-6 = 9.6 Hz, H-5),
11.62 (br s, 1H, NH); MS (ESI+) m/z (%): 452.1 ([M+Na]+, 68),
430.2 ([M+H]+, 10), 268.1 (24), 236.1 (100); HRMS (ESI+) calcd
0
0
15. Suzuki, H.; Aly, N. S. M.; Wataya, Y.; Kim, H.-S.; Tamai, I.; Kita, M.; Uemura, D.
Chem. Pharm. Bull. 2007, 55, 821–824.
16. Nógrádi, T.; Vargha, L.; Ivánovics, G.; Koczka, I. Acta Chim. Acad. Sci. Hung. 1955,
6, 287–293.
for C22H24NO8 ([M+H]+): 430.1502. Found: 430.1500.
þ
17. Takagaki, H.; Nakanishi S.; Kimura, N.; Yamaguchi, S.; Aoki, Y. Eur. Pat. Appl. EP
933378, 1999; Chem. Abstr. 1999, 131, 116454.
18. Hirayama, B. A.; Diez-Sampedro, A.; Wright, E. M. Br. J. Pharmacol. 2001, 134,
484–495.
3.6.23. 3-Phenyl-8-methoxy-4-(b-
quinolin-2(1H)-one (5i)
D-glucopyranosyloxy)-
White solid, mp 142–145 °C (EtOAc); ½a D20
ꢄ28 (c 1.0, MeOH);
ꢃ
Rf = 0.63 (30% EtOAc in CHCl3). IR (KBr) 3389 (br), 2922, 1638,
19. For selected recent review articles on glycosylations, see: (a) Toshima, K.;
Tatsuta, K. Chem. Rev. (Washington, DC, U.S.) 1993, 93, 1503–1531; (b)
Hanessian, S.; Lou, B. Chem. Rev. (Washington, DC, U.S.) 2000, 100, 4443–
4463; (c) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed. 2001, 40, 1576–
1624; (d) Demchenko, A. V. Synlett 2003, 1225–1240; (e) Toshima, K.
Carbohydr. Res. 2006, 341, 1282–1297; (f) Galonic, D. P.; Gin, D. Y. Nature
(London, U.K.) 2007, 446, 1000–1007; (g) Zhu, X.; Schmidt, R. R. Angew. Chem.,
Int. Ed. 2009, 48, 1900–1934.
20. (a) Wagner, G.; Schmidt, R. Z. Chem. 1964, 4, 145–146; (b) Wagner, G.; Schmidt,
R. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1965, 298, 481–491; (c) Wagner, G.;
Schmidt, R. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1965, 298, 466–475; (d)
Wagner, G.; Schmidt, R. Arch. Pharm. Ber. Dtsch. Pharm. Ges. 1967, 300, 772–773.
21. For selective O-alkylation of quinolinones, see: Morel, A. F.; Larghi, E. L.;
Selvero, M. M. Synlett 2005, 2755–2758. and references therein.
22. (a) Kafka, S.; Košmrlj, J.; Klásek, A.; Pevec, A. Tetrahedron Lett. 2008, 49, 90–93;
(b) Košmrlj, J.; Kafka, S.; Leban, I.; Grad, M. Magn. Reson. Chem. 2007, 45, 700–
1612, 1500, 1352, 1305, 1275, 1260, 1161, 1070, 1040, 883, 779,
702 cmꢄ1
.
1H NMR (300 MHz, DMSO-d6) d 2.50 (ddd, JH-5 ,H-6b
0
0
= 1.9 Hz, JH-5 ,H-6b = 5.6 Hz, JH-5 ,H-4 = 8.9 Hz, 1H, H-50), 2.84
0
0
0
0
0
0
0
0
0
0
(ddd, 1H, JH-3 ,3 -OH = 5.0 Hz, JH-3 ,H-4 = 8.9 Hz, JH-3 ,H-2 = 8.8 Hz, H-
30), 2.97 (ddd, 1H, JH-4 ,4 -OH = 5.5 Hz, JH-4 ,H-3 = 8.9 Hz, JH-4 ,H-5
=
0
0
0
0
0
0
8.9 Hz, H-40), 3.13 (ddd, 1H, JH-2 ,2 -OH = 5.0 Hz, JH-2 ,H-1 = 7.7 Hz,
0
0
0
0
JH-2 ,H-3 = 8.8 Hz, H-20), 3.28 (ddd, 1H, JH-6b ,6 -OH = 5.3 Hz, JH-6b ,H-5
0
0
0
0
0
0
= 5.6 Hz, JH-6b ,H-6a = 11.6 Hz, H-6a0), 3.50 (ddd, 1H, JH-6b ,H-5
=
0
0
0
0
1.9 Hz, JH-6b ,H-6 = 11.6 Hz, JH-6b ,6 -OH = 5.3 Hz, H-6b0), 3.91 (s, 3H,
a0
0
0
0
CH3O), 4.20 (dd, 1H, J6 -OH,H-6 = 5.3 Hz, J6 -OH,H-6a = 5.3 Hz, 60-OH),
0
0
0
a0
4.31 (d, 1H, JH-1 ,H-2 = 7.7 Hz, H-10), 4.83 (d, 1H, J4 -OH,H-4 = 5.5 Hz,
0
0
0
0
40-OH), 4.94 (d, 1H, J3 -OH,H-3 = 5.0 Hz, 30-OH), 5.30 (d, 1H, J2 -OH,H-2
0
0
0
0
ˇ
704; (c) Klásek, A.; Mrkvicka, V.; Pevec, A.; Košmrlj, J. J. Org. Chem. 2004, 69,
= 5.0 Hz, 20-OH), 7.11–7.21 (m, 2H, H-6, H-7), 7.63 (dd, 1H,
JH-5,H-7 = 2.4 Hz, JH-5,H-6 = 7.0 Hz, H-5), 10.74 (br s, 1H, NH); MS
(ESI+) m/z (%): 430.2 ([M+H]+, 18), 268.1 (100); HRMS (ESI+) calcd
ˇ
5646–5651; (d) Klásek, A.; Koristek, K.; Kafka, S.; Košmrlj, J. Heterocycles 2003,
ˇ
60, 1811–1820; (e) Klásek, A.; Polis, J.; Mrkvicka, V.; Košmrlj, J. J. Heterocycl.
Chem. 2002, 39, 1315–1320; (f) Kafka, S.; Klásek, A.; Polis, J.; Košmrlj, J.
Heterocycles 2002, 57, 1659–1682; (g) Kafka, S.; Klásek, A.; Košmrlj, J. J. Org.
Chem. 2001, 66, 6394–6399.
for C22H24NO8 ([M+H]+): 430.1502. Found: 430.1515.
þ
23. (a) Baumgarten, P.; Kärgel, W. Ber. Dtsch. Chem. Ges. 1927, 60, 832–842; (b)
Cooke, R. G.; Haynes, H. F. Aust. J. Chem. 1954, 7, 273–276; (c) Rapoport, H.;
Holden, K. G. J. Am. Chem. Soc. 1959, 81, 3738–3743; (d) Stadlbauer, W.;
Schmut, O.; Kappe, T. Monatsh. Chem. 1980, 111, 1005–1013; (e) Stadlbauer,
W.; Kappe, T. Monatsh. Chem. 1985, 116, 1005–1015.
Acknowledgements
This study was supported by the Czech Science Foundation
(Grant No. 203/07/0320), by the Ministry of Education, Youth and
Sports of the Czech Republic (Project MSM7088352101 and Joint
Project Nr 9-06-3 of Programme KONTAKT), Tomas Bata Founda-
tion and the Slovenian Research Agency (Project P1-0230-0103
24. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.;
Wiley: New York, 1999.
25. For selected examples, see: (a) Baston, E.; Palusczak, A.; Hartmann, R. W. Eur. J.
Med. Chem. 2000, 35, 931–940; (b) Teramoto, S.; Tanaka, M.; Shimizu, H.;
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Tominaga, M. J. Med. Chem. 2003, 46, 3033–3044; (c) Grosch, B.; Orlebar, C. N.;
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26. Cai, T. B.; Lu, D.; Tang, X.; Zhang, Y.; Landerholm, M.; Wang, P. G. J. Org. Chem.
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and Joint Project BI-CZ/07-08-018). The authors thank Dr. Bogdan
ˇ
ˇ
Kralj and Dr. Dušan Zigon (Mass Spectrometry Center, Jozef Stefan
Institute, Ljubljana, Slovenia) for mass spectral measurements and
the reviewers of this manuscript for valuable suggestions.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.01.023.
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