Synthesis of quinoline-based glycoconjugates: A facile one-pot three-component reaction

Article abstract of DOI:10.1016/j.carres.2011.02.008

A multicomponent one-pot reaction involving propargyl glycosides, methoxy-substituted aromatic aldehydes and aromatic amines using Cu(I) as catalyst is described, which provides an efficient and practical route to synthesize several quinoline-based glycoc

Full text of DOI:10.1016/j.carres.2011.02.008

Carbohydrate Research 346 (2011) 728–732
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of quinoline-based glycoconjugates: a facile one-pot
three-component reaction
⇑
K. Karthik Kumar, Thangamuthu Mohan Das
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A multicomponent one-pot reaction involving propargyl glycosides, methoxy-substituted aromatic alde-
hydes and aromatic amines using Cu(I) as catalyst is described, which provides an efficient and practical
route to synthesize several quinoline-based glycoconjugates in good yield.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 16 December 2010
Received in revised form 2 February 2011
Accepted 7 February 2011
Available online 12 February 2011
Keywords:
Glycoconjugates
Quinoline derivatives
Multi-component
Propargyl glycosides
Cu(I) catalyst
1. Introduction
eral natural products and libraries of compounds for the discovery
of biological probes and drugs.10 Therefore, MCR is more ideal for
The design and synthesis of novel molecular scaffolds with un-
ique structural and biological properties is an increasingly active
area of current chemical research.1 The importance of glycobiology
and subsequently the chemistry of glycoconjugates has gained
enormous attention over the past few years owing to the under-
standing of the role played by these carbohydrates in several bio-
logical events.2–5 These glycoconjugates, which mainly exist as
glycolipids or glycoproteins play a unique role in different events
such as cell adhesion, cell growth, inflammation, and immune re-
sponses.6 Moreover, several naturally occurring carbohydrates
contain a range of more or less complex glycosylated aromatic
moieties of plant origin such as arbutin (1), sennoside A (2), glucof-
rangulin (3) (Fig. 1).7 Thus, the efficient synthesis of not only sim-
ple carbohydrates, but also carbohydrate-containing complex
natural products is becoming a more important and challenging
field in current synthetic organic chemistry and chemical biology.8
Moreover, quinoline and its derivatives are also well-known
important biological components. Some of the quinoline deriva-
tives such as quinine, chloroquine, and amodiaquine are important
for the treatment of malaria. In addition, some of the synthetic
quinolines exhibit significant activities in the treatment of many
infectious diseases.9
preparing complex structures by a sequence of reactions that
assembles several components. Multicomponent reactions such
as the Hantzsch11 and Biginelli12 reactions are important for syn-
thesis of several heterocycles, while the MCRs of Passerini,13
Ugi,14 and Petasis15 are useful methods for synthesizing amino car-
boxylic acid derivatives.16 Thereby, it is desirable to devise novel
methods for easy access to heterocyclic derivatives in view of their
great potential utility in biological and pharmaceutical studies
where the development of multicomponent process would well
serve this purpose.
Recently, Doye and co-workers17 carried out a three-component
reaction using the acetylenic moiety as one of the components in
synthesizing dihydroisoquinolines. Moreover, Trofimov et al.,18,19
have also utilized acetylene with an aldehyde and imidazole to car-
ry out a three-component reaction. In addition, a one-pot four-
component reaction involving acetylene, a substituted aldehyde,
an azide, an aromatic amine, and ammonium acetate in synthesis
of phenylquinazolines was carried out by Dabiri et al.20 Similarly,
Gao and Wu21 synthesized dihydroisoquinolines using acetylene,
a substituted aldehyde, an aromatic amine, and benzyl/allyl bro-
mide in a multicomponent reaction involving Mg–Cu as a catalyst.
It has also been reported by Nevado and co-workers that cyclopro-
pyl propargylic carboxylates can be used in synthesizing alkylid-
In general, multicomponent reactions (MCRs) are an important
class of chemical transformations for the efficient synthesis of sev-
enecyclopentyl acetates using
a
gold catalyst.22 However,
Masciadri and co-workers23 have synthesized quinoline com-
pounds using 2-aminoarylketones with various b-keto derivatives.
A detailed study shows that most of the one-pot reaction involves
⇑
Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494.
E-mail address: tmdas_72@yahoo.com (T. Mohan Das).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.02.008

K. Karthik Kumar, T. Mohan Das / Carbohydrate Research 346 (2011) 728–732
729
OH
O
HO
HO
O
O
O
H
OH
OH
OH
COOH
COOH
OH
O
HO
HO
H
O
O
OH
OH
O
HO
HO
OH
OH
(1)
(2)
OH
O
HO
HO
O
O
O
OH
OH
O
CH3
H3C
HO
O
HO
OH
(3)
Figure 1. Naturally occurring glycosylated compounds (1–3).
amine, aldehyde, and acetylene moieties to synthesize quinoline
and its derivatives. In the context of our studies in the area of
MCRs, we would like to report an efficient approach for the one-
pot synthesis of quinoline-coupled saccharide molecules.
mining the preferred solvent for this reaction was attempted using
acetonitrile, DMF, ethanol, and water, all of which showed no supe-
riority over THF (Table 1, entries 12–15). In addition, we also eval-
uated the amount of CuCl used in this reaction. It was found that
when we increase the amount of CuCl catalyst from 10% to 30%,
the yield gradually increased. However, the use of 30% CuCl in
THF is sufficient enough to push the reaction forward toward the
expected quinoline-coupled saccharide compound in moderate
yield. However, an additional amount of the catalyst did not im-
prove the yields (Table 1, entries 16–18).
2. Results and discussion
As a part of our ongoing project devoted toward the develop-
ment of interesting heterocyclic-coupled saccharide molecules
with varied applications in the field of materials science and
medicinal chemistry,24,25 herein we have explored the possibility
of a one-pot multicomponent synthesis of quinoline-coupled sac-
charide molecules. In this paper we report a new three-component
reaction between an aromatic aldehyde, an aromatic amine, and
propargyl glycosides that leads to a novel class of quinoline deriv-
atives that possess a substituent at the C-2 position with a benzene
moiety and saccharide moiety at the C-4 position.
Thus, under optimized reaction conditions a series of quinoline-
based glycoconjugates (7a–f) were synthesized as shown in
Scheme 1. In order to evaluate the formation of the expected quin-
oline-based glycoconjugates, the reaction was carried with propar-
gyl glycosides of D-glucose and D
-galactose.26 A detailed study was
performed on the reactivity of different substrates and also on the
selectivity of the reaction toward the formation of quinoline-based
glycoconjugates. However, formation of propargyl amine varied
depending on the aromatic aldehyde/amine used in the course of
the reaction. It is therefore important to reveal the selectivity of
aromatic aldehydes and amines in this reaction to obtain the ex-
pected quinoline-based glycoconjugate as the product. It is inter-
esting to note that the use of alkyl, halogen or unsubstituted
aromatic aldehyde and aromatic amine with propargyl glycoside
results in a propargyl amine as the major product. A similar obser-
vation has been reported in the literature.27 Since the formation of
propargyl amine has been studied exclusively in the literature,27
we focused on the reaction conditions and substituents favoring
the formation of the expected quinoline-based glycoconjugates.
Benzaldehyde and its derivatives 4a–b reacted with aniline 5a
Initially, to synthesize quinoline-coupled saccharide deriva-
tives, the one-pot three-component reaction was carried out using
3,4-dimethoxybenzaldehyde, aniline and propargyl tetra-O-acetyl-
b-D-galactopyranoside (6a) as a simple model substrate under var-
ious reaction conditions. The results are summarized in Table 1. It
was found that when the reaction was carried out without any cat-
alyst the expected quinoline-coupled saccharide product was not
observed, even after 24 h (Table 1, entry 1). In order to optimize
the reaction conditions we examined the reaction using different
Brønsted and Lewis acids (Table 1, entries 2–10). Brønsted acids
such as HCl and p-TSA were not able to catalyze the reaction, even
after prolonged reaction times (Table 1 entries 2 and 3). However,
the use of Lewis acid catalysts such as BF3ÁOEt2, FeCl3, Cu(OAc)2,
CuCl2, CuI, and CuBr led to low or no product formation (Table 1,
entries 4–9). Finally, CuCl was identified as the optimum catalyst,
resulting in the formation of 7c in ꢀ54% yield (Table 1, entry 10).
However, carrying out the reaction in the presence of CuCl at room
temperature resulted in <5% yield of 7c even after prolonged reac-
tion time (Table 1, entry 11). Subsequently, optimization by deter-
and the propargyl glycoside of D-galactose 6a to yield quinoline-cou-
pled saccharide compound 7a–b in 34–35% yield. As suggested, the
propargyl amine was observed in a higher ratio than the expected
quinoline glycoconjugates (7a–b). Moreover, 3,4-dimethoxybenzal-
dehyde (4d) with aniline (5a) and the propargyl glycoside of
D-gal-
actose (6a), results in satisfactory to good yield of compound 7c

730
K. Karthik Kumar, T. Mohan Das / Carbohydrate Research 346 (2011) 728–732
Table 1
Optimization of the reaction conditions for the synthesis of quinoline derivatives
AcOOAc
AcO
O
O
O
H
AcO
AcO
OAc
NH2
OAc
O
Solvent
Catalyst
CH3
O
O
OAc
N
O
CH3
CH3
O
O
CH3
Entry
Solvent
Temperature (°C)
Catalyst
Time (h)
Yield (%)
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
CH3CN
DMF
Ethanol
Water
THF
60
60
60
60
60
60
60
60
60
60
rt
80
90
80
80
60
60
60
Without catalyst
HCl (30%)
24
24
24
8
8
8
8
8
8
8
24
8
8
8
24
8
—
—
—
—
p-TSA (30%)
BF3–OEt (30%)
FeCl3 (30%)
Cu(OAc)2 (30%)
CuCl2 (30%)
CuI (30%)
CuBr (30%)
CuCl (30%)
CuCl (30%)
CuCl (30%)
CuCl (30%)
CuCl (30%)
CuCl (30%)
CuCl (10%)
CuCl (20%)
CuCl (40%)
<5
15
13
21
28
54
<5
43
35
12
—
14
28
56
THF
THF
8
8
(54%) in comparison with quinoline-based glycoconjugates 7a–b.
Therefore, the involvement of a methoxy-substituted benzaldehyde
that favors the formation of quinoline-based glycoconjugates has
been observed. Moreover, it is also important to study the effect of
methoxy substitution in aniline in favoring the formation of quino-
line-based glycoconjugates. As a result methoxy-substituted ani-
line, p-anisidine (5b) was treated with benzaldehyde (4a) in the
presence of the propargyl glycoside of D-glucose (6b) leading to
the formation of quinoline glycoconjugate 7d in a yield of 61%. These
results further proved that the methoxy-substituted aniline also fa-
vors the formation of quinoline glycoconjugates. Similarly methoxy-
substituted benzaldehydes 4c and 4d with p-anisidine (5b) in pres-
ence of propargyl glycoside (6b) were subjected to a one-pot reac-
tion involving three components to yield the expected product 7e
O
H
R4
OAc
NH2
R3
O
CuCl
THF
R1
R2
O
AcO
OAc
4a R1 = H
6a R3 = H; R4 = OAc
6b R3 = OAc; R4 = H
5a R2 = H
4b R1 = 4-Cl
5b R2 = 4-OMe
4c R1 = 4-OMe
4d R1 = 3,4-di-OMe
R4
OAc
R2
R3
O
O
AcO
OAc
N
R1
7a R1 = R2 = R3 = H; R4 = OAc
7b R1 = 4-Cl; R2 = R3 = H; R4 = OAc
7c R1 = 3, 4-OMe; R2 = R3 = H; R4 = OAc
7d R1 = H; R2 = 4-OMe; R3 = OAc; R4 = H
7e R1 = 4-OMe; R2 = 4-OMe; R3 = OAc; R4 = H
7f R1 = 3,4-di-OMe; R2 = 4-OMe; R3 = OAc; R4 = H
Scheme 1. Synthesis of quinoline-based glycoconjugates 7a–f.

K. Karthik Kumar, T. Mohan Das / Carbohydrate Research 346 (2011) 728–732
731
Table 2
Chemical shift (ppm) and coupling constant (Hz) of the anomeric proton (H-1) and anomeric carbon (Ano-C) including yield of compounds 7a–f
Entry No.
Compd No.
H-1 (ppm)
Coupling constant, J (Hz)
Ano-C (ppm)
Yield (%)
1.
2.
3.
4.
5.
6.
7a
7b
7c
7d
7e
7f
4.65 (d)
4.53 (d)
4.68 (d)
4.58 (d)
4.56 (d)
4.57 (d)
8.1
7.8
7.8
7.8
7.8
7.8
100.2
100.3
100.4
98.1
99.4
99.7
34
35
54
61
52
51
(52%) and 7f (51%), respectively. All these results show that the
methoxy-substituted benzaldehyde/aniline favors the formation of
quinoline-based glycoconjugates. In most of the cases studied with
methoxy-substituted aniline/benzaldehyde, the byproduct propar-
gylamine was observed in a very low yield (<5%). Moreover, our
observations were supported from the results of Iqbal and co-work-
ers28 with non-sugar hybrids of quinoline compounds. It is also
4.1.1. General procedure for synthesis of 4-glycosyloxymethyl-
2-phenylquinoline derivatives 7a–f
To a suspension of aniline 5a (0.24 mL, 2.68 mmol) in 5 mL of
dry THF was added benzaldehyde 4a (0.25 mL, 2.68 mmol) and
the mixture was stirred for 0.5 h. 2-Propyn-1-yl 2,3,4,6-tetra-O-
acetyl-b-D-galactopyranoside (6a, 0.84 g, 2.28 mmol) in 5 mL of
THF treated with CuCl (0.07 g, 0.68 mmol) was slowly added to
the mixture of aniline and benzaldehyde, and the mixture was
heated at 65 °C for 8 h. After completion of the reaction as moni-
tored by TLC, the mixture was filtered over a Celite bed where
the filtrate was washed with water, followed with brine, to give
the crude product, which then purified by column chromatography
on silica gel using 9:1 CHCl3–MeOH as eluant to furnish the prod-
interesting to note that variation of propargyl sugars from
ose (6a) to -glucose (6b) also favors the formation of quinoline-
based glycoconjugates.
D-galact-
D
Structural information for the expected quinoline glycoconju-
gates (7a–f) was obtained by NMR studies. Compounds 7a–f exhib-
ited the b-anomeric form (d 4.6 ppm, J 7.8 Hz) as a doublet, as
evident from 1H NMR studies (Table 2). The 13C NMR spectra of
the quinoline glycoconjugates 7a–f confirmed the presence of a
glycoconjugated product as the anomeric carbon was identified
at 98.1–100.4 ppm. The acetyl groups present in the saccharide
moiety of the quinoline glycoconjugates are well resolved in both
1H and 13C NMR spectra. The acetyl protons corresponding to the
synthesized compounds 7a–f resonate in the region of 2.11–
1.85 ppm in 1H NMR spectra, and the corresponding 13C NMR sig-
nals are observed around 20.3–20.8 ppm. The 1H NMR spectra of
the quinoline glycoconjugates exhibit signals for the aromatic ring
of the quinoline core structure in the region of 8.22–6.98 ppm.
However, the aromatic carbons in the 13C NMR spectrum corre-
sponding to the quinoline core structure resonate in the region of
158.1–110.2 ppm, which provides evidence for the quinoline over
the possible propargyl amine. All these observations provide a
clear support for the formation the 2,4-disubstituted quinolines
coupled to the saccharide moiety.
uct,
2-phenyl-4-((2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl-
oxy)methyl)quinoline (7a) as an oily liquid (0.43 g, 34%): 1H NMR
(300 MHz, CDCl3): dH 7.61–8.22 (m, 5H, Qui-H), 7.47–7.58 (m,
5H, Qui-H), 4.94–5.48 (m, 4H, Sacc-H), 4.65 (d, 1H, J = 8.1 Hz, H-
1), 4.58 (s, 2H, CH2), 3.93–4.55 (m, 2H, Sacc-H), 1.83–2.18 (m,
12H, Ace-H). dC 169.4–170.4 (4C, Ace-C@O), 114.2–157.1 (15C,
Qui-C), 100.2 (1C, Ano-C), 61.3–70.9 (6C, Sacc-C), 20.6–20.7 (4C,
Ace-CH3). Anal. Calcd for C30H31NO10 (565.19): C, 63.71; H, 5.52;
N, 2.48. Found: C, 63.52; H, 5.35; N, 2.21.
4.1.2. 2-(4-Chlorophenyl)-4-((2,3,4,6-tetra-O-acetyl-b-D-
galactopyranosyloxy)methyl)quinoline (7b)
A mixture of p-chlorobenzaldehyde (4b, 0.32 mL, 2.68 mmol),
aniline (5a, 0.24 mL, 2.68 mmol), 2-propyn-1-yl-2,3,4,6-tetra-O-
acetyl-b-D-galactopyranoside (6a, 0.84 g, 2.28 mmol) and CuCl
(0.07 g, 0.68 mmol) in 10 mL of THF afforded compound 7b as an
oily liquid (0.48 g, 35%); 1H NMR (300 MHz, CDCl3): dH 7.88–8.20
(m, 5H, Qui-H), 7.49–7.77 (m, 4H, Qui-H), 4.66–5.50 (m, 4H,
Sacc-H), 4.53 (d, 1H, J = 7.8 Hz, H-1), 4.45 (s, 2H, CH2), 3.88–4.38
(m, 2H, Sacc-H), 1.99–2.11 (m, 12H, Ace-H). dC 169.5–170.5 (4C,
Ace-C@O), 130.6–157.3 (5C, Qui-C), 114.3–129.7 (10C, Qui-C),
100.3 (1C, Ano-C), 50.1–71.1 (6C, Sacc-C), 20.6–20.8 (4C, Ace-
CH3). Anal. Calcd for C30H30ClNO10 (599.16): C, 60.05; H, 5.04; N,
2.33. Found: C, 60.42; H, 5.23; N, 2.56.
3. Conclusions
In conclusion, we have reported the synthesis of a novel class of
quinoline-based glycoconjugates. The most noteworthy aspect of
this research is the development of an efficient and general route
for the synthesis of the quinoline-based glycoconjugates through
a one-pot synthesis from an aryl amine, an aryl aldehyde and a
propargyl glycoside. This methodology of a one-pot three compo-
nent reaction in the synthesis of quinoline with substitution at
the C-2 and C-4 positions appears attractive for the combinatorial
synthesis of a quinoline glycoconjugate library.
4.1.3. 2-(3,4-Dimethoxyphenyl)-4-((2,3,4,6-tetra-O-acetyl-b-D-
galactopyranosyloxy)methyl)quinoline (7c)
A
mixture of 3,4-dimethoxybenzaldehyde (4d, 0.44 g,
2.68 mmol), aniline (5a, 0.24 mL, 2.68 mmol), 2-propyn-1-yl-
2,3,4,6-tetra-O-acetyl-b- -galactopyranoside (6a, 0.84 g,
D
2.28 mmol) and CuCl (0.07 g, 0.68 mmol) in 10 mL of THF afforded
compound 7c as an oily liquid (0.77 g, 54%); 1H NMR (300 MHz,
CDCl3): dH 7.85–8.20 (m, 4H, Qui-H), 7.01–7.79 (m, 4H, Qui-H),
5.36–5.51 (m, 5H, Sacc-H), 4.68 (d, 1H, J = 7.8 Hz, H-1), 4.55 (s,
2H, CH2), 4.10–4.52 (m, 1H, Sacc-H), 3.98 (s, 3H, Qui-OCH3), 3.97
(s, 3H, Qui-OCH3), 1.85–2.18 (m, 12H, Ace-H). dC 169.5–170.4 (4C,
Ace-C@O), 142.2–156.6 (5C, Qui-C), 110.3–132.2 (10C, Qui-C),
100.4 (1C, Ano-C), 61.2–70.8 (6C, Sacc-C), 56.1 (1C, Qui-OCH3),
55.9 (1C, Qui-OCH3), 20.6–20.7 (4C, Ace-CH3). Anal. Calcd for
C32H35NO12 (625.22): C, 61.43; H, 5.64; N, 2.24. Found: C, 61.36;
H, 5.69; N, 2.63.
4. Experimental
4.1. General methods
1H and 13C NMR spectra were measured on a Bruker Avance 300
NMR spectrometer using tetramethylsilane (Me4Si) as the internal
standard. Elemental analyses were carried out using an Eager 300
C,H,N analyser at IIT Bombay (Mumbai, India). Thin-layer chroma-
tography (TLC) was performed on manually coated plates (Acme)
with detection by UV light or iodine vapour. Column chromatogra-
phy was performed using SiO2 (Acme 100–200 mesh).

732
K. Karthik Kumar, T. Mohan Das / Carbohydrate Research 346 (2011) 728–732
4.1.4. 6-Methoxy-2-phenyl-4-((2,3,4,6-tetra-O-acetyl-b-
glucopyranosyloxy)methyl)quinoline (7d)
A mixture of benzaldehyde (4a, 0.25 mL, 2.68 mmol), anisidine
(5b, 0.32 g, 2.68 mmol), 2-propyn-1-yl-2,3,4,6-tetra-O-acetyl-b-
D
-
Qui-C), 99.7 (1C, Ano-C), 61.8–73.8 (6C, Sacc-C), 56.1 (1C, Qui-
OCH3), 55.9 (1C, Qui-OCH3), 55.5 (1C, Qui-OCH3), 20.3–20.6 (4C,
Ace-CH3). Anal. Calcd for C33H37NO13 (655.23): C, 60.45; H, 5.69;
N, 2.14. Found: C, 60.76; H, 5.83; N, 2.51.
D
-
glucopyranoside (6b, 0.84 g, 2.28 mmol) and CuCl (0.07 g,
0.68 mmol) in 10 mL of THF afforded compound 7d as an oily li-
quid (0.82 g, 61%); 1H NMR (300 MHz, CDCl3): dH 7.90–8.16 (m,
3H, Qui-H), 7.39–7.55 (m, 6H, Qui-H), 5.06–5.36 (m, 3H, Sacc-H),
4.58 (d, 1H, J = 7.8 Hz, H-1), 4.29 (s, 2H, CH2), 4.03–4.24 (m, 2H,
Sacc-H), 3.97 (s, 3H, Qui-OCH3), 3.77–3.79 (m, 1H, Sacc-H), 2.02–
2.17 (m, 12H, Ace-H). dC 169.5–171.2 (4C, Ace-C@O), 139.3–158.1
(5C, Qui-C), 114.7–132.1 (10C, Qui-C), 98.1 (1C, Ano-C), 61.9–73.2
(6C, Sacc-C), 55.6 (1C, Qui-OCH3), 20.6–20.8 (4C, Ace-CH3). Anal.
Calcd for C31H33NO11 (595.21): C, 62.51; H, 5.58; N, 2.35. Found:
C, 62.36; H, 5.69; N, 2.52.
Acknowledgments
Authors acknowledge CSIR, New Delhi for the financial support.
We also acknowledge Professor C.P. Rao, Department of Chemistry,
IIT Bombay, Mumbai for his valuable suggestions. T.M.D. thanks
DST, New Delhi for 300 MHz NMR spectrometer under the FIST
scheme to the Department of Organic Chemistry, University of Ma-
dras. K.K.K. thanks CSIR, New Delhi for a research fellowship.
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A
D
and CuCl (0.07 g, 0.68 mmol) in 10 mL of THF afforded compound
7e as an oily liquid (0.74 g, 52%); 1H NMR (300 MHz, CDCl3): dH
7.74–8.13 (m, 4H, Qui-H), 7.10–7.38 (m, 4H, Qui-H), 4.93–5.32
(m, 4H, Sacc-H), 4.56 (d, 1H, J = 7.8 Hz, H-1), 4.35 (s, 2H, CH2),
4.07–4.34 (m, 2H, Sacc-H), 3.90 (s, 3H, Qui-OCH3), 3.85 (s, 3H,
Qui-OCH3), 1.99–2.16 (m, 12H, Ace-H). dC 169.3–170.6 (4C, Ace-
C@O), 140.5–160.6 (5C, Qui-C), 110.2–132.0 (10C, Qui-C), 99.4
(1C, Ano-C), 61.8–73.8 (6C, Sacc-C), 55.5 (1C, Qui-OCH3), 55.3 (1C,
Qui-OCH3), 20.3–20.7 (4C, Ace-CH3). Anal. Calcd for C32H35NO12
(625.22): C, 61.43; H, 5.64; N, 2.24. Found: C, 61.12; H, 5.59; N,
2.58.
4.1.6. 2-(3,4-Dimethoxyphenyl)-6-methoxy-4-((2,3,4,6-tetra-O-
acetyl-b-
mixture of 3,4-dimethoxybenzaldehyde (4d, 0.44 g,
2.68 mmol), anisidine (5b, 0.32 g, 2.68 mmol), 2-propyn-1-yl-
2,3,4,6-tetra-O-acetyl-b- -glucopyranoside (6b, 0.84 g, 2.28 mmol)
D-glucopyranosyloxy)methyl)quinoline (7f)
A
D
and CuCl (0.07 g, 0.68 mmol) in 10 mL of THF afforded compound
7f as an oily liquid (0.77 g, 51%); 1H NMR (300 MHz, CDCl3): dH
7.65–8.10 (m, 3H, Qui-H), 7.35–7.39 (m, 1H, Qui-H), 6.98–7.13
(m, 3H, Qui-H), 5.16–5.43 (m, 3H, Sacc-H), 4.65–5.01 (m, 2H,
Sacc-H), 4.57 (d, 1H, J = 7.8 Hz, H-1), 4.36 (s, 2H, CH2), 4.13–4.35
(m, 1H, Sacc-H), 4.07 (s, 3H, Qui-OCH3), 3.96 (s, 3H, Qui-OCH3),
3.94 (s, 3H, Qui-OCH3), 2.01–2.11 (m, 12H, Ace-H). dC 169.3–
170.6 (4C, Ace-C@O), 144.2–157.6 (5C, Qui-C), 114.2–140.6 (10C,
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