Regioselective facile one-pot Friedl?nder synthesis of sugar-based heterocyclic biomolecules

Article abstract of DOI:10.1016/j.carres.2010.07.016

Regioselective facile one-pot synthesis of 16 different sugar-based quinoline, naphthyridine, and xanthone derivatives is reported. The compounds are characterized by NMR spectroscopy and elemental analysis. The β-Anomeric form of the sugar moiety was ide

Full text of DOI:10.1016/j.carres.2010.07.016

Carbohydrate Research 345 (2010) 1988–1997
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Regioselective facile one-pot Friedländer synthesis of sugar-based
heterocyclic biomolecules
Subbiah Nagarajan a, Pandian Arjun b, Nanjian Raaman b, Thangamuthu Mohan Das a,
*
a Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
b Fungal Biotechnology, Natural Products and Plant Tissue Culture Laboratory, Centre for Advanced Studies in Botany, 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:
Regioselective facile one-pot synthesis of 16 different sugar-based quinoline, naphthyridine, and
xanthone derivatives is reported. The compounds are characterized by NMR spectroscopy and elemental
analysis. The b-Anomeric form of the sugar moiety was identified from 1H NMR studies. Antimicrobial
studies of these sugar–heterocyclic derivatives, 3a, 3b, 3f, 5c, 7a, 7b, and 7c show excellent activity
against different microbes.
Received 2 July 2010
Accepted 8 July 2010
Available online 11 July 2010
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
b-C-Glycosylic ketones
Friedländer condensation
Quinolines
Naphthyridines
Xanthones
Antimicrobial activity
1. Introduction
quinazoline, and 1,8-naphthyridine derivatives have been found
to be potent drugs that are selective toward the adenosine antag-
The chemistry of nitrogen heterocycles, such as lactam, pyrrole,
indole, and quinoline derivatives, has been extensively studied for
more than 10 decades. The interest in these compounds is due, in
part, to the diversity of biological activities and pharmaceutical
applications found among these compounds (Fig. 1).1–8 Some of
the natural products having 2-arylated quinolines are present in
the nature and occur in the structures of 5-lipoxygenase inhibi-
tors,9 leucotriene antagonists,10 and LTD4 receptor antagonists
and other biologically active molecules.11 Among the different het-
erocyclic derivatives reported in the literature, quinoline-based
derivatives have been found to act as antimalarial,12–14 antibacte-
rial,15 antiasthmatic, antihypertensive, and anti-inflammatory
drugs.16 Quinolines also play an important role as antioxidants
and dyes. In addition to medical and industrial applications, poly-
quinoline derivatives are found to undergo hierarchical self-assem-
bly into nano- and meso-structures with enhanced electronic and
photonic properties.17,18 In general, adenosine-based nucleobases
and their derivatives exhibit a wide variety of physiological ac-
tions, including central nervous system depression, lowering of
blood pressure, inhibition of lipolysis, and platelet aggregation.19–24
Some of the heterocyclic derivatives such as isoquinoline,
onists.25–27 Xanthones are secondary metabolites found in higher
plant families like fungi and lichens, and these compounds exhibit
interesting pharmaceutical properties, such as antibacterial, anti-
inflammatory, antiviral, and anticancer activities.28–34 Moreover,
sugar-based chromen-4-ones (Fig. 1) isolated from olive and mar-
ine organisms exhibit a superior antimicrobial activity, and these
compounds also act as inhibitors of HIV cDNA integrase.35,36 Thus
new synthetic route to quinolines, xanthones, and naphthyridines
could have a major impact on the potential applications of these
compounds. The Friedländer reaction is one of the most important
methods for synthesizing pyridines, quinolines, naphthyridine, and
xanthones, but the major drawback is that unsymmetrical ketones
give both regioisomeric products.37 Herein, we report a novel,
highly regioselective Friedländer reaction for the synthesis of su-
gar–quinoline, –naphthyridine, and –xanthone derivatives. The in-
creased resistance to antibiotics represents the main factors
justifying the need to find and/or develop new antimicrobial
agents against human pathogens. Noteworthy, new and structur-
ally unusual lead structures for the development of antibiotics
are often found based on the screening of natural products and
their analogs.38 Even though a wide range of antibiotics are re-
ported in the literature,38 sugar-based antibiotics have greater im-
pact on the scientific society. In a continuation of our ongoing
research in the field of carbohydrate chemistry,39–44 we herein
report a facile one-pot regioselective synthesis of three different
sugar–heterocyclic derivatives.
* Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494.
E-mail address: tmdas_72@yahoo.com (T.M. Das).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.07.016

S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
1989
Figure 1. Representative examples of heterocyclic natural product motifs.
Table 1
2. Results and discussion
Optimization of Friedländer condensation of b-C-glycosylic ketones
2.1. Synthesis of b-C-glycosylic ketones
Entry
Solvent
Catalyst (25%)
Reaction time
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
EtOH
MeOH
DCM
H2O
CH3CN
DMSO
MeOH + DCM
EtOH + DCM
CH3CN + DCM
MeOH + DCM
MeOH + DCM
MeOH + DCM
MeOH + DCM
MeOH + DCM
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
TEA
24
24
24
48
36
48
10
14
18
24
5
35
46
15
4,6-O-Butylidene-
cosebyadoptingtheliteratureprocedure.45,46 b-C-Glycosylicketones,
such as 1-(4,6-O-butylidene-b- -glucopyranosyl)- (1a), 1-(b- -gluco-
pyranosyl)- (1b), 1-(b- -xylopyranosyl)- (1c), 1-(b- -galactopyrano-
syl)- (1d), 1-(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyl)- (1e),
1-(2,3,4-tri-O-acetyl-b- -xylopyranosyl)- (1f), and 1-(2,3,4,6-tetra-
O-acetyl-b- -mannopyranosyl)-propan-2-ones (1g), were synthe-
sized by Knoevenagel condensation of 2,4-pentadienone with
4,6-O-butylidene- -glucopyranose, -glucose, -xylose, and -galact-
ose, respectively, followed by acetylation of the free hydroxyl
group.47–49 Although the synthesis of b-C-glycosylic ketones of
per-O-acetylated derivatives is described in the literature,47–49 in
the present report, we have extended the methodology to partially
protected sugar derivatives.
D-glucopyranose was synthesized from D-glu-
a
—
D
D
20
24
78
57
52
39
D
D
D
D
D
b
NaOH
KOH
Pyridine
Piperidine
—
—
b
D
D
D
D
5
12
12
36
39
a
No reaction.
Decomposed product was obtained.
b
The Friedländer condensation of b-C-glycosylic ketones (1a–g)
with 2-amino-3,5-dibromobenzaldehyde (2) was carried out sepa-
rately at appropriate temperature in the presence of pyrrolidine
(25% equiv) as an organocatalyst (Table 2). Since the b-C-glycosylic
ketone is an unsymmetrical ketone, it regioselectively forms
2-substituted quinoline derivatives (3a–g). Among the seven differ-
ent sugar–quinolines synthesized, compound 3a exhibited a critical
gelation concentration (CGC = 2.0%) in ethanol and methanol sol-
vent. The Friedländer condensation was carried out with different
sugar derivatives, which resulted in the expected sugar–quinoline
derivatives in good yields (62–78%). The formation of the b-anomer-
ic product was confirmed by using 1H NMR studies (Ano-H, d 3.6–
5.0 ppm; J = 9.5–11.0 Hz) (Table 2).
2.2. Synthesis of sugar–quinoline derivatives
In the original form for the synthesis of quinoline, pyridine, naph-
thyridine, and xanthone derivatives, the Friedländer reaction con-
sisted of the reaction between an aromatic o-aminoaldehyde and an
aldehyde or ketone bearing an a-CH2 functionality. Though several
alternative routes for the synthesis of quinoline and substituted quin-
olines are known in the literature, their synthesis using the Friedlän-
der method seems to have created significant impact.50 To optimize
the reaction conditions, Friedländer condensations of 1-(4,6-O-butyl-
idene-b-D-glucopyranosyl)propan-2-one with an aromatic o-amino-
aldehyde, 2-amino-4,5-dibromobenzaldehyde in different solvents
under the influence of various catalysts were carried out at ambient
temperature (Table 1). In the present study, 1:3 CH2Cl2–MeOH and
pyrrolidine (25%) are the best solvent and organocatalyst, respec-
tively, which serve to promote the reaction resulting in yields of
72%. Whereas, other bases, such as, Et3N, NaOH, KOH, piperidine,
and pyridine, resulted in yields that were less than 40%.
2.3. Synthesis of sugar–naphthyridine derivatives
Sugar-based naphthyridines (5a–e) were synthesized from the
corresponding b-C-glycosylic ketones 1a and 1c–f with 2-amino-
3-pyridinecarboxaldehyde. Among the three different aromatic
aminoaldehydes used for the synthesis of sugar heterocyclics

1990
S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
Table 2
Synthesis of sugar–quinoline derivatives 3a–g
Br
O
Br
H2N
O
Pyrrolidine (25%)
RO
CH3
+
RO
N
1:3 CH2Cl2−MeOH
Br
O
OHC
Br
1a−g
3a−g
2
3
Yield of 3a–g in mga (%)
d (H-10) Ano-H/ppm ( JH1 –H2 /Hz)
0
0
Entry
Sugar part (1/3)
b-C-Glycosylic ketones (mg)
Time (h)
C3H7
O
H
O
O
1
1a (274)
10
403 (78)
3.77–3.88 (9.3)
HO
OH
3a
OH
O
HO
HO
2
1b (220)
12
332 (72)
3.74–3.81 (—b)
OH
3b
O
HO
HO
3
4
1c (190)
1d (220)
13
12
315 (73)
315 (68)
3.84–3.89 (10.8)
OH
3c
OH
HO
HO
O
3.64 (—b)
OH
3d
OAc
O
AcO
5
6
7
1e (388)
1f (316)
1g (388)
18
18
18
455 (72)
372 (67)
390 (62)
4.16–4.22 (9.5)
4.94–5.00 (—b)
3.90–4.09 (—b)
AcO
OAc
O
3e
3f
AcO
AcO
OAc
OAc
AcO
AcO
O
OAc
3g
a
Isolated yield after flash column chromatography.
Anomeric proton peaks overlapped with sugar skeletal proton peaks.
b
(2-amino-3-pyridinecarboxaldehyde, 2-amino-3-chromonecarbox-
aldehyde, and 2-amino-3,5-dibromobenzaldehyde), 2-amino-3-
pyridinecarboxaldehyde reacts more readily with b-C-glycosylic
ketones (Table 3). The formation of sugar-based naphthyridine
derivatives (5a–e) was identified from the 1H and 13C NMR studies.
The 1H NMR spectra of compounds 5a and 5b exhibited large
coupling constants (ꢀ9–12 Hz) for the H-10 signals indicating a
trans-diaxial orientation of H-10, and H-20 as it is expected for
expected sugar–chromeno[2,3-b]pyridin-5-ones. Increasing the
temperature to 70 °C led to the formation of the sugar–chro-
meno[2,3-b]pyridin-5-ones 7a–d in moderate yields (ꢀ70%) (Ta-
ble 4). In the case of sugar–quinoline and –naphthyridine
compounds, the expected products were obtained at ambient
temperature with less reaction time. Sugar–xanthone derivatives
were obtained at higher temperature and prolonged reaction time
and this may be attributed to the less reactive nature of the 2-
amino-3-chromonecarboxaldehyde with b-C-glycosylic ketones.
b-D-configured glucopyranose moiety (Table 3).
2.4. Synthesis of sugar–xanthone derivatives
2.5. Antimicrobial activity of sugar–quinoline, –naphthyridine,
and –xanthone derivatives
The reaction of 2-amino-3-chromonecarboxaldehyde (6) with
1-(4,6-O-butylidene-b-
D
-glucopyranosyl)-propan-2-one (1a) at
A screening of antibacterial activities with two Gram-positive
ambient temperature did not result in the formation of the
bacteria, Staphylococcus aureus (MTCC-98) and Bacillus subtilis

S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
1991
Table 3
Synthesis of sugar–naphthyridine derivatives 5a–e
O
H2N
N
O
RO
CH3
Pyrrolidine (25%)
1:3 CH2Cl2−MeOH
+
RO
N
N
O
OHC
1a, 1c f
−
4
5a−e
3
Yield of 5a–e in mga (%)
d (H-10) Ano-H /ppm ( JH1 –H2 /Hz)
0
0
Entry
Sugar part (1/5)
b-C-Glycosylic ketones (mg)
Time (h)
C3H7
O
H
O
O
1
1a (274)
7
340 (94)
3.54 (8.9)
HO
OH
5a
O
HO
HO
2
3
1c (220)
1d (190)
8
6
274 (90)
226 (82)
3.88 (12.3)
OH
5b
OH
HO
HO
O
2.93–3.82 (—b)
OH
5c
OAc
O
AcO
4
5
1e (388)
1f (316)
12
10
405 (85)
310 (77)
3.57–3.64 (—b)
4.90–4.96 (—b)
AcO
OAc
5d
5e
O
AcO
AcO
OAc
a
Isolated yield after flash column chromatography.
Anomeric proton peaks overlapped with sugar skeletal proton peaks.
b
(MTCC-441),andthreeGram-negativebacteria, Klebsiellapneumoniae
(MTCC-109), Pseudomonas aeruginosa (MTCC-1688), and Proteus vul-
garis (MTCC-742), was performed. All 16 different sugar-based het-
erocyclic derivatives showed various levels of inhibitory effects
against human pathogenic bacteria (Figs. 1–3). The antimicrobial
activities of these compounds were dose dependent and were found
sugar–quinoline derivatives led to a decrease in antimicrobial
activity. Among the 16 derivatives tested for antimicrobial activity,
compounds, 3a, 3b, 3f, 5c, 7a, 7b, and 7c showed activity against
P. vulgaris. If we made changes in theheterocyclic part, the compound
would show drastic changes in bioactivities, which implies that the
activity depends upon the type of sugar and heterocyclic moieties.
to be significant at 100 lg/mL concentration.
3. Conclusions
Among the seven sugar–quinoline derivatives studied, com-
pounds 3a and 3b inhibit the growth of B. subtilis, S. aureus, and
P. vulgaris to a greater extent in comparison with other compounds.
The Gram-negative human pathogenic bacteria K. pneumoniae
was remarkably inhibited by compound 3c, whereas all other
sugar–xanthone derivatives exert a moderate activity toward all
five bacteria tested. A plot of percentage of inhibition by various
bacterial strains is given in Figures 2–4. Further, compounds
3a, 3b, and 5c were found to be superior to the commercial antibi-
otic tetracycline in controlling Gram-negative bacteria such as
K. pneumoniae (MTCC-109), P. aeruginosa (MTCC-1688), and
P. vulgaris (MTCC-742). Compounds 3b and 5c were found to be
superior antibiotics against S. aureus, a Gram-positive bacterium.
In addition to this, most of the compounds showed significant anti-
microbial activity. Thus, the antimicrobial activity of sugar-based
heterocyclic biomolecules depends on both the sugar and the
heterocyclic moieties. Acetylation of free hydroxyl group in the
In conclusion, we have regioselectively synthesized the 16
different sugar-based quinoline, naphthyridine, and xanthone
derivatives. Heterocyclic moieties linked with sugar through a
methylene group provide flexibility to the sugar–heterocyclic deriv-
atives as observed in the case of sugar-based b-lactam derivatives.51
Based on the comparative synthetic studies, one can conclude that
2-amino-3-pyridinecarboxaldehyde reacts more readily than the
2-amino-3-chromonecarboxaldehyde and 2-amino-3,5-dibromo-
benzaldehyde. All the sugar-based heterocyclic derivatives synthe-
sized by the Friedländer condensation method exist in b-anomeric
form. Among the various sugar–heterocyclic derivatives synthe-
sized and studied, sugar–quinoline derivative 5a exhibits gelation
properties. Biological studies show that compounds 3a, 3b, 3f, 5c,
7a, 7b, and 7c possess better antibacterial activity against different
microbes than other compounds.

1992
S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
Table 4
Synthesis of sugar–xanthone derivatives 7a–d
O
O
H2N
O
O
RO
N
O
O
RO
CH3
+
Pyrrolidine (25%)
1:3 CH2Cl2−MeOH
OHC
O
1a, 1c, 1d, 1f
6
7a d
−
3
Yield of 7a–d in mga (%)
d (H-10)/ppm ( JH1 –H2 /Hz)
0
0
Entry
Sugar part (1/7)
b-C-Glycosylic ketones (mg)
Time (h)
C3H7
O
H
O
O
1
1a (274)
24
320 (75)
3.73–3.85 (—b)
HO
OH
7a
O
HO
HO
2
3
4
1c (220)
1d (190)
1f (316)
18
22
18
260 (70)
226 (66)
250 (68)
4.24 (5.7)
OH
7b
OH
HO
HO
O
3.69–3.75 (10.7)
3.68–3.73 (10.7)
OH
7c
O
AcO
AcO
OAc
7d
a
Isolated yield after flash column chromatography.
Anomeric proton peaks overlapped with sugar peaks.
b
30
25
20
15
10
5
a
b
c
d
e
f
g
0
B. subtilis
S. aureus
K. pneumoniae P. aeruginosa
P. vulgaris
Bacterial strains
Figure 2. Antibacterial activity of sugar–quinoline derivatives at 100 lg/mL concentration: (a) 3a; (b) 3b; (c) 3c; (d) 3d; (e) 3e; (f) 3f; and (g) 3g.

S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
1993
20
15
10
5
a
b
c
d
e
0
B. subtilis
S. aureus
K. pneumoniae P. aeruginosa P. vulgaris
Bacterial strains
Figure 3. Antibacterial activity of sugar–naphthyridine derivatives at 100
lg/mL concentration: (a) 5a; (b) 5b; (c) 5c; (d) 5d; and (e) 5e.
20
18
16
14
12
10
8
a
b
c
d
6
4
2
0
B. subtilis
S. aureus
K. pneumoniae P. aeruginosa
P. vulgaris
Bacterial strains
Figure 4. Antibacterial activity of sugar–xanthone derivatives at 100
l
g/mL concentration: (a) 7a; (b) 7b; (c) 7c; and (d) 7d.
India, with high purity and were used without any further purifica-
tion. Acetic anhydride was purchased from Fischer Chemcials Pvt.
Ltd, India. Column chromatography was performed on silica gel
(100–200 mesh). NMR spectra were recorded on a Bruker DRX
300 MHz instrument in CDCl3, D2O, or CDCl3 (with a few drops of
DMSO-d6). Chemical shifts were referenced to internal TMS. Ele-
mental analysis was performed by using a Perkin–Elmer 2400 ser-
ies CHNS/O analyser. While assigning the spectral data, several
abbreviations were used, and these include ‘Ar’ for aromatic,
‘Ace’ for acetal, ‘Sac’ and H-10–H-60 for saccharide, and Ha and Hb
for the methylene protons that connect between the sugar and
the heterocyclic moieties.
4. Experimental section
4.1. General methods
D
-Glucose, D-xylose, D-galactose, 2-amino-3-pyridinecarboxal-
dehyde, 2-amino-3-chromonecarboxaldehyde, and 2-amino-3,5-
dibromobenzaldehyde used for the synthesis were obtained from
Sigma–Aldrich Chemicals Pvt. Ltd, USA, and were of high purity.
Butyraldehyde and organocatalysts pyrrolidine, triethylamine,
NaOH, KOH, piperidene, and pyridine were obtained from SRL, In-
dia. Other reagents, such as hydrochloric acid, sodium hydrogen-
carbonate, and solvents (AR Grade), were obtained from Sd-fine,

1994
S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
4.2. Physicochemical and spectral data for 1-(4,6-O-butylidene-
(C-30), 78.0 (C-10), 73.6 (C-20), 70.4 (C-40), 61.6 (C-60), 41.0 (CH2-
Ar). Anal. Calcd for C16H17Br2NO5: C, 41.50; H, 3.70; Br, 34.51; N,
3.02. Found: C, 41.02; H, 3.93; N, 3.28.
b-D
-glucopyranosyl)propan-2-one (1a)
Compounds 1b–g were synthesized by adopting the procedure
reported in the literature,47–49 and the purity of these samples
4.3.3. Physicochemical and spectral data for 2-(b-D-
was found to be satisfactory. The synthetic procedure for 1a is as
xylopyranosylmethyl)-6,8-dibromoquinoline (3c)
follows: To a solution of 4,6-O-butylidene-
D
-glucopyranose 2.34 g
Yield: 73% as white solid; mp 198–200 °C; 1H NMR (CDCl3 +
DMSO-d6): d 8.10 (s, 1H, Ar-H), 8.04 (d, J = 8.4 Hz, 1H, Ar-H), 7.97
(s, 1H, Ar-H), 7.48 (d, J = 8.1 Hz, 1H, Ar-H), 4.81 (s, 1H, Sac-OH),
4.50 (s, 2H, Sac-OH), 3.84–3.89 (dd, J = 4.5 Hz, J = 10.8 Hz, 1H,
Sac-H), 3.76 (t, J = 7.1 Hz, 1H, Sac-H), 3.43–3.58 (m, 3H, Sac-H),
3.29–2.98 (m, 3H, Sac-H, Ha, Hb). 13C NMR (CDCl3 + DMSO-d6): d
166.2 (Ar-C), 148.0 (Ar-C), 140.4 (Ar-C), 140.1 (Ar-C), 134.3
(Ar-C), 133.5 (Ar-C), 130.2 (Ar-C), 129.1 (Ar-C), 123.5 (Ar-C), 84.2
(C-30), 83.5 (C-10), 78.5 (C-50), 75.0 (C-20), 74.7 (C-40), 46.2 (CH2-
Ar). Anal. Calcd for C15H15Br2NO4: C, 41.60; H, 3.49; Br, 36.90; N,
3.23. Found: C, 42.01; H, 3.10; N, 3.06.
(10.0 mmol) in 1:9 H2O–THF were added NaHCO3 (4 equiv) and
2,4-pentadienone (2 equiv). The reaction mixture was stirred at re-
flux temperature for 36 h and then cooled to room temperature.
The resultant mixture was filtered, and the residue was washed
well with CH2Cl2. The pale-yellow residue thus obtained was puri-
fied by column chromatography to get the expected product 1a.
(4:6 hexane–EtOAc): Yield: 85%; mp 102–104 °C; 1H NMR (CDCl3):
d 4.44–4.47 (t, J = 5.1 Hz, 1H, Ace-H), 4.03–4.08 (dd, J = 9.9 Hz,
J = 4.2 Hz, 1H, H-40), 3.72–3.79 (ddd, J = 3.3 Hz, J = 8.4 Hz,
J = 17.4 Hz, 1H, H-10), 3.61 (t, J = 8.7 Hz, 1H, H-30), 3.11–3.38 (m,
4H, H-20, H-50, H-60a, H-60b), 2.96–2.99 (m, 2H, Sac-OH), 2.79–
2.86 (dd, J = 3.9 Hz, J = 16.5 Hz, 1H, Hb), 2.54–2.62 (dd, J = 8.0 Hz,
J = 16.3 Hz, 1H, Ha), 2.13 (s, 3H, –CH3), 1.52–1.59 (m, 2H, –CH2),
1.31–1.39 (m, 2H, –CH2), 0.83–0.88 (t, J = 7.5 Hz, 3H, –CH3). 13C
NMR (CDCl3): d 207.3 (–OC–CH3),102.5 (Ace-C), 80.5 (C-50), 76.1
(C-30), 75.1 (C-10), 74.2 (C-20), 70.6 (C-40), 68.3 (C-60), 46.1(–CH2–
CO–CH3), 36.2 (–CH2–CO–CH3), 30.9 (CH2), 17.4 (CH2), 13.9 (CH3).
Anal. Calcd for C13H22O6: C, 56.92; H, 8.08. Found: C, 56.63; H, 8.26.
4.3.4. Physicochemical and spectral data for 2-(b-D-
galactopyranosylmethyl)-6,8-dibromoquinoline (3d)
Yield: 68% as
(CDCl3 + DMSO-d6):
a
white solid; mp 137–139 °C; 1H NMR
d 8.02 (d, J = 1.8 Hz, 1H, Ar-H), 7.85 (d,
J = 8.4 Hz, 1H, Ar-H), 7.89 (s, 1H, Ar-H), 7.47 (d, J = 8.4 Hz, 1H, Ar-
H), 4.77 (s, 1H, Sac-OH), 4.08 (s, 1H, Sac-OH), 3.92 (s, 2H, Sac-
OH), 3.64 (t, J = 5.4 Hz, 4H, Sac-H), 3.50–3.56 (m, 3H, Sac-H, 1H,
Hb), 3.16–3.24 (dd, J = 7.5 Hz, J = 14.7 Hz, 1H, Ha). 13C NMR
(CDCl3 + DMSO-d6): d 161.7 (Ar-C), 142.4 (Ar-C), 135.0 (Ar-C),
134.7 (Ar-C), 129.1 (Ar-C), 128.3 (Ar-C), 124.9 (Ar-C), 124.1 (Ar-
C), 118.0 (Ar-C), 78.8 (C-50), 77.9 (C-30), 74.6 (C-10), 71.2 (C-20),
68.7 (C-40), 60.8 (C-60), 30.4 (CH2-Ar). Anal. Calcd for C16H17Br2NO5:
C, 41.50; H, 3.70; Br, 34.51; N, 3.02. Found: C, 41.08; H, 3.51; N,
3.24.
4.3. General procedure for the synthesis of quinolinylmethyl
pyranoses (3a–g)
To a solution of b-C-glycosylic ketone 1 (1.0 mmol) in 1:3
CH2Cl2–MeOH were added pyrrolidine (25%) and 2-amino-3,5-dib-
romobenzaldehyde (2) (1.2 mmol). After stirring at room tempera-
ture for a given period of time, the solvent was evaporated under
reduced pressure. The crude product was slurried with silica gel
and purified by flash column chromatography to get the corre-
sponding sugar–quinoline derivatives.
4.3.5. Physicochemical and spectral data for 2-(2,3,4,6-tetra-O-
acetyl-b-D-glucopyranosylmethyl)-6,8-dibromoquinoline (3e)
Yield: 72% as white solid; mp 102–104 °C; 1H NMR (CDCl3): d
8.13, (d, J = 2.1 Hz, 1H, Ar-H), 7.96 (d, J = 8.7 Hz, 1H, Ar-H), 7.92
(d, J = 2.1 Hz, 1H, Ar-H), 7.38 (d, J = 8.4 Hz, 1H, Ar-H), 5.28 (t,
J = 10.7 Hz, 1H, H-40), 5.0–5.12 (m, 2H, H-20, H-30), 4.33–4.37 (m,
1H, Sac-H-60b), 4.16–4.22 (dd, J = 5.4 Hz, J = 9.5 Hz, 1H, H-10),
3.98–4.03 (dd, J = 2.1 Hz, J = 12.0 Hz, 1H, H-60a), 3.68–3.73 (ddd,
J = 2.5 Hz, J = 5.1 Hz, J = 9.9 Hz, 1H, H-50), 3.20–3.25 (m, 2H, Ha,
Hb), 1.95–2.07 (m, 12H, 4{–OCOCH3). 13C NMR (CDCl3): d 170.5
(–C@O), 170.4 (–C@O), 169.8 (–C@O), 169.5 (–C@O), 159.3 (Ar-C),
143.5 (Ar-C), 135.7 (Ar-C), 135.3 (Ar-C), 129.4 (Ar-C), 128.7
(Ar-C), 125.8 (Ar-C), 124.2 (Ar-C), 119.2 (Ar-C), 76.6 (C-50), 75.8
(C-10), 74.4 (C-30), 71.8 (C-20), 68.8 (C-40), 62.2 (C-60), 40.5 (CH2-
Ar), 20.7, 20.6 (4{–OCOCH3). Anal. Calcd for C24H25Br2NO9: C,
45.66; H, 3.99; Br, 25.32; N, 2.22. Found: C, 45.32; H, 3.63; N, 2.45.
4.3.1. Physicochemical and spectral data for 2-(4,6-O-
butylidene-b-D-glucopyranosylmethyl)-6,8-dibromoquinoline
(3a)
Yield: 78% as a white solid; mp 160–162 °C; 1H NMR (CDCl3 +
DMSO-d6): d 8.14 (d, J = 1.8 Hz, 1H, Ar-H), 8.03 (d, J = 8.4 Hz, 1H,
Ar-H), 7.95 (d, J = 1.8 Hz, 1H, Ar-H), 7.41 (d, J = 8.4 Hz, 1H, Ar-H),
5.06 (d, J = 3.6 Hz, 1H, Sac-OH), 4.50 (t, J = 5.0 Hz, 1H, Ace-H),
4.11–4.16 (dd, J = 4.2 Hz, J = 11.5 Hz, 1H, H-40), 3.77–3.88 (ddt,
J = 4.8 Hz, J = 9.3 Hz, 2H, H-10, H-30), 3.49–3.31 (m, 6H, H-50, H-
60a, H-60b, H-2, Hb, Sac-OH), 3.19 (t, J = 8.9 Hz, 1H, Ha), 1.65–1.62
(m, 2H, –CH2), 1.38–1.45 (m, 2H, –CH2), 0.90 (t, J = 7.4 Hz, 3H,
–CH3). 13C NMR (CDCl3 + DMSO-d6): d 160.1 (Ar-C), 143.0 (Ar-C),
136.4 (Ar-C), 136.1 (Ar-C), 129.5 (Ar-C), 128.7 (Ar-C), 125.2
(Ar-C), 124.5 (Ar-C), 119.6 (Ar-C), 102.5 (Ace-C), 80.7 (C-50), 78.7
(C-30), 74.4 (C-10), 74.4 (C-20), 71.2 (C-40), 68.4 (C-60), 41.6 (CH2-
Ar), 36.2 (CH2), 17.4 (CH2), 13.9 (CH3). Anal. Calcd for
4.3.6. Physicochemical and spectral data for 2-(2,3,4-tri-O-
acetyl-b-D-xylopyranosylmethyl)-6,8-dibromoquinoline (3f)
Yield: 67% as a colorless syrup; 1H NMR (CDCl3): d 8.12 (d,
J = 1.8 Hz, 1H, Ar-H), 7.98 (d, J = 8.4 Hz, 1H, Ar-H), 7.93 (s, 1H, Ar-
H), 7.38 (d, J = 8.4 Hz, 1H, Ar-H), 5.21 (t, J = 9.4 Hz, 1H, H-50b),
4.94–5.00 (m, 1H, H-10), 4.83 (t, J = 9.51 Hz, 1H, H-50a), 4.02–4.08
(dd, J = 5.7 Hz, J = 11.1 Hz, 1H, H-30), 3.88–3.94 (ddd, J = 1.8 Hz,
J = 4.8 Hz, J = 18.6 Hz, 1H, H04), 3.30 (t, J = 11.0 Hz, 1H, H-20),
2.65–2.74 (dd, J = 9.0 Hz, J = 16.4 Hz, 1H, Hb), 2.44–2.50 (dd,
J = 2.4 Hz, J = 16.5 Hz, 1H, Ha) 2.03–2.18 (m, 9H, 3{–OCOCH3).
13C NMR (CDCl3): d 170.2 (–C@O), 169.9 (–C@O), 169.8 (–C@O),
159.4 (Ar-C), 143.6 (Ar-C), 135.7 (Ar-C), 135.5 (Ar-C), 129.4
(Ar-C), 128.8 (Ar-C), 125.8 (Ar-C), 124.1 (Ar-C), 119.1 (Ar-C), 74.4
(C-50), 73.6 (C-10), 71.8 (C-30), 69.2 (C-20), 66.7 (C-40), 45.4 (CH2-
Ar), 31.0, 20.6 (3{–OCOCH3). Anal. Calcd for C21H21Br2NO7: C,
45.10; H, 3.79; Br, 28.58; N, 2.50. Found: C, 45.63; H, 4.12; N, 2.82.
C20H23Br2NO5: C, 46.44; H, 4.48; Br, 30.90; N, 2.71. Found: C,
46.13; H, 4.55; N, 2.83.
4.3.2. Physicochemical and spectral data for 2-(b-D-
glucopyranosylmethyl)-6,8-dibromoquinoline (3b)
Yield: 72% as
a
white solid; mp 164–165 °C; 1H NMR
(CDCl3 + DMSO-d6): d 8.07 (s, 1H, Ar-H), 8.02 (d, J = 7.8 Hz, 1H,
Ar-H), 8.00 (s, 1H, Ar-H), 7.58 (d, J = 8.4 Hz, 1H, Ar-H), 4.99 (s,
1H, Sac-OH), 4.74 (s, 2H, Sac-OH), 3.74–3.81 (m, 2H, Sac-H),
3.56–3.69 (m, 3H, Sac-H) 3.49 (m, 2H, Sac-H) 3.10–3.23 (m, 3H,
Sac-H, Ha, Hb). 13C NMR (CDCl3 + DMSO-d6): d 161.5 (Ar-C),
142.7 (Ar-C), 135.1 (Ar-C), 134.7 (Ar-C), 129.2 (Ar-C), 128.3
(Ar-C), 124.8 (Ar-C), 124.0 (Ar-C), 118.0 (Ar-C), 79.5 (C-50), 78.2

S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
1995
4.3.7. Physicochemical and spectral data for 2-(2,3,4,6-tetra-O-
acetyl-b- -galactopyranosylmethyl)-6,8-dibromoquinoline (3g)
4.4.4. Physicochemical and spectral data for 2-(2,3,4,6-tetra-O-
acetyl-b- -glucopyranosylmethyl)-1,8-naphthyridine (5d)
D
D
Yield: 62% as a colorless syrup; 1H NMR (CDCl3): d 8.12 (s, 1H,
Ar-H), 7.97 (d, J = 8.4 Hz, 1H, Ar-H), 7.93 (d, J = 1.5 Hz, 1H, Ar-H),
7.41 (d, J = 8.4 Hz, 1H, Ar-H), 5.43 (t, J = 4.4 Hz, 1H, H-40), 5.02–
5.15 (m, 2H, H-20, H-30), 3.90–4.09 (m, 4H, H-60a, H-60b, H-1,
H-50), 2.75–2.84 (dd, J = 9.0 Hz, J = 16.4 Hz, 1H, Hb), 2.17 (dd,
J = 3.0 Hz, J = 16.5 Hz,1H, Ha), 1.98–2.04 (m, 12H, 4{–OCOCH3).
13C NMR (CDCl3): d 170.4 (–C@O), 170.3 (–C@O), 170.1 (–C@O),
170.0 (–C@O), 159.6 (Ar-C), 143.5 (Ar-C), 135.6 (Ar-C), 135.3 (Ar-
C), 129.4 (Ar-C), 128.7 (Ar-C), 125.7 (Ar-C), 124.2 (Ar-C), 119.1
(Ar-C), 74.3 (C-50), 74.2 (C-10), 71.8 (C-30), 69.0 (C-20), 67.6 (C-40),
61.4 (C-60), 45.5 (CH2-Ar), 20.7, 20.6, 20.5 (4{–OCOCH3). Anal.
Calcd for C24H25Br2NO9: C, 45.66; H, 3.99; Br, 25.32; N, 2.22. Found:
C, 46.02; H, 4.23; N, 2.63.
Yield: 85% as a white solid; mp 124–126 °C; 1H NMR (CDCl3): d
9.06 (s, 1H, Ar-H), 8.19 (d, J = 8.1 Hz, 1H, Ar-H), 8.09 (d, J 8.1 Hz, 1H,
Ar-H), 7.43 (d, J = 8.1 Hz, 2H, Ar-H), 5.14 (d, J = 9.3 Hz, 1H, H-40),
4.99 (t, J 9.15 Hz, 1H, H-20), 4.09–4.14 (dd, J = 5.1 Hz, J = 12.2 Hz,
2H, H-30, H-60b), 3.88 (d, J = 12.3 Hz, 1H, H-10), 3.52–3.56 (m, 1H,
H-60a), 3.22–3.45 (m, 3H, H-50, Ha, Hb), 1.87–2.77 (m, 12H, 4X–
OCOCH3). 13C NMR (CDCl3): d 170.5 (–C@O), 170.2 (–C@O), 170.0
(–C@O), 169.6 (–C@O), 162.3 (Ar-C), 156.4 (Ar-C), 153.3 (Ar-C),
137.2 (Ar-C), 136.9 (Ar-C), 124.3 (Ar-C), 121.9 (Ar-C), 121.4 (Ar-
C), 76.7 (C-50), 75.5 (C-10), 74.2 (C-30), 72.1 (C-20), 68.7 (C-40), 62.3
(C-60), 41.3 (CH2-Ar), 20.7and 20.6 (4X–OCOCH3). Anal. Calcd for
C23H26N2O9: C, 58.22; H, 5.52; N, 5.90. Found: C, 57.71; H, 5.84;
N, 5.53.
4.4. General methods for the synthesis of sugar–naphthyrine
derivatives 5a–e
4.4.5. Physicochemical and spectral data for 2-(2,3,4-tri-O-
acetyl-b-D-xylopyranosylmethyl)-1,8-naphthyridine (5e)
Yield: 77% as a colorless syrup; 1H NMR (CDCl3): d 9.04 (br, 1H,
Ar-H), 8.19 (d, J = 8.1 Hz, 1H, Ar-H), 8.11 (d, J = 8.4 Hz, 1H, Ar-H),
7.44–7.48 (q, J = 4.5 Hz, J = 7.7 Hz, 1H, Ar-H), 7.40 (d, J = 8.4 Hz,
1H, Ar-H), 5.16 (t, J = 9.3 Hz, 1H, H-50b), 4.90–4.96 (m, 2H, H-10,
H-50a), 4.08 (t, J = 8.1 Hz, 1H, H-30), 3.89–3.94 (dd, J = 5.4 Hz,
J = 11.0 Hz, 1H, H-40), 3.01–3.43 (m, 3H, H-20, Ha, Hb), 2.03–2.53
(m, 9H, 3X–OCOCH3). 13C NMR (CDCl3): d 170.2 (–C@O), 170.1
(–C@O), 169.9 (–C@O), 162.4 (Ar-C), 155.0 (Ar-C), 153.1 (Ar-C),
137.5 (Ar-C), 137.3 (Ar-C), 124.2 (Ar-C), 121.9 (Ar-C), 121.5 (Ar-
C), 77.7 (C-50), 73.7 (C-10), 72.2 (C-30), 69.3 (C-20), 66.5 (C-40), 41.3
(CH2-Ar), 20.7 and 20.6 (3X–OCOCH3).
To a solution of b-C-glycosylic ketone 1 (1.0 mmol) in 1:3
CH2Cl2–MeOH were added pyrrolidine (25%) and 2-amino-3-pyri-
dinecarboxaldehyde (3, 1.2 mmol). After stirring at room tempera-
ture for a given period of time, the solvent was evaporated under
reduced pressure. The crude product was slurried with silica gel
and purified by flash column chromatography to get the corre-
sponding sugar–naphthyrine derivatives.
4.4.1. Physicochemical and spectral data for 2-(4,6-O-
butylidene-b-D-glucopyranosylmethyl)-1,8-naphthyridine (5a)
Yield: 94% as a white solid; mp 174–176 °C; 1H NMR (CDCl3): d
9.06 (d, J = 3.6 Hz, 1H, Ar-H), 8.25 (d, J = 8.1 Hz, 1H, Ar-H), 8.16 (d,
J = 8.4 Hz, 1H, Ar-H), 7.54 (d, J = 8.4 Hz, 1H, Ar-H), 7.11–7.41 (m,
1H, Ar-H), 5.41 (s, 2H, Sac-OH), 4.51 (t, J = 5.0 Hz, 1H, Ace-H),
3.88–3.98 (m, 3H, Sac-H), 3.54 (t, J = 8.9 Hz, 1H, Sac-H), 3.33–3.41
(m, 2H, Sac-H), 3.07–3.25 (m, 3H, Sac-H), 1.47–1.64 (m, 2H, –
CH2), 1.28–1.40 (m, 2H, –CH2), 0.81 (t, J = 7.35 Hz, 3H, –CH3). 13C
NMR (CDCl3): d 165.2 (Ar-C), 153.6 (Ar-C), 152.9 (Ar-C), 138.4
(Ar-C), 137.9 (Ar-C), 125.2 (Ar-C), 122.2 (Ar-C), 121.8 (Ar-C),
102.5 (Ace-C), 80.6 (C-50), 76.0 (C-30), 74.5 (C-10), 74.6 (C-20), 70.9
(C-40), 68.4 (C-60), 41.4 (CH2-Ar), 36.3 (CH2), 17.5 (CH2), 13.9
(CH3). Anal. Calcd for C19H24N2O5: C, 63.32; H, 6.71; N, 7.77. Found:
C, 62.89; H, 6.24; N, 8.10.
4.5. General procedure for the synthesis of sugar–xanthone
derivatives 7a–d
To a solution of b-C-glycosylic ketone 1 (1.0 mmol) in 1:3
CH2Cl2–MeOH were added pyrrolidine (25%) and 2-amino-3-chro-
monecarboxaldehyde (4, 1.2 mmol). After stirring at 70 °C for a gi-
ven period of time, the solvent was evaporated under reduced
pressure. The crude product was slurried with silica gel and puri-
fied by flash column chromatography to get the corresponding su-
gar–xanthone derivatives.
4.5.1. Physicochemical and spectral data for 2-(4,6-O-
butylidene-b-D-glucopyranosylmethyl)-10H-chromeno[3,2-
4.4.2. Physicochemical and spectral data for 2-(b-
xylopyranosylmethyl)-1,8-naphthyridine (5b)
D
-
b]pyridin-10-one (7a)
Yield: 75% as a white solid; mp 218–220 °C; 1H NMR (CDCl3 +
DMSO-d6): d 8.47 (d, J = 7.8 Hz, 1H, Ar-H), 8.13 (t, J = 7.4 Hz, 1H),
7.81 (t, J = 7.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.37–7.45 (m, 2H,
Ar-H), 4.45 (t, J = 4.7 Hz, 1H, Ace-H), 3.73–3.85 (m, 4H, Sac-H),
3.41 (d, J = 13.2 Hz, 2H, Sac-H), 3.25–3.32 (m, 1H, Sac-H), 3.17 (d,
J = 9.3 Hz, 1H, Sac-H), 3.11 (d, J = 5.7 Hz, 2H, Sac-H, Hb), 2.81–
2.89 (dd, J = 9.3 Hz, J = 14.4 Hz, 1H, Ha), 1.15–1.48 (m, 2H, –CH2),
1.29–1.45 (m, 2H, –CH2), 0.85 (d, J = 7.2 Hz, 3H, –CH3). 13C NMR
(CDCl3 + DMSO-d6): d 176.5 (Ar-C), 165.8 (Ar-C), 159.3 (Ar-C),
155.1 (Ar-C), 136.4 (Ar-C), 135.4 (Ar-C), 125.9 (Ar-C), 124.4
(Ar-C), 121.7 (Ar-C), 121.1 (Ar-C), 118.1 (Ar-C), 114.1 (Ar-C),
101.4 (Ace-C), 80.5 (C-50), 79.5 (C-30), 74.4 (C-10), 74.1 (C-20), 70.2
(C-40), 67.6 (C-60), 35.9 (–CH2-Ar), 30.5 (CH2), 17.0 (CH2), 13.7
(CH3). Anal. Calcd for C23H25NO7: C, 64.63; H, 5.90; N, 3.28. Found:
C, 64.98; H, 6.27; N, 3.51.
Yield: 90% as a white solid; mp 196–198 °C; 1H NMR (DMSO-
d6): d 8.92 (br, 1H, Ar-H), 8.34 (d, J = 7.8 Hz, 1H, Ar-H), 8.27 (d,
J = 8.1 Hz, 1H, Ar-H), 7.50 (d, J = 8.4 Hz, 2H, Ar-H), 3.57–3.64 (m,
2H, Sac-H), 3.31–3.46 (m, 5H, Sac-H), 3.32 (t, J = 8.9 Hz, 1H, H-40),
3.12 (t, J = 8.9 Hz, 1H, H-20), 2.93 (t, J = 9.75 Hz, 2H, Ha, Hb). 13C
NMR (DMSO-d6): d 163.8 (Ar-C), 154.8 (Ar-C), 152.8 (Ar-C), 137.3
(Ar-C), 137.2 (Ar-C), 123.5 (Ar-C), 121.6 (Ar-C), 121.0 (Ar-C), 79.8
(C-30), 78.1 (C-10), 73.8 (C-50), 69.8 (C-20), 69.5 (C-40), 41.3 (CH2-
Ar). Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.84; N, 10.14. Found:
C, 61.31; H, 6.25; N, 10.33.
4.4.3. Physicochemical and spectral data for 2-(b-D-
galactopyranosylmethyl)-1,8-naphthyridine (5c)
Yield: 82% as a white solid; mp 212–214 °C; 1H NMR (D2O): d
8.68 (br, 1H, Ar-H), 7.98 (t, J = 10.3 Hz, 2H, Ar-H), 7.36 (d,
J = 8.1 Hz, 1H, Ar-H), 7.30 (br, 1H, Ar-H), 4.98 (t, J = 8.4 Hz, 1H,
Sac-H), 2.93–3.82 (m, 8H, Sac-H). 13C NMR (D2O): d 163.6 (Ar-C),
153.1 (Ar-C), 138.5 (Ar-C), 138.4 (Ar-C), 123.6 (Ar-C), 122.2 (Ar-
C), 121.4 (Ar-C), 79.2 (C-50), 78.5 (C-30), 74.0 (C-10), 71.0 (C-20),
69.1 (C-40), 61.1 (C-60), 40.6 (CH2-Ar). Anal. Calcd for C15H18N2O5:
C, 58.82; H, 5.92; N, 9.15. Found: C, 59.08; H, 6.27; N, 9.31.
4.5.2. Physicochemical and spectral data for 2-(b-D-
xylopyranosylmethyl)-10H-chromeno[3,2-b]pyridin-10-one
(7b)
Yield: 70% as a white solid; mp 185–187 °C; 1H NMR (CDCl3 +
DMSO-d6): d 8.50 (d, J = 7.8 Hz, 1H, Ar-H), 8.19 (d, J = 7.8 Hz, 1H,
Ar-H), 7.75 (t, J = 7.5 Hz, 1H, Ar-H), 7.55 (d, J = 8.4 Hz, 1H, Ar-H),

1996
S. Nagarajan et al. / Carbohydrate Research 345 (2010) 1988–1997
7.36–7.41 (m, 2H, Ar-H), 3.69–3.75 (dd, J = 5.1 Hz, J = 10.7 Hz, 1H,
H-10), 3.61–3.68 (m, 1H, Sac-H), 3.13–3.47 (m, 4H, Sac-H), 3.01 (t,
J = 10.7 Hz, 2H, Sac-H, Hb), 2.87–2.91 (dd, J = 9.3 Hz, J = 13.7 Hz,
1H, Ha). 13C NMR (CDCl3 + DMSO-d6): d 177.0 (Ar-C), 165.9 (Ar-
C), 159.3 (Ar-C), 136.4 (Ar-C), 135.1 (Ar-C), 125.9 (Ar-C), 124.1
(Ar-C), 121.5 (Ar-C), 121.1 (Ar-C), 117.9 (Ar-C), 114.1 (Ar-C), 79.2
(C-30), 78.3 (C-10), 73.6 (C-50), 69.6 (C-20), 69.5 (C-40), 40.9 (CH2-
Ar). Anal. Calcd for C18H17NO6: C, 62.97; H, 4.99; N, 4.08. Found:
C, 63.36; H, 5.29; N, 4.25.
Acknowledgments
The authors acknowledge UGC, New Delhi, India, for financial
support. T.M. thanks DST, New Delhi, for the 300 MHz NMR facility
under the DST-FIST programme to the Department of Organic
Chemistry, University of Madras, Guindy campus, Chennai, India.
S.N. thanks CSIR for SRF. We thank Dr. C. P. Rao, IIT Bombay, Mum-
bai, for valuable discussion.
Supplementary data
4.5.3. Physicochemical and spectral data for 2-(b-D-galactopyra-
nosylmethyl)-10H-chromeno[3,2-b]pyridin-10-one (7c)
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.07.016.
Yield: 66% as
a
white solid; mp 150–152 °C; 1H NMR
d 8.53 (d, J = 7.8 Hz, 1H, Ar-H), 8.24 (d,
(CDCl3 + DMSO-d6):
J = 7.5 Hz, 1H, Ar-H), 7.83 (t, J = 7.2 Hz, 1H, Ar-H), 7.61 (d,
J = 8.1 Hz, 1H, Ar-H), 7.43–7.52 (m, 2H, Ar-H), 4.48 (d, J = 5.7 Hz,
1H, Sac-H), 4.49 (d, J = 3.9 Hz, 1H, Sac-H), 4.24 (d, J = 5.7 Hz, 2H,
Sac-H), 3.33–3.65 (m, 7H, Sac-H), 2.98–3.06 (dd, J = 9.0 Hz,
J = 14.4 Hz, 1H, Sac-H). 13C NMR (CDCl3 + DMSO-d6): d 176.7 (Ar-
C), 166.4 (Ar-C), 159.2 (Ar-C), 155.1 (Ar-C), 136.1 (Ar-C), 135.1
(Ar-C), 125.9 (Ar-C), 124.2 (Ar-C), 121.7 (Ar-C), 121.1 (Ar-C),
117.9 (Ar-C), 113.9 (Ar-C), 78.9 (C-50), 78.2 (C-30), 74.7 (C-10),
71.0 (C-20), 68.6 (C-40), 60.6 (C-60), 40.8 (CH2-Ar). Anal. Calcd for
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