A concise pathway to synthesize a novel class of pyrido(2,3-d)pyrimidine-C- β-d-glycosides

Article abstract of DOI:10.1016/j.carres.2012.11.013

A concise pathway to synthesize a novel class of nine different pyrido(2,3-d)pyrimidine-C-β-d-glycosides is reported. Formation of Michael adduct as an intermediate followed by heterocyclization are the key steps and the products were characterized by different spectral studies. β-Anomeric forms of C-glycosides were assigned from ¹H NMR spectroscopy.

Full text of DOI:10.1016/j.carres.2012.11.013

Carbohydrate Research 368 (2013) 40–46
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A concise pathway to synthesize a novel class of pyrido(2,3-d)pyri-
midine-C-b-D-glycosides
⇑
Muniyappapillai Jeganathan Shanmugam, Thangamuthu Mohan Das
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 25, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A concise pathway to synthesize a novel class of nine different pyrido(2,3-d)pyrimidine-C-b-D-glycosides
Received 14 September 2012
Received in revised form 3 November 2012
Accepted 16 November 2012
Available online 29 November 2012
is reported. Formation of Michael adduct as an intermediate followed by heterocyclization are the key
steps and the products were characterized by different spectral studies. b-Anomeric forms of C-glycosides
were assigned from 1H NMR spectroscopy.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Pyrido(2,3-d)pyrimidine derivatives
N-Heterocycles
C-Glycosides
Sugar chalcones
1. Introduction
therapeutic profiles viz., solubility, in vivo stability, target-binding
affinity and cell permeability.13 Thus the studies pertaining to het-
In modern synthetic organic chemistry, development of a novel
and efficient method for the construction of several mono as well
as poly heterocyclic scaffolds is one of the current areas of research
interest.1 Pyrido(2,3-d)pyrimidine derivatives, being an important
class of N-heterocycles display several potential biological activi-
ties, such as tyrosine kinase inhibition,2 dihydrofolate reductase
inhibition,3 STa induced cGMP synthesis inhibition,4 anti-bacte-
rial,5 anti-inflammatory6 and in vitro cytotoxic activities.7 In par-
ticular, naturally occurring compounds viz., sangivamycin (1)
containing pyrrolo(2,3-d)pyrimidine nucleoside and its simple
homologue pyrido(2,3-d)pyrimidine nucleoside (2) were found to
possess anti-leukaemic activity (Fig. 1).8,9 Moreover, the beneficial
properties of basic and electron-withdrawing nature of N-hetero-
cyclic compounds make them a more attractive biological target
more effectively than carbocyclic compounds. In this connection
the anti-tumour activity of benz[a]anthraquinone chromophore
of 3,4-dihydro-8-hydrotetraphene-1,7,12(2H)-trione (3) was en-
hanced by modifying one of its aromatic methine groups to afford
3,4-dihydro-8-hydroxybenzo[j]phenanthridine-1,7,12(2H)-trione
(4) (Fig. 1)10 which possesses more potent anti-tumour activities.
Thus these structural motifs acquire great attention in the field
of pharmaceutical chemistry.
erocyclic carbohydrate derivatives with C-linkage have received
increasing attention not only among synthetic organic chemists
but also among medicinal chemists. Although the synthesis of sev-
eral pyrido(2,3-d)pyrimidine derivatives was carried out by differ-
ent synthetic strategies and reported in the literature,1,14–16 all
those methods lead to the formation of the core moiety linked with
aromatic systems. Among them, a few of the synthetic strategies
involve Michael addition of a-,b-unsaturated ketones with amino-
uracil, reaction of 2-amino-3-cyano-4,5,6-disubstitutedpyridines
with carbonyl compounds and a selective condensation of amino-
pyrimidine with propiophenone hydrochlorides. Therefore, by con-
sidering the importance of N-heterocyclic based C-glycosides
including other glycosides,17,18 viz., N-glycosylamine, O-glycosides
and their various biological and material applications, our present
study focuses on the concise pathway to synthesize the novel class
of pyrido(2,3-d)pyrimidine-C-b-D-glycosides. Moreover, to the best
of our knowledge this is the first report on studies on pyrido(2,3-
d)pyrimidine based C-glycosides.
2. Results and discussion
Aldol condensation of (4,6-O-butylidene-b-
syl)propan-2-one (5) with various substituted aromatic aldehydes
(6a–i) resulted in the formation of the corresponding -,b-unsatu-
D-glucopyrano-
Indeed, some of the carbohydrate derivatives like flavone C-gly-
cosides,11 from natural origins as well as the synthetic macrocyclic
lactones having a C-linkage12 were also reported to possess good
a
rated-C-b-glycosidic ketones (7a–i) in 80–95% yield (Scheme 1).
Although the synthesis and characterization of sugar chalcones,
7a, 7d, 7e and 7g were already reported in the literature,19 details
about compounds 7b, 7c, 7f, 7h and 7i are presented in the
⇑
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 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.11.013

M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
41
Table 1
O
O
O
N
NH2
N
NH2
N
H2N
O
Optimization of reaction condition for compound, 9a
H2N
HO
Entry
Solvent ratio of THF/EtOH
Condition
Temp (°C)
Yield (%)
N
N
a
N
1
2
3
4
5
6
7
8
0:1
0:1
0:1
1:0
1:0
1:0
0:1
1:0
1:1
2:1
3:1
KOH
NaOH
Et3N
KOH
NaOH
Et3N
NaOEt
NaOEt
NaOEt
NaOEt
NaOEt
60
60
60
rt
rt
rt
60
rt
rt
rt
rt
—
—
—
HO
a
O
a
OH OH
OH OH
32
32
(1)
(2)
b
—
—
a
O
O
O
O
58
60
63
73
9
10
11
N
OH
O
OH
O
a
Resulted in formation of decomposed product.
Reaction was not successful.
b
(3)
(4)
Figure 1. Molecular structures of 4-amino-7-(tetrahydro-3,4-dihydroxy-5-
(hydroxymethyl)furan-2yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide (1) and
its homologue, 4-amino-5,8-dihydroxy-8-(tetrahydro-3,4-dihydroxy-5-(hydroxy-
methyl)furan-2yl)-5-oxopyrido-[2,3-d]pyrimidine-6-carboxamide (2), 3,4-dihy-
dro-8-hydrotetraphene-1,7,12(2H)-trione (3) and 3,4-dihydro-8-hydroxybenzo[j]
phenanthridine-1,7,12(2H)-trione (4). Encircled shows the comparison between the
naturally occurring compound (1) with synthetic one (2) and also among the
synthetic derivatives (3 and 4).
percentage of yield for different pyrimidine sugar heterocyclic
derivatives (9a–i) are provided in Table 2.
Structural elucidation of the expected product formation was
established on the basis of its spectroscopic data. 1H NMR spectra
of
a-,b-unsaturated-C-b-glycosides (7a–i) showed the signals
around 7.30–6.59 ppm for alkenic proton (Alk-Ha), adjoining the
carbonyl group and 7.80–7.30 ppm for the alkenic proton (Alk-
Hb), adjoining the aromatic moiety their corresponding carbon
peaks in 13C NMR were observed in the region of 135.25–
120.27 ppm and 147.97–141.71 ppm respectively. Moreover the
H
CH3
H
O
CH3
O
O
R
R-CHO (6a-i)
O
O
O
CH3
HO
HO
Pyrrolidine, DCM
rt, 15-30min
OH
OH
(7a-i)
observation of
a larger coupling constant (J = 15.9–16.2 Hz)
O
O
showed the existence of ‘E’ isomeric forms in sugar chalcones. In
(5)
particular, 1H NMR spectral studies of the 7-(4,6-O-butylidene-b-
(80-95%)
D
-glucopyranosyl-1-methyl)-1,3-dimethyl-5-phenylpyrido(2,3-
(a)R=Ph, (b)R=4-OMePh, (c)R=4-MePh, (d)R=Piperonal, (e)R=3,4-di-OMePh,
(f)R=4-ClPh, (g)R=4-FPh, (h)R=3-BrPh, (i)R=Pyrrole,
d)pyrimidine-2,4-dione (9a) confirmed the formation of the pyri-
dopyrimidine core moiety by the appearance of a sharp singlet (d
6.91 ppm) corresponding to the methine proton and it was further
confirmed by the disappearance of doublet (d 6.78 ppm) corre-
sponding to the alkenic proton of sugar chalcone, (E)-1-(4,6-O-
Scheme 1. Synthesis of a-,b-unsaturated-C-b-glycosides.
experimental section. Pyrimidine based heterocyclic derivatives
(9a–i) were synthesized by the condensation of -,b-unsatu-
a
butylidene-b-D-glucopyranosyl)-4-phenylbut-3-en-2-one (7a). In
rated-C-b-glycosidic ketones (7a–i) with 6-amino-1,3-dimethyl-
uracil (8) (Scheme 2). In order to obtain the expected products in
good yield, the reaction was carried out using different bases, such
as KOH, NaOH, NaOEt, Et3N in different solvents, such as EtOH and
THF. The reaction condition was optimized to get 7-(4,6-O-butyli-
dene-b-D-glucopyranosyl-1-methyl)-1,3-dimethyl-5-phenylpyri-
do(2,3-d)pyrimidine-2,4-dione (9a) and the details about the
optimized reaction conditions are given in Table 1.
addition, NMR spectral analysis of all the sugar-heterocyclic deriv-
atives [9(a–i)] confirmed the formation of the pyridopyrimidyl
core. Appearance of a characteristic peak [1H NMR: singlet, d
7.58–6.75 ppm; 13C NMR: d 126.84–122.17 ppm] corresponding
to the ‘‘Py-CH’’ confirmed the presence of pyridopyrimidyl core
in all the products [9(a–j)]. Although the starting material 8 exhib-
ited two sharp singlets in the range of 3.32–3.18 ppm in 1H NMR
and 28.99–26.91 ppm in 13C NMR, the corresponding peaks in
the sugar-heterocyclic products were shifted to higher frequencies,
3.85–3.30 ppm in 1H NMR & 30.15–28.41 ppm in 13C NMR respec-
tively. Diastereotopic proton of the methylene group which links
Studies show that using sodium ethoxide as catalyst in THF/
EtOH (3:1) solvent mixture at room temperature resulted in bet-
ter yield (entry 11, Table 1). Spectral data, reaction time and
CH3
N
O
H
O
CH3
H
CH3
N
O
H2N
CH3
O
R
O
R
O
O
8
O
HO
O
HO
OH
(9 a-i)
OH
(7a-i)
NaOEt
N
O
N
THF/EtOH, rt
CH3
N
H3C
30-90min
(65-80%)
O
(a) R= Ph,
(b) R= 4-OMePh,
(c) R= 4-MePh
(d) R= Piperonal,
(e) R= 3,4-diOMePh
(f) R= 4-ClPh
(g) R= 4-FPh
(h) R= 3-BrPh
(i) R= Pyrrole
Scheme 2. Synthesis of pyrido(2,3-d)pyrimidine derivatives (9a–i).

42
M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
Table 2
Spectral data, reaction time and percentage of yield for different pyrimidine sugar heterocyclic derivatives (9a–i)
Entry
R 6/7/9(a–i)
NMR (d in ppm) 9
Reaction time
(min)
Yield (%) 9
1H [Py-CH]
13C [Py-CH]
1
6.92
122.68
30
35
73
a
2
3
4
5
6.83
6.91
6.79
6.75
122.79
122.78
122.17
122.86
82
81
72
79
OCH3
b
30
60
65
CH3
c
O
O
d
OCH3
OCH3
e
6
7
6.81
6.89
122.46
122.68
30
30
86
82
Cl
f
F
g
8
9
6.88
7.58
122.40
126.84
90
90
67
75
Br
h
N
H
i
pyridopyrimidyl core moiety and protected sugar in the products,
9(a–i) was found to appear at d.3.04–2.80 ppm as a doublet of dou-
blet and the corresponding 13C NMR spectra exhibited a peak at d
45.49–40.82 ppm further confirming the formation of the hetero-
cyclic core moiety. Moreover, the saccharide skeletal proton of su-
gar-chalcones showed peaks in the range of 5.29–2.95 ppm, the
corresponding sugar-heterocyclic products 9(a–i) appeared in the
region of d 5.30–3.12 ppm. The appearance of the anomeric proton
as a doublet of triplets at d 4.04–3.78 ppm with a large coupling
constant of J = 9.3–7.2 Hz supports the existence of a sugar moiety
in the b-anomeric form. This is further supported by the observa-
tion of peaks at d 75.39–70.67 ppm in the 13C NMR spectrum.
The condensation takes place between the chalcone moiety and
the amine group of the heterocycle. Such condensation does not al-
ter the chemical shift of the acetal proton. In addition the appear-
ance of quaternary carbon peaks for the sugar-heterocyclic
products 9(a–i) in the region of d 157.16–152.73 ppm, d 151.60–
147.82 ppm and d 107.89–106.18 ppm showed the presence of four
bridged quaternary carbons in the pyridopyrimidine core moiety.
Although the two carbonyl carbon peaks of the starting material
8 were observed in d 161.99 ppm and 151.57 ppm, in the corre-
sponding products 9(a–i) it was observed in the range of d
167.08–161.97 ppm and d 155.47–151.53 ppm. Furthermore the
FT-IR spectra of the sugar heterocyclic derivatives (9a–i) showed
bands around the region of 1713–1690, 1659–1628, 1597–1589
and 1558–1535 cmÀ1 which correspond to mC@O
, mC@O, mC@N, mC@C
groups confirming the formation of pyridopyrimidyl core moiety
and it was again proved from the disappearance of bands in the
range of 1744–1682 and 1628–1582 cmÀ1 which correspond
to mC@O, mC@C groups of the sugar chalcones (7a–i). Absorption
spectral studies of both pyridopyimidine derivatives [9b,c,f,i] and
their corresponding precursors [7b,c,f,i] showed that the
characteristic bands for the product around 323 and 375 nm
were absent in the precursor spectrum. Molar absorbance coeffi-
cients (emax) of the chalcone core moiety were observed around
16.2 Â 103 MÀ1 cmÀ1 whereas for the pyridopyrimidine core moi-
ety, it was observed around 34.0 Â 103 MÀ1 cmÀ1. Red shift of the
absorbance band (kmax) of the chalcones, which corresponds to

M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
43
the
p
–
p⁄ transition of enones has been observed in the range of
4.2. Synthesis of
a
-,b-unsaturated-C-b-glycosides (7a–i)
-,b-unsaturated-C-b-glycosidic compounds
320–350 nm to 323–382 nm, further confirming the product for-
mation. Thus the absorbance studies showed the formation of
the expected products (see Supplementary data for details). It
was presumed that the path of the reaction involves the formation
of Michael adduct as an intermediate which then subsequently
underwent heterocyclization to furnish the expected pyridopyrim-
idine derivatives. In general, the aromatic substrate bearing elec-
tron releasing group at the 4th position is known to activate
these types of reactions.20 Thus, the results corresponding to the
formation of these products in yield further proved the observed
trend (Table 2) that is, activation of these types of reactions by
the electron releasing groups such as –CH3, –OCH3, –Cl, –F at the
4th position of aromatic core moiety. In addition, the preliminary
investigation of sugar heterocyclic compounds such as 9c, 9f, 9g
and 9i towards the anti-oxidant activity using the literature re-
ported protocols21,22 exhibited the moderate anti-oxidant activi-
ties with maximum inhibitory activity of 65.28% for 9c and
minimum inhibitory activity of 51.89% for 9f (see Supplementary
data for details).
The synthesis of
a
7a, 7d, and 7e were carried out by using literature proce-
dures.19,28–30 Similar procedure was adopted for the synthesis of
the compounds 7(b–c) and 7(f–i). Spectral data and procedures
are as follows:
4.2.1. Physicochemical and spectral data for (E)-1-(4,6-O-
butylidene-b-
D
-glucopyranosyl)-4-(4-methoxy)phenylbut-3-en-
2-one (7b)
The reaction of (4,6-O-butylidene-b-
D
-glucopyranosyl)propan-
2-one (5) (1 mmol, 0.274 g) with p-methoxybenzaldehyde (6b)
(1.2 mmol, 0.163 g) in the presence of organo-catalyst such as pyr-
rolidine (30 mol %) using DCM as a solvent afforded the compound,
7b in 85% yield. Mp: 185–189 °C; 1H NMR (300 MHz, CDCl3 + DMSO-
d6, ppm): d 7.52–7.45 (m, 3H, Ar-H, Alk-Hb), 6.87 (d, 2H, J = 9 Hz, Ar-
H), 6.61 (d, 1H, J = 16.2 Hz, Alk-Ha), 4.49 (t, 1H, J = 5.1 Hz, Ace-H),
4.09–4.04 (dd, 1H, J = 3.9 Hz, J = 9.9 Hz, Sac-H), 3.91–3.80 (dt, 1H,
J = 3 Hz, J = 8.7 Hz, Ano-H), 3.80 (s, 3H, Ar-OCH3), 3.64 (t, 1H,
J = 8.7 Hz, Sac-H), 3.40–3.18 (m, 4H, Sac-H), 3.12–3.06 (m, 1H, Sac-
H), 2.85–2.77 (dd, 1H, J = 8.4 Hz, J = 7.5 Hz, CH2, Ha), 1.63–1.55 (m,
2H, CH2), 1.35 (q, 2H, J = 7.5 Hz, CH2). 0.86 (t, 3H, J = 7.5 Hz, CH3).
13C NMR (75 MHz, CDCl3 + DMSO-d6, ppm): d 198.01 (CO), 161.63
(Ar-C), 143.11 (Alk-CH), 130.08 (Ar-CH), 130.08 (Ar-CH), 127.06
(Ar-C), 124.26 (Alk-CH,), 114.40 (Ar-CH), 102.34 (Ace-CH), 80.49
(Sac-CH), 76.48 (Sac-CH), 75.14 (Sac-CH), 74.75 (Sac-CH), 70.57
(Sac-CH), 68.36 (Sac-CH2), 55.38 (Ar-OCH3), 43.27 (CH2), 36.24
3. Conclusion
In summary, a series of pyrido(2,3-d)pyrimidine-C-b-D-glyco-
sides were synthesized in 65–80% yield with an efficient synthetic
strategy accomplished by the formation of Michael adduct as an
intermediate followed by heterocyclization and characterized by
using NMR spectroscopic and elemental analyses. The existence
of b-anomeric forms of the products were studied through 1H
NMR spectroscopy. Functional group transformation was identified
by FT-IR studies. UV–visible spectral studies showed characteristic
bands corresponding to the heterocyclic core moiety. The present
study not only pioneers the novel class of compounds in carbohy-
drate chemistry but also provides an attractive and simple opera-
tional method for the construction of biological analogue
(CH2), 17.42 (CH2), 13.89 (CH3). IR
2954.73, 2869.87, 2360.70, 1712.66, 1627.80. Anal. Calcd for
21H28O7: C, 64.27; H, 7.19. Found: C, 64.18; H, 7.25.
t
(cmÀ1): 3502.47, 3394.97,
C
4.2.2. Physicochemical and spectral data for (E)-1-(4,6-O-
butylidene-b-
D
-glucopyranosyl)-4-(4-methyl)phenylbut-3-en-2-
one (7c)
The reaction of (4,6-O-butylidene-b-
D
-glucopyranosyl)propan-
pyrido(2,3-d)pyrimidine-C-b-D-glycosides as it is evidenced from
2-one (5) (1 mmol, 0.274 g) with p-methylbenzaldehyde (6c)
(1.2 mmol, 0.144 g) in the presence of organo-catalyst, such as pyr-
rolidine (30 mol %) using DCM as a solvent afforded the compound,
7c in 86% yield. Mp: 178–182 °C; 1H NMR (300 MHz,
CDCl3 + DMSO-d6, ppm,): d 7.67–7.48 (m, 3H, Ar-H, Alk-Hb); 7.30
(d, 2H, J = 7.5 Hz, Ar-H) 6.82 (d, 1H, J = 15.9 Hz, Alk-Ha), 4.65–4.62
(m, 1H, Ace-H), 4.21–4.18 (m, 1H, Sac-H), 4.04–3.98 (m, 1H, Ano-
H), 3.76 (t, 1H, J = 8.4 Hz, Sac-H), 3.53–3.32 (m, 4H, Sac-H), 3.28–
3.22 (m, 2H, Sac-H), 2.98–2.90 (dd, 1H, J = 8.1 Hz, J = 15.6 Hz, CH2,
Ha), 2.48 (s, 1H, CH3), 1.73–1.72 (m, 2H, CH2) 1.52 (q, 2H,
J = 7.2 Hz, CH2), 1.00 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (75MHZ,
CDCl3 + DMSO-d6, ppm): d 192.75 (CO), 137.88 (Ar-CH), 135.72
(Ar-C), 126.39 (Alk-CH), 124.38 (Ar-CH), 123.03 (Ar-CH), 120.27
(Alk-CH), 97.01 (Ace-CH), 75.24 (Sac-CH), 71.23 (Sac-CH), 69.82
(Sac-CH), 69.48 (Sac-CH), 65.31 (Sac-CH), 63.07 (Sac-CH2), 38.02
(CH2), 30.97 (CH2), 16.18 (Ar-CH3), 12.13 (CH2), 8.62 (CH3). IR
the preliminary biological investigation.
4. Experimental section
4.1. General methods
All aromatic aldehydes were purchased from Sigma Aldrich,
Bangalore, India. D-Glucose, butyraldehyde, acetylacetone, sodium
bicarbonate and sodium sulphate were obtained from SRL, India
with high purity. Sodium ethoxide was prepared through standard
procedure.23 Melting points were uncorrected. Dry solvents, such
as THF and absolute ethanol used in the reaction were purchased
from Sd-fine, India. The column chromatography was performed
on Silica Gel (100–200) mesh. 4,6-O-Butylidene-
D-glucopyranose
and (4,6-O-butylidene-b- -glucopyranosyl)propan-2-one (5) were
D
synthesized by adopting the literature procedure.24–28 NMR spec-
tra were recorded with a Bruker DRX 300 MHz spectrometer with
CDCl3 and DMSO-d6 as solvents. Chemical shift values are refer-
enced with internal TMS. ABB-Bomem FT-IR spectrometer was
used for recording IR spectra. Absorption studies were carried
out with the UV–visible spectrophotometer 1800 Shimabzu, Japan.
Elemental analysis was performed using Thermoquest microanaly-
ser. Optical Density was measured using Eleco UV–Visible Double
Spectrophotometer at 517 nm. While assigning spectral data sev-
eral abbreviations were used and these include ‘Ar’ for aromatic,
‘Ace’ for acetal, ‘Sac’ for saccharide, ‘Py’ for pyridopyrimidine moi-
ety, ‘Pyr’ for pyrrole and ‘Ha & Hb’ for the diasteretopic protons
present in the methylene linker. Alk-Ha and Alk-Hb represent the
alkenic protons of sugar chalcones.
t
(cmÀ1): 3402.18, 2962.44, 2869.87, 2360.70, 1720.38, 1627.80.
Anal. Calcd for C21H28O6: C, 67.00; H, 7.50. Found: C, 66.94; H, 7.57.
4.2.3. Physicochemical and spectral data for (E)-1-(4,6-O-
butylidene-b-
D
-glucopyranosyl)-4-(4-chlorophenyl)but-3-en-2-
one (7f)
The reaction of (4,6-O-butylidene-b-
D
-glucopyranosyl)propan-
2-one (5) (1 mmol, 0.274 g) with p-chlorobenzaldehyde (6f)
(1.2 mmol, 0.168 g) in the presence of organo-catalyst such as pyr-
rolidine (30 mol %) using DCM as a solvent afforded the compound,
7f in 90% yield. Mp: 186–191 °C; 1H NMR (300 MHz, CDCl3 + DMSO-
d6, ppm): d 7.83–7.79 (m, 3H, Ar-H, Alk-Hb), 7.69–7.66 (d, 2H,
J = 8.1 Hz, Ar-H), 7.05 (d, 1H, J = 16.2 Hz, Alk-Ha), 5.29 (br, 1H, Sac-
OH), 5.04 (br, 1H, Sac-OH), 4.83 (t, 1H, J = 5.1 Hz, Ace-H), 4.39–4.35

44
M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
(dd, 1H, J = 3.9 Hz, J = 10.2 Hz, Sac-H), 4.22–4.15 (dt, 1H J = 2.4 Hz,
J = 9 Hz, Ano-H), 3.93 (t, J = 8.7 Hz, 1H, Sac-H), 3.73–3.67 (m, 1H,
Sac-H), 3.64–3.41 (m, 5H, Sac-H), 3.17–3.09 (dd, 1H, J = 8.7 Hz,
J = 15.9 Hz, CH2, Ha), 1.96–1.88 (m, 2H, CH2), 1.72 (q, 2H, J = 7.2 Hz,
CH2), 1.20 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (75 MHz,
CDCl3 + DMSO-d6, ppm): d 202.60 (CO), 146.18 (Alk-CH), 140.89
(Ar-C), 137.82 (Ar-C), 134.30 (Ar-CH), 133.90 (Alk-CH,), 131.70
(Alk-CH), 106.98 (Ace-CH), 85.37 (Sac-CH), 81.40 (Sac-CH), 79.65
(Sac-CH), 79.39 (Sac-CH), 75.36 (Sac-CH), 73.05 (Sac-CH2), 48.24
ethanol and then the freshly prepared sodium ethoxide (1–
3 mmol) solution was added slowly. Finally (E)-1-(4,6-O-butyli-
dene-b-
D-glucopyranosyl)-4-phenylbut-3-en-2-one
derivatives
(1 mmol) were dissolved portion wise and the mixture was al-
lowed to stir at room temperature for 30–90 min. The course of
the reaction was monitored through thin layer chromatography.
After the completion of the reaction the solvent was evaporated
under reduced pressure and excess of sodium ethoxide was neu-
tralized with 10% of HCl. Then the reaction mixture was washed
with saturated NaHCO3 solution and extracted with chloroform.
The extracted organic layer was dried with anhydrous Na2SO4
and concentrated to give a crude product which was further puri-
fied with the help of column chromatography.
(CH2), 41.00 (CH2), 22.14 (CH2), 18.69 (CH3). IR
2962.44, 2869.87, 2360.70, 1743.52, 1627.80. Anal. Calcd for
21H25ClO6: C, 60.53; H, 6.35. Found: C, 60.44; H, 6.28.
t
(cmÀ1): 3417.61,
C
4.2.4. Physicochemical and spectral data for (E)-1-(4,6-O-
butylidene-b-
D
-glucopyranosyl)-4-(3-bromo)phenylbut-3-en-2-
4.3.1. Physicochemical and spectral data for 7-(4,6-O-
one (7h)
butylidene-b-D-glucopyranosyl-1-methyl)-1,3-dimethyl-5-
The reaction of (4,6-O-butylidene-b-
D
-glucopyranosyl)propan-
phenylpyrido(2,3-d)pyrimidine-2,4(1H,3H)-dione (9a)
2-one (5) (1 mmol, 0.274 g) with m-bromobenzaldehyde (6h)
(1.2 mmol, 0.222 g) in the presence of organo-catalyst such as pyr-
rolidine (30 mol %) using DCM as a solvent afforded the compound,
7h in 85% yield. Mp: 180–185 °C; 1H NMR (300 MHz,
CDCl3 + DMSO-d6, ppm): d 7.64–7.56 (m, 4H, Ar-H, Alk-Hb), 7.40
(t, 1H, J = 7.8 Hz, Ar-H), 6.87 (d, 1H, J = 16.2 Hz, Alk-Ha), 4.65 (t,
1H, J = 4.5 Hz, Ace-H), 4.22–4.17 (m, 1H, Sac-H), 4.04–3.98 (m,
1H, Ano-H), 3.76 (t, 1H, J = 8.4 Hz, Sac-H), 3.55–3.24 (m, 4H, Sac-
H), 2.98–2.90 (dd, 2H, J = 8.4 Hz, J = 15 Hz, CH2, Ha), 1.77–1.73 (m,
2H, CH2), 1.55 (q, 2H, J = 7.2 Hz, CH2), 1.02 (t, 3H, J = 7.2 Hz, CH3).
13C NMR (75 MHz, CDCl3 + DMSO-d6, ppm): d 192.75 (CO), 135.68
(Ar-C), 131.33 (Alk-CH), 127.77 (Ar-CH), 125.48 (Ar-CH), 125.17
(Ar-CH), 122.29 (Ar-CH,), 121.61 (Alk-CH), 117.57 (Ar-C), 96.91
(Ace-CH), 75.19 (Sac-CH), 71.19 (Sac-CH), 69.69 (Sac-CH), 69.39
(Sac-CH), 65.28 (Sac-CH), 62.97 (Sac-CH2), 38.28 (CH2), 30.92
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-phe-
nylbut-3-en-2-one (7a) (1 mmol, 0.362 g) in the presence of so-
dium ethoxide (1 mmol, 0.068 g) as a base at room temperature
for 30 min afforded a white solid of compound, 9a in 73% yield.
Mp: 174–178 °C; 1H NMR (300 MHz, CDCl3, ppm): d 7.45–7.43
(m, 3H, Ar-H), 7.29–7.28 (m, 2H, Ar-H), 6.92 (s, 1H, Py-H), 4.52 (t,
1H, J = 5.1 Hz, Ace-H), 4.08–4.03 (dd, 1H, J = 3.9 Hz, J = 10.2 Hz,
Sac-H), 3.92–3.86 (dt, 1H, J = 3.3 Hz, J = 9 Hz, Ano-H), 3.76 (s, 3H,
NCH3, Sac-H), 3.48–3.41 (m, 4H, Sac-H), 3.36 (m, 3H, NCH3, Sac-
H), 3.31–3.23 (m, 2H, Sac-H), 3.04 2.96 (dd, 1H, J = 7.8 Hz,
J = 14.7 Hz, CH2, Ha), 1.66–1.59 (m, 2H, CH2), 1.41 (q, 2H,
J = 7.5 Hz, CH2), 0.91 (t, 3H, J = 7.5 Hz, CH3). 13C NMR (75 MHz,
CDCl3, ppm): d 162.16 (Py-CO), 160.48 (Py-C), 154.67 (Py-C),
151.53 (Py-C), 151.41 (Py-CO) 139.17 (Ar-C), 128.20 (Ar-CH),
127.80 (Ar-CH, 3C), 122.68 (Py-CH), 106.37 (Py-C), 102.49 (Ace-
CH), 80.56 (Sac-CH), 78.56 (Sac-CH), 75.17 (Sac-CH), 74.41 (Sac-
CH), 70.74 (Sac-CH), 68.29 (Sac-CH2), 40.94 (CH2), 36.22 (CH2),
(CH2), 12.06 (CH2), 8.59 (CH3). IR
2869.87, 2360.70, 1743.52, 1627.80. Anal. Calcd for C21H25BrO7:
C, 54.43; H, 5.71. Found: C, 54.34; H, 5.76.
t
(cmÀ1): 3409.90, 2962.44,
30.20 (NCH3), 28.46 (NCH3), 17.45 (CH2), 13.91 (CH3). IR t
(cmÀ1):
4.2.5. Physicochemical and spectral data for (E)-1-(4,6-O-
3517.90, 3417.61, 2964.44, 2869.87, 2360.70, 1697.23, 1658.66,
1589.23, 1558.37. Anal. Calcd for C26H31N3O7: C, 62.76; H, 6.28;
N, 8.45. Found: C, 62.67; H, 6.22; N, 8.56.
butylidene-b-
D
-glucopyranosyl)-4-pyrrolobut-3-en-2-one (7i)
-glucopyranosyl)propan-
The reaction of (4,6-O-butylidene-b-
D
2-one (5) (1 mmol, 0.274 g) with pyrrole-2-carboxaldehyde (6i)
(1.2 mmol, 0.114 g) in the presence of organo-catalyst such as pyr-
rolidine (30 mol %) using DCM as a solvent afforded the compound,
7i in 85% yield. Mp: 192–196 °C; 1H NMR (300 MHz,
CDCl3 + DMSO-d6, ppm): d 11.45 (br, 1H, Pyr-NH), 7.80 (d, 1H,
J = 16.2 Hz, Alk-Hb), 7.30 (br, 1H, Pyr-H), 6.93–6.88 (m, 2H, Pyr-H,
Alk-Ha), 6.59 (br, 1H, Pyr-H), 5.27 (br, 1H, Sac-OH), 5.03 (br, 1H,
Sac-OH), 4.89 (t, 1H, J = 5.1 Hz, Ace-H), 4.45–4.41 (dd, 1H,
J = 3.9 Hz, J = 9.9 Hz, Sac-H), 4.27–4.21 (dt, 1H, J = 2.4 Hz,
J = 9.3 Hz, Ano-H), 3.97 (t, 1H, J = 8.7 Hz, Sac-H), 3.79–3.72 (m,
2H, Sac-H), 3.66–3.52 (m, 6H, Sac-H), 3.10–3.07 (dd, 2H,
J = 8.7 Hz, J = 15 Hz, CH2, Ha), 2.02–1.91 (m, 2H, CH2), 1.78 (q, 2H,
J = 7.2 Hz, CH2), 1.27 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (75 MHz,
CDCl3 + DMSO-d6,): d 202.67 (CO), 147.58 (Alk-CH), 139.23 (Pyr-
C), 135.25 (Alk-CH), 133.71 (Pyr-CH), 133.05 (Pyr-CH), 131.34
(Pyr-CH), 106.93 (Ace-CH), 85.47 (Sac-CH), 81.51 (Sac-CH), 79.67
(Sac-CH), 79.44 (Sac-CH), 75.40 (Sac-CH), 73.06 (Sac-CH2), 48.19
4.3.2. Physicochemical and spectral data for 7-(4,6-O-butyli
dene-b-D-glucopyranosyl-1-methyl)-5-(4-methoxyphenyl)-1,3-
dimethylpyrido(2,3-d)pyrimidine-2,4(1H,3H)-dione (9b)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-(4-
methoxyphenyl)but-3-en-2-one (7b) (1 mmol, 0.392 g) in the
presence of sodium ethoxide (1 mmol, 0.068 g) as a base at room
temperature for 35 min afforded light yellowish a white solid of
compound 9b in 82% yield. Mp: 175–179 °C; 1H NMR (300 MHz,
CDCl3, ppm): d 7.17 (d, 2H, J = 8.4 Hz, Ar-H), 6.88 (d, 2H, J = 8.7,
Ar-H), 6.83 (s, 1H, Py-H), 4.46 (t, 1H, J = 4.8 Hz, Ace-H), 4.24 (br,
1H, Sac-H), 3.97–3.94 (m, 2H, Sac-H, Ano-H), 3.81–3.78 (m, 4H,
NCH3, Sac-H), 3.68 (s, 3H, Ar-OCH3), 3.37–3.33 (m, 3H, Sac-H),
3.30 (s, 3H, NCH3), 3.19–3.18 (m, 2H, Sac-H), 2.88–2.80 (dd, 1H,
J = 8.7 Hz, J = 14.7 Hz, CH2, Ha), 1.57–1.54 (m, 2H, CH2), 1.34 (q,
2H, J = 7.2 Hz, CH2), 0.83 (t, 3H, J = 7.2 Hz, CH3). 13C NMR
(75 MHz, CDCl3, ppm): d 162.52 (Py-CO), 160.69 (Py-C), 159.63
(Ar-C), 154.14 (Py-C), 151.56 (Py-C), 151.45 (Py-CO), 131.30 (Ar-
C), 129.50 (Ar-CH), 122.79 (Py-CH), 113.19 (Ar-CH), 106.11
(Py-C), 102.39 (Ace-CH), 80.49 (Sac-CH), 78.81 (Sac-CH), 75.16
(Sac-CH), 74.74 (Sac-CH), 70.67 (Sac-CH), 68.33 (Sac-CH2), 55.24
(Ar-OCH3), 40.82 (CH2), 36.25 (CH2), 30.15 (NCH3), 28.41 (NCH3),
(CH2), 41.03 (CH2), 22.12 (CH2), 18.72 (CH3). IR t
(cmÀ1): 3355.89,
2962.44, 2869.87, 1681.80, 1581.51. Anal. Calcd for C18H25NO6: C,
61.52; H, 7.17; N, 3.99. Found: C, 61.44; H, 7.25, N, 4.10.
4.3. General procedure for the reaction of (E)-1-(4,6-O-
butylidene-b-D-glucopyranosyl)-4-phenylbut-3-en-2-one
derivatives with 6-amino-1,3-dimethyluracil
17.43 (CH2), 13.91 (CH3). IR t
(cmÀ1): 3494.76, 3448.47, 2962.44,
2869.87, 2360.70, 1704.95, 1658.66, 1589.23, 1550.65. Anal. Calcd
for C27H33N3O8: C, 61.47; H, 6.30; N, 7.96. Found: C, 61.37; H, 6.35;
N, 7.86.
6-Amino-1,3-dimethyluracil (1.2 mmol) was added in the sol-
vent mixture containing 15 mL of dry THF and 5 mL of absolute

M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
45
4.3.3. Physicochemical and spectral data for 7-(4,6-O-
butylidene-b- -glucopyranosyl-1-methyl)-5-(4-methylphenyl)-
1,3-dimethylpyrido(2,3-d)pyrimidine-2,4(1H,3H)-dione (9c)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
H), 3.86 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 3.70–3.65 (m, 4H,
NCH3, Sac-H), 3.42–3.34 (m, 3H, Sac-H), 3.31(s, 3H, -NCH3), 3.27–
3.13 (m, 3H, Sac-H), 2.97–2.89 (dd, 1H, J = 7.4 Hz, J = 14.7 Hz, CH2,
Ha), 1.59–1.52 (m, 2H,CH2), 1.35 (q, 2H, J = 7.5 Hz, CH2), 0.84 (t,
3H, J = 7.5 Hz, CH3). 13C NMR (75 MHz, CDCl3, ppm): d 161.97
(Py-CO), 160.43 (Py-C), 154.52 (Py-C), 151.63 (Py-C), 151.41 (Py-
CO) 149.23 (Ar-C), 148.30 (Ar-C), 131.53 (Ar-C), 122.86 (Py-CH),
120.72 (Ar-CH), 111.83 (Ar-CH), 110.51 (Ar-CH), 106.39 (Py-C),
102.49 (Ace-CH), 80.51 (Sac-CH), 78.56 (Sac-CH), 75.18 (Sac-CH),
74.46 (Sac-CH), 70.71 (Sac-CH), 68.29 (Sac-CH2), 56.00 (Ar-OCH3),
55.87 (Ar-OCH3), 40.94 (CH2), 36.22 (CH2), 30.21 (NCH3), 28.48
D
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-(4-
methylphenyl)but-3-en-2-one (7c) (1 mmol, 0.376 g) in the
presence of sodium ethoxide (1 mmol, 0.068 g) as a base at room
temperature for 30 min afforded a white solid of compound 9c in
81% yield. Mp: 198–203 °C; 1H NMR (300 MHz, CDCl3, ppm): d
7.25 (d, 2H, J = 9.6 Hz, Aro-H), 7.18 (d, 2H, J = 8.1 Hz, Ar-H), 6.91
(s, 1H, Py-H), 4.52 (t. 1H, J = 5.1 Hz, Ace-H), 4.08–4.03 (dd, 1H,
J = 3.6 Hz, J = 10.2 Hz, Sac-H), 3.92–3.85 (dt, 1H, J = 3.3 Hz,
J = 8.4 Hz, Ano-H), 3.75 (s, 3H, NCH3), 3.48–3.41 (m, 3H, Sac-H),
3.37 (s, 3H, NCH3), 3.31–3.20 (m, 3H, Sac-H), 3.04–2.97 (dd, 1H,
J = 7.5 Hz, J = 14.7 Hz, CH2, Ha), 2.42 (s,3H, -CH3), 1.66–1.59 (m,
2H, CH2), 1.41 (q, 2H, J = 7.5 Hz, CH2), 0.91 (t, 3H, J = 7.5 Hz, CH3).
13C NMR (75 MHz, CDCl3, ppm): d 162.02 (Py-CO), 160.52 (Py-C),
154.85 (Py-C), 151.55 (Py-C), 151.42 (Py-CO), 138.18 (Ar-C),
136.14 (Ar-C), 128.54 (Aro-CH), 127.81 (Ar-CH), 122.78 (Py-CH),
106.41 (Py-C), 102.47 (Ace-CH), 80.50 (Sac-CH), 78.56 (Sac-CH),
75.14 (Sac-CH), 74.41 (Sac-CH), 70.71 (Sac-CH), 68.29 (Sac-CH2),
40.93 (CH2), 36.22 (CH2), 30.19 (NCH3), 28.46 (NCH3), 21.38 (Ar-
(NCH3), 17.44 (CH2), 13.90 (CH3). IR t
(cmÀ1): 3571.90, 3463.90,
2962.44, 2869.87, 2360.70, 1712.66, 1666.37, 1589.23, 1550.65.
Anal. Calcd for C28H35N3O9: C, 60.31; H, 6.33; N, 7.54. Found: C,
60.41; H, 6.40; N, 7.44.
4.3.6. Physicochemical and spectral data for 5-(4-
chlorophenyl)-7-(4,6-O-butylidene-b-D-glucopyranosyl-1-
methyl)-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-
dione (9f)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-
CH3), 17.45 (CH2), 13.91 (CH3). IR
t
(cmÀ1): 3517.90, 3417.61,
(4-chlorophenyl)-but-3-en-2-one (7f) (1 mmol, 0.396 g) in the
presence of sodium ethoxide (3 mmol, 0.276 g) as a base at room
temperature for 30 min afforded a white solid of compound 9f in
83% yield. Mp: 209–214 °C; 1H NMR (300 MHz, CDCl3, ppm): d
7.34 (d, 2H, J = 8.4 Hz, Ar-H), 7.15 (d, 2H, J = 8.4 Hz, Ar-H), 6.81 (s,
1H, Py-H), 4.45 (t. 1H, J = 4.8 Hz, Ace-H), 4.00–3.95 (dd, 1H,
J = 3.6 Hz, J = 9.9 Hz, Sac-H), 3.82 (dt, 1H, J = 3 Hz, J = 7.5 Hz, Ano-
H), 3.69–3.65 (m, 4H, NCH3, Sac-H), 3.41–3.33 (m, 3H, Sac-H),
3.29 (s, 3H, NCH3), 3.27–3.12 (m, 2H, Sac-H), 2.97–2.89 (dd, 1H,
J = 8.1 Hz, J = 14.7 Hz, CH2, Ha), 1.57–1.52 (m, 2H, CH2), 1.34 (q,
2H, J = 7.5 Hz, CH2), 0.84 (t, 3H, J = 7.5 Hz, CH3), 13C NMR
(75 MHz, CDCl3, ppm): d 162.47 (Py-CO), 160.50 (Py-C), 153.33
(Py-C), 151.60 (Py-C), 151.30 (Py-CO), 137.51 (Ar-C), 134.41 (Ar-
C), 129.26 (Ar-CH), 128.07 (Ar-CH), 122.46 (Py-CH), 106.22 (Py-
C), 102.50 (Ace-CH), 80.48 (Sac-CH), 78.53 (Sac-CH), 75.20 (Sac-
CH), 74.35 (Sac-CH), 70.71 (Sac-CH), 68.27 (Sac-CH2), 40.91 (CH2),
36.21 (CH2), 30.21 (NCH3), 28.46 (NCH3), 17.44 (CH2), 13.90
2962.44, 2969.87, 2360.70, 1697.23, 1658.66, 1589.23, 1550.65.
Anal. Calcd for C27H33N3O7: C, 63.39; H, 6.50; N, 8.21. Found: C,
63.45; H, 6.42; N, 8.16.
4.3.4. Physicochemical and spectral data for 5-(benzo[d]dioxol-
5-yl)-7-(4,6-O-butylidene-b-D-glucopyranosyl–1-methyl)-1,3-
dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (9d)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-(3,
4-dioxanephenyl)-but-3-en-2-one (7d) (1 mmol, 0.402 g) in the
presence of sodium ethoxide (1 mmol, 0.068 g) as a base at room
temperature for 60 min afforded a light yellowish solid of com-
pound 9d in 72% yield. Mp: 132–137 °C; 1H NMR (300 MHz, CDCl3,
ppm): d 6.83 (s, 1H, Py-H), 6.79 (s, 1H, Ar-H), 6.69–6.68 (m, 2H, Ar-
H), 5.95 (s, 2H, OCH2O), 4.45 (t. 1H, J = 5.1 Hz, Ace-H), 4.00–3.96
(dd, 1H, J = 3.9 Hz, J = 9.6 Hz, Sac-H), 3.78–3.84 (dt, 1H, J = 3.9 Hz,
J = 7.2 Hz, Ano-H), 3.70–3.65 (m, 4H, NCH3, Sac-H), 3.40–3.33 (m,
1H, Sac-H), 3.30 (s, 3H, NCH3), 3.29–3.15 (m, 3H, Sac-H), 2.95–
2.88 (dd, 1H, J = 7.8 Hz, J = 14.7 Hz, CH2, Ha), 1.59–1.52 (m, 2H,
CH2), 1.34 (q, 2H, J = 7.2 Hz, CH2), 0.84 (t, 3H, J = 7.2 Hz, CH3). 13C
NMR (75 MHz, CDCl3, ppm,): d 162.14 (Py-CO), 160.44 (Py-C),
154.26 (Py-C), 151.60 (Py-C), 151.37 (Py-CO), 147.78 (Ar-C),
147.15 (Ar-C), 132.77 (Ar-C), 122.77 (Py-CH), 121.55 (Ar-CH),
109.02 (Ar-CH), 107.90 (Ar-CH), 106.41 (Py-C), 102.49 (Ace-CH),
101.29 (OCH2O), 80.52 (Sac-CH), 78.59 (Sac-CH), 75.18 (Sac-CH),
74.41 (Sac-CH), 70.71 (Sac-CH), 68.29 (Sac-CH2), 40.90 (CH2),
36.22 (CH2), 30.19 (NCH3), 28.46 (NCH3), 17.44 (CH2), 13.88
(CH3). IR t
(cmÀ1): 3517.90, 3433.04, 2970.16, 2869.87, 2360.87,
1704.95, 1658.66, 1589.23, 1550.65. Anal. Calcd for C26H30ClN3O7:
C, 58.70; H, 5.68; N, 7.90. Found: C, 58.61; H, 5.73; N, 8.00.
4.3.7. Physicochemical and spectral data for 5-(4-fluorophenyl)-
7-(4,6-O-butylidene-b-D-glucopyranosyl-1-methyl)-1,3-
dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (9g)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-(4-
fluorophenyl)-but-3-en-2-one (7g) (1 mmol, 0.381 g) in the
presence of sodium ethoxide (3 mmol, 0.276 g) as a base at room
temperature for 30 min afforded a light yellowish solid of com-
pound 9g in 82% yield. Mp: 189–194 °C; 1H NMR (300 MHz, CDCl3,
ppm): d 7.26–7.23 (m, 2H, Ar-H), 7.15–7.09 (m, 2H, Ar-H), 6.89 (s,
1H, Py-H), 4.52 (t. 1H, J = 4.8 Hz, Ace-H), 4.07–4.02 (dd, 1H,
J = 3.6 Hz, J = 10.2 Hz, Sac-H), 3.93–3.86 (dt, 1H, J = 3.3 Hz,
J = 9 Hz, Ano-H), 3.76–3.71 (m, 4H, NCH3, Sac-H), 3.48–3.41 (m,
2H, Sac-H), 3.37 (s, 3H, NCH3), 3.34–3.23 (m, 3H, Sac-H), 3.03–
2.96 (dd, 1H, J = 8.1 Hz, J = 15 Hz, CH2, Ha),1.66–1.59 (m, 2H, CH2),
1.41 (q, 2H, J = 7.2 Hz, CH2), 0.91 (t, 3H, J = 7.2 Hz, CH3). 13C NMR
(75 MHz, CDCl3, ppm): d 162.37 (Py-CO), 160.54 (Py-C), 153.59
(Py-C), 151.60 (Py-C), 151.31 (Py-CO), 134.97 (Ar-C), 134.92
(Ar-C), 129.80 (Ar-CH), 129.69 (Ar-CH), 122.68 (Py-CH), 115.03
(Ar-CH), 114.74 (Ar-CH), 106.32 (Py-C), 102.50 (Ace-CH), 80.50
(Sac-CH), 78.56 (Sac-CH), 75.19 (Sac-CH), 74.38 (Sac-CH), 70.70
(Sac-CH), 68.27 (Sac-CH2), 40.90 (CH2), 36.21 (CH2), 30.21 (NCH3),
(CH3). IR t
(cmÀ1): 3510.19, 3394.47, 2962.44, 2877.58, 2360.70,
1704.95, 1658.66, 1589.23, 1558.37. Anal. Calcd for C27H33N3O9:
C, 59.88; H, 5.77; N, 7.76. Found: C, 59.80; H, 5.71; N, 7.66.
4.3.5. Physicochemical and spectral data for 7-(4,6-O-
butylidene-b-D-glucopyranosyl-1-methyl)-5-(3,4-
dimethoxyphenyl)-1,3-dimethylpyrido[2,3-d]pyrimidine-
2,4(1H,3H)-dione (9e)
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-(3,4-
dimethoxyphenyl)-but-3-en-2-one (7e) (1 mmol, 0.422 g) in the
presence of sodium ethoxide (2 mmol, 0.136 g) as a base at room
temperature for 65 min afforded a light yellowish solid of com-
pound 9e in 79% yield. Mp: 80–85 °C; 1H NMR (300 MHz, CDCl3,
ppm): d 6.78–6.78 (m, 3H, Ar-H), 6.75 (s, 1H, Py-H), 4.45 (t. 1H,
J = 5.1 Hz, Ace-H), 4.00–3.96 (dd, 1H, J = 3.6 Hz, J = 10.2 Hz, Sac-
28.46 (NCH3), 17.44 (CH2), 13.90 (CH3). IR
t
(cmÀ1): 3517.90,

46
M. J. Shanmugam, T. Mohan Das / Carbohydrate Research 368 (2013) 40–46
3433.04, 2970.16, 2869.87, 2360.70, 1704.95, 1658.66, 1596.94,
1558.37. Anal. Calcd for C26H30FN3O7: C, 60.57; H, 5.87; N, 8.15.
Found: C, 60.50; H, 5.80; N, 8.21.
for C24H30N4O7: C, 59.25; H, 6.22; N, 11.52. Found: C, 59.17; H,
6.27; N, 7.43.
Acknowledgment
4.3.8. Physicochemical and spectral data for 5-(3-
bromophenyl)-7-(4,6-O-butylidene-b-
methyl)-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-
dione (9h)
D
-glucopyranosyl-1-
Authors acknowledge SERC-DST, New Delhi, India for financial
support and DST-FIST for NMR and FT-IR facilities in the Depart-
ment of Organic Chemistry, University of Madras, Chennai, India.
M. J. S. thanks SERC-DST, New Delhi for research fellowship.
The reaction of 6-amino-1,3-dimethyluracil (8) (1.2 mmol,
0.186 g) with (E)-1-(4,6-O-butylidene-b-D-glucopyranosyl)-4-
(3-bromophenyl)-but-3-en-2-one (7h) (1 mmol, 0.441 g) in the
presence of sodium ethoxide (3 mmol, 0.276 g) as a base at room
temperature for 90 min afforded a yellowish solid of compound
9h in 67% yield. Mp: 72–76 °C; 1H NMR (300 MHz, CDCl3, ppm):
d 7.55 (d, 1H, J = 7.8 Hz, Ar-H). 7.42 (s, 1H, Ar-H), 7.33–7.23 (m,
2H, Ar-H), 6.88 (s, 1H, Py-H), 4.53 (t, 1H, J = 5.1 Hz, Ace-H), 4.08–
4.03 (dd, 1H, J = 3.9 Hz, J = 10.2 Hz, Sac-H), 3.93–3.86 (dt, 1H,
J = 3 Hz, J = 8.7 Hz, Ano-H), 3.76–3.72 (m, 4H, NCH3, Sac-H), 3.48–
3.41 (m, 2H, Sac-H), 3.40–3.36 (s, 4H, NCH3, Sac-H), 3.28–3.23
(m, 2H, Sac-H), 3.03–2.95 (dd, 1H, J = 8.1 Hz, J = 14.7 Hz, CH2, Ha),
1.66–1.59 (m, 2H, CH2), 1.41 (q, 2H, J = 7.2 Hz, CH2), 0.91 (t, 3H,
J = 7.2 Hz, CH3). 13C NMR (75 MHz, CDCl3, ppm): d 162.60 (Py-
CO), 160.36 (Py-C), 152.73 (Py-C), 151.52 (Py-C), 151.32 (Py-CO),
141.11 (Ar-C), 131.15 (Ar-CH), 130.59 (Ar-CH), 129.22 (Ar-CH),
126.69 (Ar-CH), 122.40 (Py-CH), 121.86 (Ar-C), 106.18 (Py-C),
102.49 (Ace-CH), 80.48 (Sac-CH), 78.55 (Sac-CH), 75.20 (Sac-CH),
74.35 (Sac-CH), 70.70 (Sac-CH), 68.27 (Sac-CH2), 40.91 (CH2),
36.21 (CH2), 30.21 (NCH3), 28.49 (NCH3), 17.44 (CH2), 13.91
Supplementary data
Supplementary data (copy of all the spectra, optimization of
reaction conditions) associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2012.11.
013.
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butylidene-b-D-glucopyranosyl-1-methyl)-1,3-dimethylpyrido-
5-(1H-pyrrol-2yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (9i)
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pyrrol-2yl)-but-3-en-2-one (7i) (1 mmol, 0.351 g) in the presence
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CH2), 1.56(q, 2H, J = 7.2 Hz, CH2), 1.05 (t, 3H, J = 7.2 Hz, CH3). 13C
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(Sac-CH2), 45.49 (CH2), 41.04 (CH2), 35.32 (NCH3), 33.76 (NCH3),
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22.12 (CH2), 18.74 (CH3). IR
2877.58, 2360.70, 1689.52, 1627.80, 1596.94, 1535.22. Anal. Calcd
t
(cmÀ1): 3456.18, 3132.17, 2962.44,