Synthesis of novel galactopyranosyl-derived spiro barbiturates

Article abstract of DOI:10.1080/07328300601039328

Malonic acid undergoes condensation readily with ureas to yield barbituric acids 2, which on bromination give 5,5-dibromobarbituric acids 3. Reaction of α-D-galactose with these 5,5-dibromo barbituric acids afforded 2,3-α-D-galactopyrano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,10-triones 4. The structures of the products have been assigned on the basis of ¹H NMR, ¹³C NMR, FAB-MS, optical activity, and elemental analysis. The title compounds are found to have antibacterial and antifungal activities.

Full text of DOI:10.1080/07328300601039328

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Synthesis of Novel Galactopyranosyl‐Derived
Spiro Barbiturates
V. N. Ingle a , P. K. Gaidhane a , S. S. Dutta a , P. P. Naha a & M. S. Sengupta a
a Department of Chemistry, Rashtrasant Tukdoji Maharaj Nagpur University,
Nagpur, India
Version of record first published: 02 Feb 2007
To cite this article: V. N. Ingle, P. K. Gaidhane, S. S. Dutta, P. P. Naha & M. S. Sengupta (2006): Synthesis of
Novel Galactopyranosyl‐Derived Spiro Barbiturates, Journal of Carbohydrate Chemistry, 25:8-9, 661-671
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Journal of Carbohydrate Chemistry, 25:661–671, 2006
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300601039328
Synthesis of Novel
Galactopyranosyl-Derived
Spiro Barbiturates
V. N. Ingle, P. K. Gaidhane, S. S. Dutta, P. P. Naha, and
M. S. Sengupta
Department of Chemistry, Rashtrasant Tukdoji Maharaj Nagpur University, Nagpur,
India
Malonic acid undergoes condensation readily with ureas to yield barbituric acids 2,
which on bromination give 5,5-dibromobarbituric acids 3. Reaction of a-D-galactose
with these 5,5-dibromo barbituric acids afforded 2,3-a-D-galactopyrano-1,4-dioxo-7,9-
diaza-spiro[4,5]deca-6,8,10-triones 4. The structures of the products have
been assigned on the basis of 1H NMR, 13C NMR, FAB-MS, optical activity, and elemen-
tal analysis. The title compounds are found to have antibacterial and antifungal
activities.
Keywords Barbituric acid, 5, 5-Dibromo barbituric acid, a-D-Galactose, Dioxolane,
Triones
INTRODUCTION
SPIRO systems have been the subject of considerable interest in chemistry
because of their unique structural and reactivity pattern. Many spiro com-
pounds possess antiparasitic and analgesic activities.[1] The literature
reports revealed the synthesis of spiroheterocycles, which were used as inter-
mediates for aldose reductase inhibitors, and some new spiroheterocycles
are also found to have activity as herbicides and pesticides.[2] Spirocarbocyclic
systems also enhance the biologic potency of certain compounds.[3] Barbituric
acids have been reported to possess a wide spectrum of biologic activities
as sedatives and hypnotics, antitumor, antiviral, anti-inflammatory,
Received September 9, 2006; accepted October 10, 2006.
Address correspondence to V. N. Ingle, Department of Chemistry, Rashtrasant Tukdoji
Maharaj Nagpur University, Nagpur 440033, India. E-mail: pravin.kg@rediffmail.com
661

V. N. Ingle et al.
662
antisclerotics, and bacteriostatics.[4–6] 1,3-Dioxolanes have been used as
antispasmodics,[7] sedatives, analgesics, tranquilizers and anesthesis.[8] Drugs
modified with carbohydrates exhibit a variety of biologic and therapeutic prop-
erties. Certain glycoconjugates are more readily excretable and resistant to
significant metabolic transformation.[9–12] In continuation of our work on
the synthesis of 2,3-a-D-glucopyrano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,
10-triones based on the interaction of a-D-glucopyranose and 5,5-dibromo
barbituric acid,[13] herein we report the synthesis and screening results of
2,3-a-D-galactopyrano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,10-triones
4 in
antibacterial and antifungal assays.
RESULTS AND DISCUSSION
The barbituric acids 2 were prepared by the Biltz and Wittek method[14] in
which ureas 1 are condensed with malonic acid in acetic acid-acetic anhy-
dride. 5,5-Dibromo barbituric acids 3 were prepared by adding bromine to bar-
bituric acids in suitable solvents.[15,16] Glacial acetic acid was found to be the
most convenient solvent for bromition of N-substituted barbituric acids. These
acids gave a positive test for bromine. The rate of dioxolane formation-ether-
ification depends on the presence of substituents attached to nitrogen atoms
in barbituric acids. It is fast in the case of 1-aryl and 1,3-diaryl barbituric
acids. The replacement of N-hydrogen by aryl groups increases the solubility
of barbituric acids in organic solvents. In the 1H NMR spectrum, 3a exhibited
a singlet for NH at d 11.68 ppm, while the 13C NMR spectrum showed peaks
at 163 (C-6, C-4,), 148 (C-2), and 46 ppm (C-5, C22Br). The IR spectrum
showed absorption bands at 3203 (NH), 1714 (C55O), 1183 (C-N-C), and
587 cm21 (C-Br). The reaction of 5,5-dibromo barbituric acid 3a with a-D-
galactose afforded 4a. The negative test for bromine, the absence of C-Br
absorption band in the spectrum, and the presence of strong band at
1263 cm21 for C-O-C is fully consistent with structure of 2,3-a-D-galactopyr-
ano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,10-triones 4a. The IR spectrum
showed characteristic bands at 3131 (OH), 3061 (NH), 2956 (galactosidic
1
CH), 1708 (C55O), 1176 (C-N-C), and 1152 cm21 (C-O) groups. The H NMR
spectrum of 4a showed signals at d 11.72 (s, 1H, N-H), 9.79, (s, 1H, O-H),
5.05–5.12 (m, H-20, anomeric proton), and 4.68 ppm (d, H-10, anomeric
13
proton). In the proton-decoupled C NMR, the anomeric carbon C-10 and
C-20 resonated at 102 and 82 ppm, respectively. The FAB-MS spectrum
showed a molecular ion peak at 304 (Mþ) and was dominated by m/z 126
(C4O3N2H2) with the loss of 178 amu corresponding to the loss of an intact
sugar moiety, C6H10O6. Also, the molecular ion peak at 304 (Mþ) confirms
the molecular formula C10O9N2H12. All the compounds gave satisfactory C,
H, and N elemental analysis (Table 2).

Table 1: Characterization data of compound 2a–2k.
%Found (Calcd)
H
Product
R
R1
Mol. Formula
mp (8C)
Yield (%)
C
N
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
C6H5
C6H5
H
H
C4H4O3N2
255
262
238
181
210
243
233
253
186
190
220
50
48
52
44
47
44
49
41
43
49
48
37.82 (37.50)
59.69 (59.40)
69.23 (69.06)
33.69 (33.41)
44.91 (44.62)
33.57 (33.41)
44.93 (44.62)
32.42 (32.11)
41.96 (41.86)
32.47 (32.11)
41.93 (41.86)
3.83 (3.12)
3.98 (3.96)
4.54 (4.31)
2.84 (2.53)
3.72 (3.30)
2.91 (2.53)
3.77 (3.30)
2.76 (2.43)
3.42 (3.10)
2.81 (2.43)
2.81 (3.10)
21.98 (21.87)
13.93 (13.86)
10.37 (10.07)
7.39 (7.08)
5.86 (5.78)
7.33 (7.08)
5.85 (5.78)
6.97 (6.81)
5.84 (5.42)
6.96 (6.81)
5.79 (5.42)
C10H8O3N2
C16H12O3N2
C11H10O3N2
C18H16O3N2
C11H10O3N2
C18H16O3N2
C11H10O4N2
C18H16O5N2
C11H10O4N2
C18H16O5N2
C6H5
H
O-CH3-C6H4
O-CH3-C6H4
O-CH3-C6H4
p-CH3-C6H4
p-CH3-C6H4
O-OCH3-C6H4
O-OCH3-C6H4
P-OCH3-C6H4
P-OCH3-C6H4
H
p-CH3-C6H4
H
O-OCH3-C6H4
H
P-OCH3-C6H4
2j
2k

Table 2: Characterization data of compounds 4a–4k.
% Found (Calcd)
H
Product
R
R1
Mol. Formula mp (8C) Yield (%) [a]2D9 (8)
C
N
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
C6H5
C6H5
H
H
C10H12O9N2
C10H12O9N2
C22H20O9N2
C17H17O9N2
C24H24O9N2
C17H17O9N2
C24H24O9N2
C17H18O10N2
.285
164
198
228
252
105
265
137
118
166
270
80
82
79
82
78
81
79
80
81
76
82
50.72 39.71 (39.47) 3.71 (3.94)
60.71 50.95 (50.52) 4.52 (4.21)
67.72 57.94 (57.89) 4.55 (4.38)
100.67 51.95 (51.64) 4.66 (4.56)
113.38 59.18 (59.50) 4.72 (4.95)
291.72 51.76 (51.64) 4.77 (4.56)
72.47 59.22 (59.50) 4.77 (4.95)
46.29 49.51 (49.75) 4.33 (4.14)
35.85 55.62 (55.81) 4.90 (4.65)
129.68 49.53 (49.75) 4.31 (4.14)
254.34 55.64 (55.81) 4.87 (4.65)
7.44 (7.36)
7.48 (7.36)
6.34 (6.14)
7.12 (7.08)
5.91 (5.78)
7.18 (7.08)
5.90 (5.78)
6.98 (6.82)
5.77 (5.42)
6.96 (6.82)
5.76 (5.42)
C6H5
H
O-CH3-C6H4
O-CH3-C6H4
O-CH3-C6H4
p-CH3-C6H4
p-CH3-C6H4
O-OCH3-C6H4
O-OCH3-C6H4 O-OCH3-C6H4 C24H24O11N2
P-OCH3-C6H4 C17H18O10N2
P-OCH3-C6H4 P-OCH3-C6H4 C24H24O11N2
H
p-CH3-C6H4
H
4j
4k
H

Galactopyranosyl-Derived Spiro Barbiturates
665
MICROBIAL ACTIVITY
Antimicrobial Activity
The synthesized compounds were screened for their antibacterial activities
by the using the cup-plate method against Bacillus subtilis (gram-positive) and
Escherichia coli (gram-negative) at concentrations of 100 mg/mL in DMF. Pure
norfloxacin was taken as standard antibiotic for the comparison of the results.
The sterilized nutrient agar media (30 mL) was inoculated with the test
organism and poured optically into the Petridishes. Then four holes of 6-mm
diameter were punched carefully by the using sterile cork-border and these
were completely filled with different test solution. The plates were then incu-
bated for 24 h at 378C and zones of inhibitions were measured. Similar pro-
cedure was adopted for pure norfloxacin and the corresponding zone
diameters were compared. The screening results indicate that compounds
4a–k showed moderate to excellent bactericidal activities against both organ-
isms (Table 3).
Table 3: Data for in vitro antibacterial and antifungal activities of
compounds 4a–k.
Diameter of Inhibition Zone (in mm) Against
Bacterial Strains
Fungal Strains
Products
E. coli
B. subtilis
A. niger
C. albicans
4a
4b
4c
4d
4e
4f
4g
4h
4i
15
14
10
12
16
13
14
11
15
13
14
17
16
09
10
14
13
16
14
13
11
16
21
17
11
15
24
17
22
16
23
—
22
23
15
—
13
28
—
18
16
21
17
22
4j
4k
— ¼ no inhibition of growth.
Diameter of zone of inhibition from 13–16 (in mm) shows excellent activity
and that of 9–12 (in mm) exhibits moderate activity for bacterial strains.
Diameter of zone of inhibition from 22–28 (in mm) shows excellent activity,
that of 15–21 (in mm) exhibits moderate activity, and that of 11–14 (in mm)
shows poor activity for fungal strains.
Norfloxacin 100 mg/mL used as standard against E. coli and B. subtilis;
diameter of zone of inhibition is 20.
Griseofulvin 100 mg/mL used as standard against A. niger and C. albicans;
diameter of zone of inhibition is 32.

V. N. Ingle et al.
666
Antifungal Activity
The antifungal activity of synthesized compounds was evaluated by the
using above same method (cup-plate technique) against Aspergillus niger
and Candida albicans at a concentration 100 mg/mL in DMF. The plates
were incubated for 8 days at 378C. The zones of inhibitions were measured.
Similarly, a commercial fungicide griseofulvin was also tested under similar
condition with a view of comparing the results. The compounds showed signifi-
cant fungitoxicity against both the test fungi (Table 3).
EXPERIMENTAL
General Methods
Substituted ureas 1 were prepared as described in the literature.[17]
Melting points were determined in open glass capillaries and are uncorrected.
Optical rotations were measured at 298C. Elemental analysis ware determined
using the Perkin Elmer 2400 CHN analyzer. FT-IR spectra were recorded using
1
(KBr) disc on Perkin-Elmer spectrum Rx-I spectrometer. H NMR and 13C
NMR were recorded on Brucker AC-300 F (300 MHz) NMR spectrometer by
using DMSO and CDCl3 as solvent and tetramethylsilane as an internal
standard. Mass spectra were recorded on 70-S Mass spectrometer using
m-nitro benzyl alcohol (NBA) matrix.
Barbituric acid 2a. Urea 1a (0.9 g, 0.015 mol) and malonic acid (2.08 g,
0.02 mol) are dissolved in 5 mL of glacial acetic acid in a flask fitted with
dropping funnel, reflux condenser, and stirrer. The mixture was heated to
658C and 4 mL of acetic anhydride was added during 30 min. The reaction
mixture was heated with stirring at 908C for 3 h. The solvent was removed
by distillation under vacuum at 608C and the residue was treated with 0.2 N
NaOH. The clear solution was acidified with 0.2 N HCl to obtain barbituric
acid 2a. mp 2558C (water) (yield 50%).
Similarly, 1-aryl and 1,3-diaryl barbituric acids (2b–k) were prepared by
the reaction of substituted ureas (1b–k) with malonic acid. Compounds gave
satisfactory C, H, and N analysis (Table 1).
5,5-Dibromobarbituric acid 3a. This was prepared by adding molecular
bromine (2.55 g, 0.016 mol) to barbituric acids 2a (1.28 g, 0.01 mol) in H2O
(60 mL) at 508C. mp 2358C (aq MeOH) (yield 70%); IR (KBr): 3203 (-NH),
1
1714 (C55O), 1183 (C-N-C), 587 (C-Br); H NMR (300 MHz, CDCl3 þ DMSO-
d6): 11.68 (s, N-H); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 163 (C-4, C-6),
(s, C55O), 148 (C-2) (s, C55O), 46 (C-5) (C-Br). Anal. Calcd. for C, 16.78; H,
0.69; N, 9.79. Found: C, 16.93; H, 1.03; N, 9.97%.
Similarly, 5,5-dibromo-1-aryl-and 1,3-diaryl barbituric acids (3b–k) were
prepared by adding bromine to 1-aryl and 1,3-diaryl barbituric acids (2b–k)
in suitable solvents.

Galactopyranosyl-Derived Spiro Barbiturates
667
5,5-Dibromo-1-phenyl barbituric acid 3b. mp 1848C (AcOH) (yield 68%);
IR (KBr): 3181 (-NH), 3056 (Ar-CH), 1731 (C55O), 1179 (C-N-C), 710 (Ar-H),
1
574 (C-Br); H NMR (300 MHz, CDCl3 þ DMSO-d6): 11.53 (s, 1H, N-H); 6.5–
9.1 (m, 5H, Ar-H); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 161 (C-4)
(s, C55O), 158 (C-6) (s, C55O), 150 (C-2) (s, C55O), 47 (C-5) (C-Br). Anal.
Calcd. for C, 33.14; H, 1.65; N, 7.73. Found: C, 33.54; H, 1.89; N, 7.93%.
5,5-Dibromo-1,3-diphenyl barbituric acid 3c. mp 1528C (benzene) (yield
71%); IR (KBr): 3071 (Ar-CH), 1720 (C55O), 1181 (C-N-C), 714 (Ar-H), 579
1
(C-Br); H NMR (300 MHz, CDCl3 þ DMSO-d6): 6.5–9.0 (m, 10H, Ar-H); 13C
NMR (100 MHz, CDCl3 þ DMSO-d6): 159 (C-4) (s, C55O), 157 (C-6) (s, C55O),
151 (C-2) (s, C55O), 46 (C-5) (C-Br). Anal. Calcd. for C, 43.83; H, 2.28; N,
6.69. Found: C, 43.97; H, 2.59; N, 6.74%.
5,5-Dibromo-1-o-tolyl barbituric acid 3d. mp 1748C (AcOH) (yield 69%); IR
(KBr): 3184 (-NH), 3049 (Ar-CH), 1733 (C55O), 1178 (C-N-C), 710 (Ar-H), 576
(C-Br); 1H NMR (300 MHz, CDCl3 þ DMSO-d6): 11.23 (s, 1H, N-H), 6.5–9.1
(m, 5H, Ar-H), 2.32 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 163
(C-4) (s, C55O), 156 (C-6) (s, C55O), 149 (C-2) (s, C55O), 49 (C-5) (C-Br), 21 (Ar-
CH3). Anal. Calcd. for C, 23.78; H, 1.44; N, 5.04. Found: C, 23.89; H, 1.79; N, 5.39%.
5,5-Dibromo-1,3-di-o-tolyl barbituric acid 3e. mp 1908C (ethanol) (yield
71%); IR (KBr): 3023 (Ar-CH), 1730 (C55O), 1175 (C-N-C), 715 (Ar-H), 580
1
(C-Br); H NMR (300 MHz, CDCl3 þ DMSO-d6): 6.5–9.0 (m, 10H, Ar-H), 2.29
(s, 6H, CH3); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 160 (C-4) (s, C55O),
159 (C-6) (s, C55O), 154 (C-2) (s, C55O), 46 (C-5) (C-Br), 19 (Ar-CH3). Anal.
Calcd. for C, 32.54; H, 2.17; N, 4.34. Found: C, 32.82; H, 2.41; N, 4.67%.
5,5-Dibromo-1-o-anisyl barbituric acid 3 h. mp 1818C (AcOH) (yield 74%);
IR (KBr): 3186 (-NH), 3059 (Ar-CH), 1747 (C55O), 1175 (C-N-C), 710 (Ar-H),
1
575 (C-Br); H NMR (300 MHz, CDCl3 þ DMSO-d6): 11.33 (s, 1H, N-H), 6.5–
9.0 (m, 5H, Ar-H), 3.79 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3 þ DMSO-
d6): 164 (C-4) (s, C55O), 157 (C-6) (s, C55O), 152 (C-2) (s, C55O), 59
(Ar-OCH3), 48 (C-5) (C-Br). Anal. Calcd. for C, 23.11; H, 1.40; N, 4.90. Found:
C, 23.37; H, 1.73; N, 4.98%.
5,5-Dibromo-1,3-di-o-anisyl barbituric acid 3i. mp 1648C (AcOH) (yield
72%); IR (KBr): 3063 (Ar-CH), 1734 (C55O), 1175 (C-N-C), 715 (Ar-H), 571
1
(C-Br); H NMR (300 MHz, CDCl3 þ DMSO-d6): 6.5–9.0 (m, 10H, Ar-H), 3.82
(s, 6H, OCH3); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 162 (C-4) (s, C55O),
154 (C-6) (s, C55O), 150 (C-2) (s, C55O), 57 (Ar-OCH3), 49 (C-5) (C-Br). Anal.
Calcd. for C, 31.95; H, 2.07; N, 4.14. Found: C, 31.99; H, 2.37; N, 4.34%.
2,3-a-D-Galactopyrano-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,10-triones
4a. A mixture of 5,5-dibromo barbituric acid 3a (2.85 g, 0.01 mol), a-D-galactose
(1.80 g, 0.01 mol), pyridine (0.79 g, 0.01 mol), and alcohol (25 mL) was

V. N. Ingle et al.
668
refluxed for 3 h. The excess of solvent was distilled off and the syrup poured
onto crushed ice to obtain 4a. mp .2858C (AcOH) (yield 80%); IR (KBr):
3131 (-OH), 3061 (-NH), 2956 (galactosidic-CH), 1708 (C55O), 1263 (C-O-C),
1176 (C-N-C), 1152 (C-O); 1H NMR (300 MHz, CDCl3 þ DMSO-d6): 11.72
(s, 1H, N-H); 9.79 (s, 1H, O-H), 5.5–5.3 (m, 2H, 30and 40-H); 5.05–5.12
(m,1H, 20-H, anomeric proton), 4.68 (d, 1H, 10-H, anomeric proton), 4.11 (dd,
2H, 60-H2), 3.77–3.82 (m, 1H, 50-H); 13C NMR (100 MHz, CDCl3 þ DMSO-d6):
165 (C-6) (s, C55O), 163 (C-4) (s, C55O), 148 (C-2) (s, C55O), 119 (C-5, spiro
C-atom), 102 (C-10, anomeric C-atom), 82 (C-20, anomerþic C-atom), 78 (C-50),
75 (C-30), 62 (C-40), 55 (C-60); FAB-MS: m/z 304 (M , C10O9N2H12), 126
(C4O3N2H2). Anal. Calcd. for C, 39.47; H, 3.94; N, 7.44. Found: C, 39.71; H,
3.72; N, 7.44%.
When the reaction of a-D-galactopyranose was extended with several other
5,5-dibromo- 1-aryl-and 1,3-diaryl barbituric acids (3b–k), then corresponding
2,3-a-D-galactopyrano-1,4-dioxo-7-aryl-7,9-diaza and 7,9-diaryl-7,9-diaza-
spiro[4,5]deca-6,8,10-triones (4b–k) have been synthesized.
2,3-a-D-Galactopyrano-7-phenyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,
10-triones 4b. IR (KBr): 3178 (-NH), 3201 (-OH), 3052 (Ar-CH), 2861 (galacto-
sidic-CH), 1728 (C55O), 1268 (C-O-C), 1172 (C-N-C), 1158 (C-O), 710 (Ar-H); 1H
NMR (300 MHz, CDCl3 þ DMSO-d6): 11.31 (s, N-H), 9.81 (s, O-H), 6.5–8.5
(m, 5H, Ar-H), 5.5–5.2 (m, 2H, 30and 40-H), 5.03–5.11 (m,1H, 20-H, anomeric
proton), 4.62 (d, 1H, 10-H, anomeric proton), 4.09 (dd, 2H, 60-H2), 3.76–3.84
(m, 1H, 50-H); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 162 (C-4) (s, C55O),
160 (C-6) (s, C55O), 154 (C-2) (s, C55O), 120–160 (aromatic C-atom), 118 (C-
5, spiro C-atom), 103 (C-10, anomeric C-atom), 85 (C-20, anomeric C-atom), 77
(C-50), 75 (C-30), 64 (C-40), 57 (C-60); FAB-MS: m/z 380 (Mþ, C16O9N2H16), 202
(C10O3N2H6), 125 (C4O3N2H).
2,3-a-D-Galactopyrano-7,9-diphenyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-
6,8,10-triones 4c. IR (KBr): 3244 (-OH), 3048 (Ar-CH), 2912 (galactosidic-CH),
1
1730 (C55O), 1270 (C-O-C), 1169 (C-N-C), 1151 (C-O), 719 (Ar-H); H NMR
(300 MHz, CDCl3 þ DMSO-d6): 9.66 (s, 1H, O-H), 6.5–8.5 (m, 5H, Ar-H),
5.5–5.3 (m, 2H, 30and 40-H); 5.02–5.09 (m, 1H, 20-H, anomeric proton), 4.66
(d, 1H, 10-H, anomeric proton), 4.10 (dd, 2H, 60-H2), 3.79–3.84 (m, 1H, 50-H);
13C NMR (100 MHz, CDCl3 þ DMSO-d6): 164 (C-4) (s, C55O) 162 (C-6)
(s, C55O), 149 (C-2) (s, C55O), 120–160 (aromatic C-atom), 118 (C-5, spiro
C-atom), 103 (C-10, anomeric C-atom), 83 (C-20, anomerþic C-atom), 76 (C-50),
74 (C-30), 62 (C-40), 54 (C-60); FAB-MS: m/z 456 (M , C22O9N2H20), 278
(C16O3N2H10), 201 (C11O3N2H5), 124 (C2O3N2).
2,3-a-D-Galactopyrano-7-o-tolyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,
10-triones 4d. IR (KBr): 3211 (-OH), 3180 (-NH), 3052 (Ar-CH), 2864 (galacto-
sidic-CH), 1731 (C55O), 1265 (C-O-C), 1175 (C-N-C), 1159 (C-O), 710 (Ar-H); 1H

Galactopyranosyl-Derived Spiro Barbiturates
669
NMR (300 MHz, CDCl3 þ DMSO-d6): 11.27 (s, N-H), 9.79 (s, O-H), 6.5–8.5
(m, 4H, Ar-H), 5.6–5.2 (m, 2H, 30and 40-H), 5.03–5.13 (m, 1H, 20-H, anomeric
proton), 4.62 (d, 1H, 10-H, anomeric proton), 4.09 (dd, 2H, 60-H2), 3.75–3.80
(m, 1H, 50-H), 2.23 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3 þ DMSO-d6):
162 (C-4) (s, C55O), 160 (C-6) (s, C55O), 154 (C-2) (s, C55O), 120–160
(aromatic C-atom), 119 (C-5, spiro C-atom), 103 (C-10, anomeric C-atom), 87
(C-20, anomeric C-atom), 79 (C-50), 72 (C-30), 65 (C-40), 58 (C-60), 20 (Ar-CH3);
FAB-MS: m/z 394 (Mþ, C17O9N2H18), 216 (C11O3N2H8), 201 (C10O3N2H5),
125 (C4O3N2H).
2,3-a-D-Galactopyrano-7,9-di-o-tolyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-
6,8,10-triones 4e. IR (KBr): 3214 (-OH), 3061 (Ar-CH), 2890 (galactosidic-CH),
1
1729 (C55O), 1269 (C-O-C), 1173 (C-N-C), 1148 (C-O), 710 (Ar-H); H NMR
(300 MHz, CDCl3 þ DMSO-d6): 11.23 (s, N-H), 9.79 (s, O-H), 6.5–8.5 (m, 8H,
Ar-H), 5.5–5.1 (m, 2H, 30and 40-H); 5.03–5.11 (m,1H, 20-H, anomeric proton),
4.69 (d,1H,10-H, anomeric proton), 4.11 (dd, 2H, 60-H2), 3.73–3.79 (m, 1H, 50-
H), 2.30 (s, 6H, CH3); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 164 (C-4)
(s, C55O), 161 (C-6) (s, C55O), 157 (C-2) (s, C55O), 120–160 (aromatic
C-atom), 119 (C-5, spiro C-atom), 103 (C-10, anomeric C-atom), 89 (C-20,
anomeric C-atom), 78 (C-50), 73 (C-30), 64 (C-40), 55 (C-60), 20 (Ar-CH3); FAB-
MS: m/z 484 (Mþ, C24O9N2H24), 306 (C18O3N2H14), 291 (C17O3N2H11), 215
(C11O3N2H7), 200 (C10O3N2H4), 124 (C4O3N2).
2,3-a-D-Galactopyrano-7-o-anisyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-6,8,
10-triones 4 h. IR (KBr): 3219 (-OH), 3184 (-NH), 3054 (Ar-CH), 2871 (galac-
tosidic-CH), 1744 (C55O), 1269 (C-O-C), 1174 (C-N-C), 1146 (C-O), 710 (Ar-
H); 1H NMR (300 MHz, CDCl3 þ DMSO-d6): 11.31 (s, N-H), 9.81 (s, O-H),
6.5–8.5 (m, 5H, Ar-H), 5.6–5.2 (m, 2H, 30and 40-H), 5.03–5.16 (m, 1H, 20-H,
anomeric proton), 4.67 (d, 1H, 10-H, anomeric proton), 4.12 (dd, 2H, 60-H2),
3.78–3.83 (m, 1H, 50-H), 3.92 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3 þ
DMSO-d6): 166 (C-4) (s, C55O), 163 (C-6) (s, C55O), 158 (C-2) (s, C55O),
120–160 (aromatic C-atom), 119 (C-5, spiro C-atom), 102 (C-10, anomeric
C atom), 87 (C-20, anomeric C-atom), 78 (C-50), 73 (C-30), 66 (C-40), 59 (C-60),
57 (CH3, Ar-OCH3); FAB-MS: m/z 410 (Mþ, C17O10N2H18), 232 (C11O4N2H8),
201 (C10O3N2H5), 125 (C4O3N2H).
3-a-D-Galactopyrano-7,9-di-o-anisyl-1,4-dioxo-7,9-diaza-spiro[4,5]deca-
6,8,10-triones 4i. IR (KBr): 3212 (-OH), 3059 (Ar-CH), 2868 (galactosidic-CH),
1
1737 (C55O), 1271 (C-O-C), 1172 (C-N-C), 1153 (C-O), 710 (Ar-H); H NMR
(300 MHz, CDCl3 þ DMSO-d6): 11.39 (s, N-H), 9.87 (s, O-H), 6.5-8.5 (m, 8H,
Ar-H), 5.6–5.2 (m, 2H, 30and 40-H), 5.03–5.13 (m, 1H, 20-H, anomeric
proton), 4.65 (d, 1H, 10-H, anomeric proton), 4.12 (dd, 2H, 60-H2), 4.03 (s, 6H,
OCH3), 3.78 (m, 1H, 50-H); 13C NMR (100 MHz, CDCl3 þ DMSO-d6): 166 (C-
4) (s, C55O), 163 (C-6) (s, C55O), 158 (C-2) (s, C55O), 120–160 (aromatic

V. N. Ingle et al.
670
Scheme 1
C-atom), 119 (C-5, spiro C-atom), 102 (C-10, anomeric C-atom), 87 (C-20,
anomeric C-atom), 78 (C-50), 73 (C-30), 66 (C-40), 59 (C-60), 56 (CH3, Ar-
OCH3); FAB-MS: m/z 516 (Mþ, C24O11N2H24), 338 (C18O5N2H14), 307
(C17O4N2H11), 231 (C11O4N2H7), 200 (C10O3N2H4), 124 (C4O3N2) (Scheme 1).
ACKNOWLEDGEMENT
The authors are thankful to Director, SAIF, Chandigarh and CDRI, Lucknow,
for providing necessary spectral data of the compounds, Head, Department of
Pharmaceutical Science R.T.M. Nagpur University, for screening antimicrobial

Galactopyranosyl-Derived Spiro Barbiturates
671
activity, and Head, Department of Chemistry, R.T.M. Nagpur University,
Nagpur, for providing necessary laboratory facilities.
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