Synthesis and antimicrobial studies of some bis-glycosyl isodithiobiurets

Article abstract of DOI:10.1155/2010/798145

Certain 2-S-tetra-O-benzoyl-D-glucopyranosyl-1-aryl-5-tetra-Oacetyl-β-D- galactopyranosyl-2, 4- isodithiobiurets have been synthesized by the interaction of tetra-O-acetyl-β-D-galactopyranosyl isothiocyante and various S- tetra-O-benzoyl-D- glucopyranosyl-1-aryl isothiocarbamides. The newly synthesized compounds were screened for their antimicrobial activities.

Full text of DOI:10.1155/2010/798145

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(3), 795-798
http://www.e-journals.net
Synthesis and Antimicrobial Studies of
Some Bis-Glycosyl Isodithiobiurets
PRASHANT R. MAHALLE and SHIRISH P. DESHMUKH*
P. G. Department of Chemistry,
Shri Shivaji College, Akola - 444 001 (M.S.), India.
prmahalle@rediffmail.com
Received 22 October 2009; Accepted 15 December 2009
Abstract: Certain 2-S-tetra-O-benzoyl-D-glucopyranosyl-1-aryl-5-tetra-O-
acetyl–β-D- galactopyranosyl-2, 4- isodithiobiurets have been synthesized by
the interaction of tetra-O-acetyl-β-D-galactopyranosyl isothiocyante and
various S- tetra-O-benzoyl-D- glucopyranosyl-1-aryl isothiocarbamides. The
newly synthesized compounds were screened for their antimicrobial activities.
Keywords: Synthesis, Antimicrobial studies, Bis-glycosyl isodithiobiurets
Introduction
Aryl/alkyl isothiocarbamides, due to their basic nature are found to interact with
isothiocyante to form corresponding isodithiobiurests. Several non-glycosidic
isodithiobiurests are known for their anticonvulsant and hypnotic activities1, several
S-glucosides have been described in the literature to possess antimicrobial activities2.
Glycopyranosyl isothiocyanates are attractive synthons in organic chemistry due to their
availability and their tendency to undergo nucleophilic additions and cycloadditions. Several
N-glycosides have been found several applications in industries as carbohydrate based
detergents3 and in medicine as antitumour4 and antitubercular5 activities.
In view of applications of all the compounds described above and our interest in the
synthesis of bis glycosyl isodithiobiurets, we report the synthesis of 2-S-tetra-O-benzoyl-D-
glucopyranosyl-1-aryl-5- tetra-O-acetyl-β-D-galactopyranosyl-2, 4-isodithiobiurets by the
interaction of tetra- O- acetyl- β-D- galactopyranosyl isothiocyante and various S- tetra-O-
benzoyl -D- glucopyranosyl - 1-aryl isothiocarbamides.
Experimental
Melting points are uncorrected. Optical rotations [α]D were measured on a Equip-Tronics
digital polarimeter model no. EQ 800 in CHCl3 at 39 C. IR spectra were recorded on a
0
Perkin-Elmer spectrum RXI (4000-450 cm-1) FTIR spectrometer. 1HNMR were obtained on

796
S. P. DESHMUKH et al.
a Bruker DRX-300 (300 MHz FT NMR) NMR spectrometer for a sample in CDCl3 solution
with TMS as an internal reference. The mass spectra were recorded on a Joel - SX 102 FAB
Mass spectrometer.
Tetra-O-acetyl- β -D - galactopyranosyl isothiocyanate (1)
Tetra-O-acetyl- β - galactopyranosyl isothiocyanate (2) was prepared from tetra-O-acetyl- α
- galactopyranosyl bromide using lead thiocyanate in xylene medium10.
S - tetra-O - benzoyl -D - glucopyranosyl 1- aryl isothiocarbamides (2a-g)
S-Tetra-O- benzoyl -D- glucopyranosyl 1- aryl isothiocarbamides have been prepared by the
methods described earlier which involves interaction of tetra-O-benzoyl-D-glucopyranosyl
bromide with various aryl isothiocarbamides11.
2-S-tetra-O-benzoyl-D-glucopyranosyl-5-tetra-O-acetyl- β-D -galactopyranosyl - 1
- aryl - 2,4 isodithiobiurets (3a- g)
2-S-tetra -O- benzoyl -D- glucopyranosyl-5-tetra-O- acetyl- β-D-galactopyranosyl-1- aryl 2,
4 isodithiobiurets (3a - g) were prepared by the condensation of S- tetra-O-benzoyl-D-
glucopyranosyl 1-aryl isothiocarbamides (2a-g, 0.005 M) and
tetra-O-acetyl-β-D-
galactopyranosyl isothiocyanate (1, 0.005 M) in benzene for 4 h. After the reaction was
completed the solvent was distilled off and the sticky residue was triturated with petroleum
ether to give the solids. The characterization data of the synthesized products is given in the
Table 1.
Table 1. Characterization data of the synthesized products (3a-g).
Reagent: Tetra -O- acetyl-β-D-galactopyranosyl isothiocyanate; S - tetra – O - benzoyl - D -
glucopyranosyl - 1 - aryl - isothiocarbamides ( 2a-g).
Analysis
39
[α] D
( CHCl3)
%
Yield
m. p.
°C
Rf
(CCl4 : EtOAc)
S. No. Product
Found
%
Required
%
75.25°
(c, 0.94)
48.86°
N, 3.62
S, 5.85
N, 3.58
S, 5.61
N, 3.60
S, 5.49
N, 3.77
S, 5.48
N, 3.77
S, 5.55
N, 3.63
S, 5.71
N, 3.63
S, 5.56
N, 3.62
S, 5.85
N, 3.64
S, 5.54
N, 3.64
S, 5.54
N, 3.64
S, 5.54
N, 3.70
S, 5.64
N, 3.70
S, 5.64
N, 3.70
S, 5.64
0.77
(3:2)
0.79
(3:2)
0.81
(3:2)
0.83
(3:2)
0.66
(3:2)
0.79
(3:2)
0.75
(3:2)
1
2
3
4
5
6
7
55
57
64
55
56
59
65
115
132
142
135
152
129
166
3a
3b
3c
3d
3e
3f
(c,1.00)
39.71°
(c,1.03)
39.73°
(c,1.00)
91.22°
(c, 0.98)
69.54°
(c,1.00)
49.01°
(c,1.02)
3g
Satisfactory C and H analysis are found in all cases.
3a: IR (KBr):- υ 3468 (N-H); 2974 (Ar-H); 1730 (C=O); 1602 (C = N) 1373 (C-N);
1
1271 (C-O); 1095 (C=S). HNMR (CDCl3):- δ 8.65-7.26 (m, N-H and Ar-H); 5.44 – 3.97
(m, glucopyranosyl + galactopyranosyl protons); 2.17-1.08 (m, 4COCH3). Mass (FAB):-
331, 169, 105.

Synthesis and Antimicrobial Studies
797
3c: IR (KBr):- υ 3419 (N-H); 2973 (Ar-H); 1729 (C=O); 1602 (C = N) 1373 (C-N);
1
1270 (C-O); 1096 (C=S). HNMR (CDCl3): δ 8.3-7.25 (m, N-H and Ar-H); 5.77 – 3.95 (m,
glucopyranosyl + galactopyranosyl protons); 2.22-1.06 (m, 4COCH3). Mass (FAB):- 331,
169, 105.
3f: IR (KBr):- υ 3451 (N-H); 2972 (Ar-H); 1730 (C=O); 1602 (C = N) 1372 (C-N);
1271 (C-O); 1094 (C=S). 1HNMR (CDCl3): δ 8.65-7.26 (m, N-H and Ar-H); 5.44 – 3.97 (m,
glucopyranosyl + galactopyranosyl protons); 2.17-1.08 (m, 4COCH3). Mass (FAB):- 331,
169, 105.
Antimicrobial activity
All the compounds were screened for their antibacterial activity against pathogenic bacteria
such as E. coli, S. aureus, P. vulgaris and P. aregenosa by cup plate agar diffusion method12,13
,
at a concentration 100 µg/mL in DMSO by using the standard Amikacin at the same
concentration. All compounds were also screened for their antifungal activity against A.
niger and C. albicans by cup plate method at a concentration of 100 µg/mL in DMSO by
using the standard Fluconazole at the same concentration. The zone of inhibition was
measured in mm and is average of three readings. The readings are shown in Table 2.
Table 2. Antimicrobial activities of compounds (3a-g).
Compounds
Antibacterial activity Antifungal activity
E. coli S. aureus P. Vulgaris P. aregenosa C. albicans A. niger
17
-
-
15
13
-
-
-
09
08
-
14
15
14
-
3a
3b
11
19
11
17
11
09
23
-
21
-
21
-
3c
3d
13
18
-
-
14
-
19
15
08
25
-
11
-
14
19
-
3e
3f
09
25
-
-
-
3g
Amikacin
Fluconazole
23
-
-
15
-
21
Including well diameter of 5 mm.
From the above observations, it is clear that compounds 3c and 3e are active against
E.coli, S. aureus and P. aregenosa as compared to standard, while 3b, 3d, 3f and 3g show
low or moderate activity against the bacteria.
In antifungal activity, compounds 3a, 3b and 3e show good activity against C. albicans
while other are inactive and compounds 3a, 3b, 3c, 3e and 3f show good activity, while
others show low activity against A. niger.
Results and Discussion
Several 2-S-tetra-O-benzoyl-D-glucopyranosyl 1-aryl-5-tetra-O-acetyl-β-D-galacto-
pyranosyl-2, 4- isodithiobiurets (3a-g) have been synthesized by the interaction of tetra-
O-acetyl-β-D-galactopyranosyl isothiocyante (1) and various S-tetra-O-benzoyl-D-
glucopyranosyl-1-aryl isothiocarbamides (2a-g). All the products were recrystallised
form ethanol. The structures of all the synthesized products were developed on the basis
of usual chemical transformation and IR, NMR and Mass Spectral analysis6-9. The
newly synthesized compounds were screened for their antibacterial and antifungal
activities.

798
S. P. DESHMUKH et al.
CH2OAc
NH
CH2OBz
OAc
OAc
O
N
C
S
O
S
C
+
OBz
OBz
NHR
OAc
OBz
reflux
benzene
(1)
(2a-g)
CH2OAc
N
CH2OBz
O
C
S
NH
O
OAc
OAc
C
S
NHR
OBz
OBz
OAc
OBz
( 3 a - g )
Scheme 1
Where , R = (a) phenyl , (b) o – Cl phenyl , (c) m – Cl phenyl , (d) p – Cl phenyl, (e) o – tolyl, (f) m –
tolyl, (g) p – tolyl , Bz = COC6H5 , Ac = COCH3..
Acknowledgment
Authors are thankful to RSIC, CDRI Lucknow for providing the spectra and also to Dr. S. G.
Bhadange, Principal, Shri Shivaji College, Akola for providing necessary facilities.
References
1
2
3
Siddique N and Pandeya S N, Indian J Pharm., 1992, 24, 171-173.
Garcia Fernandez J M and Mellet C O, Adv Carbohydr Chem Biochem., 2000, 55, 35-135.
Prata C, Mora N, Lacombe J M, Maurizis J C and Pucci B, Carbohydr Res., 1999,
321, 4-14.
4
5
Todoulou O G, Papadaki-valiraki A E, Filippatos E C, Ikeda S and De Clercq E, Eur
J Med Chem., 1994, 29, 127-131.
Tripathi R P, Tiwari V K, Tewari N, Katiyar D, Saxena N, Sinha S, Gaikwad A,
Srivastava A, Chaturvedi V, Manju Y K, Srivastava R and Srivastava B S, Bioorg
Med Chem., 2005, 13, 5668-5679.
6
7
8
Isac-Garcia J, Calvo-Flores F G, Hernandez -Mateo F and Santoyo-Gonzalez F, Eur J
Org Chem., 2001, 383 - 387.
Blanco J L J, Barria C S, Benito J M, Mellet C O, Fuentes J, Santoyo-Gonzalez F and
Garcia Fernandez J M, Synthesis, 1999, 11, 1907-1914.
Pearson M S M, Robin A, Bourgougnon N, Meslin J C and Denianud D, J Org
Chem., 2003, 68, 8583-8587.
Saleh M A, Sulfur lett., 2002, 25(6), 235-237.
9
10
11
12
Mahalle P R, Korpe G V and Deshmukh S P, J Indian Chem Soc., 2008, 85, 953-958.
Bhagat S K and Deshmukh S P, Asian J Chem., 2002, 14, 243-246.
Mangte D V, Deshmukh S P, Bhokare D D, Deshpande A R, Indian J Pharm Sci.,
2007, 69(2), 295-298.
13
Matsumura S, Imai K, Voshikawa S, Kawada K and Uchibari T, JAOCS, 1990,
67(12), 996-1001.

International Journal of
Advances in
Organic Chemistry
International
International Journal of
International Journal of
Photoenergy
Medicinal Chemistry
Analytical Chemistry
Physical Chemistry
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
Volume 2014
International Journal of
Carbohydrate
Chemistry
Journal of
Quantum Chemistry
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
http://www.hindawi.com
Volume 2014
Volume 2014
Submit your manuscripts at
http://www.hindawi.com
Journal of
The Scientific
Analytical Methods
in Chemistry
World Journal
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com
http://www.hindawi.com
Volume 2014
Volume 2014
International Journal of
Journal of
Journal of
International Journal of
Bioinorganic Chemistry
Spectroscopy
Inorganic Chemistry
Electrochemistry
Applied Chemistry
and Applications
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
http://www.hindawi.com
Volume 2014
Journal of
Journal of
International Journal of
Chromatography
Journal of
Theoretical Chemistry
Catalysts
Research International
Chemistry
Spectroscopy
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Hindawi Publishing Corporation
http://www.hindawi.com
Volume 2014
Volume 2014
Volume 2014
Volume 2014
Volume 2014