Vol. 30, No. 10 (2018)
Synthesis of 3-Phenylamino-4-phenyl-5-tetra-O-acetyl-β-D-glucopyranosylimino-1,2,4-dithiazolidines 2311
hydroxyl-β-D-glucopyranosylimino-1,3,4-dithiazolidine is
broadly referred as de-acetylated glucopyranosylimino
nucleoside.
The work also elucidates the mechanistic scheme for both
acetylated and de-acetylated glucopyranosylimino nucleosides
by using mass spectrometry.
Synthesis of acetylated nucleoside from glucose
Preparation of glucose pentaacetate: The synthesis
method opted for synthesis of glucose pentaacetate is reported
by Huang et al. [15]. In the particular process 40 mL of an ice
cold acetic anhydride was added to 0.25 mL perchloric acid.
The resultant pale yellow coloured solution was added gradu-
ally to 10 g of D glucose with constant shaking. The reaction
mixture was kept without disturbing for 15 min at room tempe-
rature. The solution was precipitated out in ice cold water. The
precipitate is of glucose pentaacetate. Glucose pentaacetate
was crystallized in methanol. Presence of glucose pentaacetate
was confirmed by observing melting point 110 °C (Scheme-
IV).
EXPERIMENTAL
All the precursor chemicals namely, glucose, ethanol,
methanol, acetic anhydride, acetic acid, benzene, chloroform,
xylene, carbon tetrachloride, red phosphorus were obtained from
make E-Merck.
Synthesis of acetylated nucleoside i.e. 3-phenylimino-4-
phenyl-5-tetra-oacetyl β-D-glucopyaranosyl imino-1,2,4-
dithiazolidine was carried out from glucose as starting material.
Furthermore acetylated nucleoside is de-acetylated to the actual
nucleoside.
Synthesis of brominating reagent: The brominating
reagent was prepared by using Hell-Volhard-Zelinsky process.
In the particular process, 30 mL of glacial acetic acid was taken
in conical flask and 3 g of red phosphorous was added. To this
mixture 7 mL of molecular bromine was added gradually with
constant shaking and cooling. The resultant mixture was allowed
to stand for 15 min at room temperature [10,11]. The solution
was then filtered through cotton filter in order to remove
suspended impurities (Scheme-I).
O
CH3
O
OH
O
O
O
O
H
H
O
H
H
CH3
CH3
HClO4
H
H
O
+
O
H3C
OH
H
H
O
O
HO
OH
O
O
H
OH
O
CH3
H
H3C
O
CH3
Scheme-IV: Reaction step-I
Synthesis of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl
bromide: 21.6 g of glucose pentaacetate was added to the
brominating reagent. The resultant solution was kept undis-
turbed at room temperature for 2 h. The reaction mixture was
mixed with 30 mL of carbon tetrachloride with vigorous shaking
for 15 min. The resultant mixture was poured in to the ice-
cold water. The carbon tetrachloride is separated out from
product. The product was washed several times with sodium
bicarbonate to remove excess of glacial acetic acid. Similarly,
product was also washed by sodium meta-bisulphide to remove
excess of bromide. Finally product was washed with water
several times. The layer of carbon tetrachloride was then dried
over anhydrous calcium chloride. The solvent was removed
through vacuum distillation to obtain the solid tetra-o-acetyl-
α-D-glucopyranosyl bromide. The product is crystallized from
petroleum ether and confirmed by melting point as 88 °C [16]
(Scheme-V).
O
OH
Br
O
Br Br
Red P
+
+
H C
3
OH
Scheme-I: Synthesis of reagent-I
Synthesis of lead isothiocyanate: Lead nitrate (33 g)
solution was mixed with 15 g of ammonium thiocyanate. The
white coloured granular lead thiocyanate was obtained. The
granules were filtered and washed with distilled water and
dried in an oven at 50 °C [12] (Scheme-II).
Pb(NO3)2 + 2(NH4SCN) → Pb(SCN)2 + 2NH4NO3
Scheme-II: Synthesis of reagent-II
O
CH3
O
CH3
Synthesis of N-pheyl-S-chloro isothiocarbamoyl chloride:
A solution of 7 mL phenyl isocyanate in 15 mL of chloroform
was prepared. Chlorine gas generated from 3.2 g of potassium
permangante and 20 conc. HCl was bubbled while maintaining
temperature below 10 °C [13]. After addition of chlorine the
reaction mixture turned to yellow colour. This yellow reaction
mixture was diluted with 40 mL dry petroleum ether. The solvent
was removed by dry distillation under vacuum. The whole
process of distillation is repeated till we obtained pale yellow
oil of N-phenyl-S-chloro isothiocarbamoyl chloride (Scheme-
III) [14].
O
O
O
O
O
O
H
H
H
H
O
OH
H
Brominating agent
CCl4
H
H3C
H3C
O
H
H
+
O
O
O
Br
Br
O
O
O
H
O
CH3
H
O
O
H3C
H3C
O
O
CH3
CH3
Glucose pentacetate
2,3,4,6-tetra-acetyl-
glucopyranosyl bromide
α
-D-
Scheme-V: Reaction step-II
Synthesis of 2,3,4,6-tetra-o-acetyl β-D-glucopyranosyl-
isothiocyanate: A solution of 20 g of tetra-O-acetyl-α-D-
glucopyranosyl bromide in 150 mL xylene was prepared.
To this solution 16 g of lead isothiocyanate was added. The
reaction mixture was refluxed for 3 h with frequent shaking.
The solution was allowed to cool and separated out by filtration
from lead bromide [9,17]. The xylene filtrate was added to
O
N
Cl
Cl
N
Chloroform KMnO4 and con.HCl
S
Scheme-III: Synthesis of reagent-III