REACTIONS OF SH-SUBSTITUTED PURINE BASES WITH GLYCIDOL
625
Thus, the regioselectivity of S-alkylation of I IV
with glycidol tends to grow with decreasing tempera-
ture, but does not exceed 70% even at temperatures
from 35 to 40 C.
we found previously [1], 8-benzylthioadenine is regio-
selectively alkylated with glycidol at the 3-N-position
of the purine system owing to the steric effect of the
benzylthio group [1]. Using this approach, we per-
formed the reaction of 6-benzylthiopurine IX with
glycidol and obtained compound X.
To perform N-alkylation of SH-purine bases with
glycidol, it is necessary to protect the SH group. As
SCH2C6H5
N
SCH2C6H5
N
N
N
DMF
+ CH2 CHCH2OH
NH
N
K2CO3
O
N
N
CH2CHOHCH2OH
IX
X
The structure of X was confirmed by NMR and UV
spectroscopy. The absence of the bathochromic shift
3.50 t (2H, CH2OH), 3.40 3.80 m (3H, SCH2CHOH),
8.10 s (1H, C2H), 8.45 s (1H, C8H). UV spectrum
of the band with
293 nm in the case of X rela-
(H2O, pH 7), nm:
290.
tive to IX unambigmuoaxusly indicates that glycidol adds
to the 9-N atom of the purine system. The NMR spec-
trum contains signals characteristic of the 9-N-dihy-
droxypropyl substituent.
max
A 0.2-g portion of glycidol was added to a solution
of 0.5 g of I in 50 ml of liquid ammonia containing
10% H2O. The solution was stirred for 2 h at a tem-
perature from 35 to 40 C. After evaporation of
ammonia, the residue was acidified with HCl to pH 5.
The precipitate was recrystallized from water. Yield
of V 0.52 g (70%).
The immunostimulating activity of the compounds
prepared was assessed using as the model the immu-
nodepression caused by a known immunodepressant,
azathioprine. Experiments were performed with SVA
line mice; the test samples were administered paren-
6-Hydroxy-8-(2,3-dihydroxypropylthio)purine
VI. A 0.015-mol portion of glycidol was added to a
solution of 0.01 mol of II in 50 ml of water, contain-
ing 0.012 mol of NaOH. The solution was stirred at
room temperature for 3 h and neutralized with HCl.
Water was evaporated in a vacuum to a minimal
volume. The precipitate was filtered off, washed with
water, and dried at 100 110 C. Yield of VI 0.007 mol
1
therally in the dose of 0.5 mg kg over a period of
8 days against the background of immunodepression.
All the samples showed moderate stimulating activity:
the death percentage decreased to 50 70%, against
80% in the control group.
EXPERIMENTAL
1
(70%), mp 180 185 C (dec.), Rf 0.45. H NMR spec-
trum, , ppm: 3.20 3.65 m (5H, CH2OH, CHOH,
SCH2), 4.80 m (1H, CH2OH), 5.10 m (1H, CHOH),
8.10 s (1H, C2H). UV spectrum (H2O, pH 1), nm:
1
The H NMR spectra were recorded on a Bruker
AC-200 spectrometer in DMSO-d6 (internal reference
TMS), and the UV spectra, on a Specord spectropho-
tometer. The TLC analysis was performed on Silufol
UV-254 plates in the system n-butanol ethanol water,
4 : 1 : 1.5.
1
2
273,
278. Found, %: C 39.41, 39.57; H
max
max
4.23, 4.35; N 23.08, 23.20; S 12.92, 13.11. C8H10N4
O3S. Calculated, %: C 39.67; H 4.16; N 23.13; S
13.23.
6-(2,3-Dihydroxypropylthio)purine V. A mixture
of 0.01 mol of I and 0.02 mol of glycidol in 50 ml of
absolute DMF in the presence of a catalytic amount of
anhydrous K2CO3 was stirred at room temperature for
12 h. After distilling off DMF in a vacuum, the re-
sidue was treated with ethanol. The precipitate was
filtered off, recrystallized from water, and dried at
100 110 C. Yield of V 0.006 mol (60%), mp 195
197 C (dec.) (published data: mp 196 197 C [4],
The reaction of II with glycidol in wet liquid am-
monia was performed similarly to I. Yield of VI 71%.
2-Amino-6-hydroxy-8-(2,3-dihydroxypropyl-
thio)purine VIII. The reaction of IV with glycidol
was performed similarly to preparation of VI. Yield of
VIII 0.0075 mol (75%), mp 196 198 C, Rf 0.40.
1H NMR spectrum, , ppm: 3.10 3.80 m (5H, CH2OH,
CHOH, SCH2), 4.80 m (1H, CH2OH), 5.10 m (1H,
CHOH), 6.40 s (2H, NH2). UV spectrum (H2O, pH
1
178 179 C [9]), Rf 0.50. H NMR spectrum, , ppm:
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004