الفهرس 
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Abstract
Thiouracil derivatives are well-established medications toward cancer
diseases. In continuation to our research drug discovery program, to find new
chemical structures acting toward cancer and AIDS.
We report here synthesizing new structures based on reacting 6-amino-2-
thiouracil with mono- and multi-function groups reagents to synthesize new
poly-nuclear compounds and glucosidation of the new synthesized
compounds and the reactions include also a photo-chemical reaction.
Reactions with 6-Amino-2- Thiouracil
Bromination of 6-amino-2-thiouracil (11), with equimolecular amount
of bromine in acetic acid yielded 6-amino-5-bromo-2-thiouracil (12).
Br, BrJ
.JL,NH
H,N N~S
H
II 12
Alkylation of each of 11 and 12 with halogeno-compounds III ethanolic
sodium ethoxide solution, yielded the 2-alkylthioderivatives 14(a-i).
+ RX
11 or 12 14(0-i)
11.12,14 R R,
0 H -Me
b H -Et
c H -CH,COOEt
d H -CH,COPh
e H -CH(COCHJ),
(
g
h
11,12,14 R R,
Br -Me
Br -Et
Br -CH,COPH
Br -CH(COCHJh
f
._...~-.._.._---.--.-------~-----”””I
The S-carboxymethyl derivative 17 was obtained by heating the kn
7-amino-2,3-dihydro-5H-thiazolo[3,2-aJpyrimidine-3,5-dione (16) with w
16 17
Heating under reflux a mixture of 11with chloroacetic
appropriate aromatic aldehyde, anhydrous sodium acetate, glacial acetic
and acetic anhydride afforded 18(a-d). Also 18(a-d) was obtained by h
under reflux a mixture of 17 with an appropriate aromatic aldehyde,
acetic acid, and acetic anhydride afforded 18(a-d).
0 0 f HO 0 ArCHO
o fw~/” C1CH2COOH I NNe.
HN N~S)
AcOHI AC20 )IN I NJ-.
S
- H AcOHI Ac.p
z H NCHO
17
I:;. 18 (a-d) \I
18 A<
a -C6Hs
b -C6H4OMe-p
c -C6H4C1-p
d -C4H)S~2
Heating compound 16 under reflux in absolute alcohol
aldopentoses namely, D-arabinose and D-xylose yielded the correspo
C-glycoside 19(a,b).
1~r.
I,,
fa ~OHOH
N HO
H,N I N~S ’” OH
- OH
- ClCH2COOH
/Dcarabinosc 0 fN~o~~ D-arabinose
Pyridine OH
J piperidine I J- ~ OH
H2N N S
19.
fo 0 HO
CICH2COOH N~H
/ D-xylose j J- ~ OH D-xylose
Pyridine HzN N S
/ piperidine OH
an 19b
tcid
ting
icial
The same reaction could be achieved in one pot-stepwise synthesis
starting from I and chloroacetic acid in pyridine and few drops of piperdine.
JN...H.
SH
Applying the same reaction condition on aldohexoses namely
D-g1ucose, D-galactose, and D-manose either by using compound 11 or 16 as
in case of aldopentoses afforded the corresponding C-glycosides 19(c-e) •
respectively.
fo 0 OH
IN~HO OH
H,N N~~
- OH
19<
I’d
with
nding
”)17’7
’<-
A modem, simple and conventional method could be reported h~.
cydization of both compounds 14(d,e) via acetylation mechanism.
cydized product 20(a,b) can be obtained by high quality and quantity.
,.---~
Me : o : ”rlu
/-- : 0 : R,
X.~·J( H,N N S R,
\
20(a,b)
20 R, R1
8- .cOMe· -Me
b -H -Ph
In addition to the proceeding of the expected acetylation mech .
the amino group was acetylated to produce to the class compound 2l(a,
unfortunately.
•
o R
~ {J-~R’
21 R, R,
• .cOMe ·Me
N N S b -H ·Ph
H
21(a,b)
compound 14d or 14b heated at 120 - 140 °c with poly phosph
acid as dehydrating agent was used as dehydrating agent, to furnish
corresponding thiazolo[3,2.aJpyrimidine derivatives 20(a,b) with
the amino group.
-
20 R, R2
a ~COMe ~H
b ~Me ~Ph
20(a,b)
Heating compound 14e with phenyl hydrazine and hydrazine hydrate
produced the class compound 22(a,b).
PbNHNH,
•
22a
An improved method, for the preparation of compound 23, is reported
here.
14a 23
””””””””””””””””””””””””””””””””””””””,( V )!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
Reacting 14a with aromatic amines, by fusion at 140°C, prod
promising class compound 24(a,b).
~x 24(0,b)
140°C
+
140 ±X 4
o -H
b -CI
I
Compound 11 reacted with carbon disulphide in pyridine
compound 25. The ’H-NMR, IR and mass spectra support structure”.<>”,
0
• {NH + 50s
HN NAs 2 H
11
25
6_Amino-2-thiouracil (11) was photo-oxygenated by
irradiated dioxane at room temperature in a pyrex glass vessel
pressure lamp to give I-amino -7,8- dioxa -2,4- diazabicyclo [4.2.01:
3,5- diane (26). This involves oxidation for thione group to oxo
the same time cycloaddition of singlet oxygen reaction to the d
took place to furnish the new dioxetane ring.