Abstract
To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid
1
reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid
2
–
6a
,
b
. Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems
10
–
15
, respectively. Ethoxycarbonylamino derivate
5
reacted with some nucleophiles containing the NH
2
group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives
16
–
20a
,
b
. Compound
4
reacted with the same nucleophiles to give the methylidene amino derivatives
21
–
24a
,
b
. The fused compound
10
reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems
25
–
30
, respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi.