Structural modifications of ascorbic acid by the introduction of lipophilic
moieties has led to derivatives with increased stability against thermal a
nd oxidative degradation. Two series of new lipophilic ascorbic analogues w
ere synthesized to obtain antioxidants devoid of autooxidant properties: 4-
benzoyl-3-hydroxyfuran-2(5H)-ones (3a-j) and 4-acetyl-5-aryl-3,4-dihydrofur
an-2(5H)ones (5a-f).
These compounds were submitted to three different tests: reduction of the s
table free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH); superoxide-anion
scavenging assay; and lipid-peroxidation assay. Most compounds interacted w
ith DPPH: at a concentration of 5 x 10(-3) M, the reducing activity of 4-be
nzoyl derivatives, 3c and 3h, was more than 50%; under the same conditions,
the rate of inhibition for 4-acetylbutanolides, 5a and 5f, reached 60.6% a
nd 87.3%, respectively; 93.3% inhibition was observed with ascorbic acid. I
n the superoxide-anion scavenging assay, at a concentration of 1 mg mL(-1),
4-benzoyl derivatives, 3g and 3i, exhibited a good activity, with IC50 (do
se resulting in 50% inhibition) values of 1.45 and 1.35 x 10(-3) M, respect
ively. 4-Acetylbutanolide 5f, significantly inhibited the Fe2+/ADP/ascorbat
e-induced lipid peroxidation of rat liver microsomes with an IC50 of 4.9 x
10(-4) M.
This study demonstrates that enol functions in the structure of ascorbic ac
id analogues are not absolutely essential to bring about antioxidant effect
s.