Reactive oxygen species (ROS) are believed to play a role in development of several diseases. L-ascorbic acid (AsA) is a kind of excellent antioxidant, but its instability in solution and hydrophilicity limits the wide use of it. Structural modifications of AsAby the introduction of lipophilic moieties can lead to derivatives with increased stability against thermal and oxidative degradation. In this study, a series of 6-O-acyl-L-ascorbic acid-2-O-phosphates (6-Acyl-AA-2Ps) were synthesized from a stable AsA derivative, L-ascorbic acid-2-phosphate ester magnesium (AA-2P) and long-chain fatty acids, act as radical scavengers for ROS and free radicals. ROS scavenging ability was investigated by CDCFH method in 95-D cells. The effect of 6-Acyl-AA-2P series on viability of 95-D cells was also studied by MTT method. All the synthesized compounds show stronger ROS scavenging ability and cytotoxicity than those of AsA. High-performance liquid chromatography assay demonstrates that 6-Acyl-AA-2Ps are stable in RPMI-1640 medium and can easily permeate cell membrane and be converted into AsA and L-ascorbic acid-2-phosphate ester. The results also show that the activity of 6-Acyl-AA-2Ps increases with a decrease in the length of the alkyl chain but cytotoxicity decreases. The optimum length of alkyl side chain is 12 carbons. In summary, 6-Laur-AA-2P should be one of the best candidates for the development of an efficient new AsA derivative and should be further investigated in detail.