STUDIES ON THE SYNTHESIS OF 2,6-DISUBSTITUTED FATTY ACID ESTERS OF ASCORBIC ACID: ESTERIFICATION VIA ACYL CHLORIDES IN DIMETHYLFORMAMIDE
Fernando De La Torre, Edward Alexander, Jose Rizo, Sonjiala Hotchkiss, Samantha Barrera, Adam Abdi, Naquiba Williams, Akinyemi Olowu, Emmanuel Gutierrez, Alberto Palacios.
San Diego Mesa College, San Diego, CA.
Although widely appreciated for its antioxidant properties, ascorbic acid (AA) has also gained recognition as an allosteric inhibitor of the glycolytic enzymes phosphofructokinase-1 (rPFK-1) and lactose dehydrogenase (rLDH). Furthermore, research has implicated the mono- and di-substituted fatty acid esters of AA as potential cancer therapeutics because of their increased inhibition of rPRK-1 and rLDH. This study purposefully explores the synthesis of 2,6-disubstituted derivatives of AA using pyridine in dimethylformamide (DMF). By using this modified esterification method initially using lauroyl chloride, our hypothesis is that the major products using any acyl chloride (AC) are 2,6-disubstituted esters regardless of the molar ratio of AA to AC. A minor presence of mono-esters is also detected. A mechanism is proposed involving the formation of an intermediate carbanion on carbon 4 which leads to 6-substituted and 2,6-disubstituted esters. AA was dissolved in DMF containing pyridine followed by the slow addition of an AC. The reactions were carried out at both 1:1.5 and 1:1 molar ratios of AA to various ACs, including lauroyl and octanoyl chloride. Additionally, a parallel reaction was run using the 6-substituted derivatives and their respective ACs at a 1:1.1 molar ratio. After distilling off the DMF at reduced pressure, the residual oil was treated with another solvent capable of displacing the di-substituted products, thus isolating the compounds. The reactions were followed closely by thin layer chromatography (TLC), and spectroscopic techniques (IR/NMR). TLC confirmed that the isolated products were solely di-substituted after the procedure and the residual oil contained a mixture of the mono- and di-esters.