3-Methylascorbic acid

The demonstration by Knox that ascorbic acid is a cofactor in tyrosine metabolism has been discussed earlier. Though ascorbic acid is essential both for this purpose and for the prevention of scurvy, the latter is probably not due to any appreciable extent to inadequate tyrosine metabolism (e.g., 723). Further experiments with liver preparations have shown that a number of other substances can replace ascorbic acid, o-isoascorbic acid being as effective as ascorbic acid itself (160, 489). Many other ene-diols are effective in tissue homogenates (522,791) but not necessarily in the intact animal, where poor absorption or retention reduces their efficacy (661,975). Substances such as 3-methylascorbic acid (791), which do not contain an ene-diol structure, cannot replace ascorbic acid. 

More recently, Brimacombe et al. (18) have also shown C2 alkylation of an ascorbic acid derivative in their attempted use of ascorbic acid as a synthon for the synthesis of spirodilactones. Dealkylation of 2-0-(E)-cinnamoyl-5,6-0-isopropylidene-3-0-methylascorbic acid, 15, with lithium iodide in DMSO afforded the C2 alkylated isomer, 16. It would appear that under conditions of reversible dealkylation at oxygen, C2 alkylation acts as a sink for the equilibrating mixture. 

Methylascorbic acid is present in the urine of rats and is likely a minor metabolite, formed by action of the enzyme catechol-O-methyl transferase (57,64). 

L-Ascorbic acid Sodium-L-ascorbate 2,3-Di-O-methylascorbic acid 3-Benzoyl ascorbate 5,6-Isopropylidene-L-ascorbic acid 3-0-[ (Dimorpholino)phosphinate]-5,6-0-isopropyli-dene-L-ascorbate Potassium-L-ascorbate 2-sulfate Cysteine HCl Cysteine free base D-Isoascorbic acid Dehydro-L-ascorbic acid... 

Methylation of L-ascorbic acid with diazomethane has thrown some light on the tautomeric nature of the vitamin. The greater acidity of the C-3-OH enables it to be titrated with ethereal diazomethane to give 3-0-methylascorbic acid. This reaction, however, is also accompanied by the formation of a small quantity of 1-methyl- -L-ascorbic acid, presumably from a minor tautomer. Both of these compounds undergo further methylation with ethereal diazomethane to give 2,3-di-O-methyl-L-ascorbic acid and 1,2-di-O-methyl- -L-ascorbic acid respectively (Figure 4.9). 

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