L-Gulonolactone

Vitamin C is L-ascorbic acid (chemically 2-oxogulonolactone). The two hydroxyl groups have acidic properties. By releasing a proton, ascorbic acid therefore turns into its anion, ascorbate. Humans, apes, and guinea pigs require vitamin C because they lack the enzyme L-gulonolactone oxidase (tl.3.8), which catalyzes the final step in the conversion of glucose into ascorbate. 

Related imino alditols such as azepanes or lactam derivatives have been obtained and have shown to be glycosidase inhibitors [96, 100]. Both d- and l-gulonolactone have been converted into polyhydroxylated 1,6-aldonolactams of type 79 in a sequence of straightforward functional transformations, including sulfinylation of the corresponding aldonolactone-derived acetonides 76 that gave 5,6-cyclic sulfites 77 (Scheme 23) [101]. The latter reacted with sodium azide... 

A L-/wco-related analogue (71) of isofagomine [61], which was recently prepared from D-ribose by Ichikawa et al. following previously established chemistry [63,121], was found to be an a-L-fucosidase inhibitor with Kj 8 pmol/1. No inhibition was found with tetrazole derivatives such as (72) [ 122] obtained from L-gulonolactone. 

The major 1,3-dioxane could be separated by column chromatography but the diastereoisomeric 1,3-dioxolane derivatives could not be separated [Scheme 3.89],39 The strong preference for 1,3-dioxane formation is underscored in the benzylidenation of L-gulonolactone depicted in Scheme 3.90. Two different products formed depending on the reaction conditions, but in neither case was a 1,3-dioxolane ge tie rated.165... 

Preparative Methods prepared in two steps from commercially available L-gulonolactone via ketalization and oxidative cleavage with sodium periodate at pH 5.5. Also obtained from l-ascorbic acid via (i) ketalization, reduction (lithium aluminum hydride) and oxidative cleavage (sodium periodate), or (ii) ketalization and oxidative fragmentation using hydrogen peroxide and hypochlorous acid. ... 

Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates, thus making ascorbic acid an essential in the diet. 

L-Gulonolactone Figure 8.57. Outline of ascorbic acid biosynthesis. 

Diketogulonate cannot be reduced back to ascorbate. Most animals synthesize ascorbate using the path shown in Fig. 7.7, but primates including humans have accumulated mutations in the gene for L-gulonolactone oxidase and cannot synthesize ascorbate de novo. They require a dietary source of vitamin C to compensate for the gradual loss of dehy-droascorbate. The current Recommended Dietary Allowance (RDA) from the US Food and Drug Administration is 60-95 mg/day. 

---