Gulono-1, hydrolysis

A short synthesis of D-gulono-1,4-lactone (2) from the inexpensive and readily available D-xylose (34) was first reported by Fischer and Stahel,18 and subsequently by others,12,25-31 and is shown in Scheme 6. The addition of hydrogen cyanide to D-xylose (34) resulted in the formation of cyanohydrins 35 and 36 which, on hydrolysis, afforded a mixture of D-gulonic acid (4) and D-idonic acid (37). D-Gulono-1,4-lactone may be obtained in 30-33% yield by recrystallization of the reaction products. In a similar way, L-xylose (l-34) has been converted32,33 in high yield into a mixture of L-gulonic and L-idonic acids. 

When 2-4-0-ethylidene-D-glucofuranurono-6,3-lactone [obtained by the hydrolysis of thioacetal 61 (Ph = Et)] was treated with 5,5-dimethyl-l,3-cyclohexanedione (dimedone), 6-deoxy-6,6-bis(4,4-di-methyl-2,6-dioxocyclohexyl)-3,5-0-ethylidene-L-gulono-1,4-lactone (73) was formed in 71% yield.99... 

Lemer (29) reported a simple synthesis of L-erythrose that involves 2,3-di-O-isopropylidene-D-gulono-1,4-lactone (7b) as a key intermediate. Reduction of the lactone group of 7b with sodium borohydride, followed by periodate oxidation of the L-glucitol derivative, afforded 2,3-O-isopropy-lidene-L-erythrose. The free sugar may be readily obtained by acidic hydrolysis of the latter. 

C]gulono- 1,4-lactone. The hydroxyl groups at C-2 and -3 were protected by isopropylidenation, and the 5,6-glycol was oxidized by sodium periodate. Treatment of the resulting syrupy product with methanolic hydrogen chloride, followed by borohydride reduction and hydrolysis, afforded L-[5-,4C]arabinose. 

In procedure B, a similar method was followed. D-Glucaro-1,4 6,3-dilactone (20) was reduced to L-gulono-1,4-lactone (21) which, when treated with ammonia in methanol, afforded L-gulonamide (22). Oxidation of 22 with sodium hypochlorite gave L-xylose (23), which formed osazone 19 with phenylhydrazine. Hydrolysis of 19 afforded 9. 

L-Gulono-l,4-]actone (21) was converted383 into 1 by the procedure shown in Scheme 11. When 21 was treated with benzaldehyde-hy-drogen chloride, 74 was isolated in >65% yield.384 On oxidation with manganese dioxide, compound 74 gave 75 in 70-90% yield on hydrolysis with 70% acetic acid-water, 75 afforded 1 in 70% yield. That this is one of the few syntheses of 1 which does not have the cycliza-tion of 28 or 29 as its last step is noteworthy. Under different conditions of lysis, (methanolic hydrogen chloride), 75 is converted into 29, not 1. 

Lactone 30 on oxidation at C2 gives ketolactone (31), which on hydrolysis in acetic acid-water afforded L-ascorbic acid (Scheme 16). This synthesis and the Bakke-Theander synthesis are among the few syntheses that do not have as the last step the lactonization of an appropriate 2- or 3-keto sugar acid or derivative. The approach shown in Scheme 16, the protection of either the C2 or C3 hydroxyl group in an appropriate 1,4-lactone followed by the oxidation of the unprotected hydroxyl to a ketone and then by hydrolysis, can be generally used to convert L-gulono-, L-galactono, and L-talono-l,4-lactone to L-ascorbic acid (50). 

When L-gulono-l,4-lactone (29) was treated with benzaldehyde diethyl acetal, ethyl 3,5 4,6-di-0-benzylidene-L-gulonate (32) was formed (49) in greater than 90% yield (Scheme 17). This derivative can be converted eflBciently into L-ascorbic acid by oxidation (> 90%) followed by hydrolysis of the resulting product to ethyl 2-keto-L-gulonate (L-x io-hexulosonate) (86%) and lactonization by either acid or base (90% ) to L-ascorbic acid. 

Another kind of intervention in the anhydrohexose aldose equilibrium has been described for l,6-anhydro-/3-D-gulopyranose. The action of 40% aqueous hydrogen bromide and bromine at 80° causes simultaneous hydrolysis and oxidation to D-gulono-1,4-lactone.122... 

H And C n.m.r. methods have been used to determine the preferred conformations of the four D-pentono-1,A lactones and D-glucono-, D-mannono-, D-gulono- and D-galactono-1, -lactone. The kinetics of hydrolysis of D-glucono-l, 4-lactone have been examined in detail, and calcium D-arabinonate has been shown to epimerize to a mixture containing 8o of the D-ribo-lsomer at 137°C in the presence of calcium hydroxide. 

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