Gulono-1, oxidation

Anhydro-L-gulono-1,4-lactone (62) was prepared100 in 62% yield by the platinum-catalyzed oxidation of 1,4-anhydro-D-glucitol. Methyl 3,4,5-tri-0-acetyl-2,6-anhydro-L-gulonate (63, R = H) was obtained from D-glucuronic acid by way of the tetraacetate (63, R = OAc) and the thioglycoside101,102 (63, R = SPh) (76%), followed by reduction in the presence of Raney nickel to afford 63 (R= H) (68%). 

The most important oxidation product of L-gulono-1,4-lactone (I) is, without a doubt, L-ascorbic acid (6 vitamin C), and the most important oxidation product of L-gulonic acid (3) is L-xyZo-2-hexulosonic acid (5), which serves as a key intermediate in the commercial production of L-ascorbic acid. The literature covering the methods by which 1 or 3 (or derivatives thereof) has been converted into 6 or 5, as well as other methods for the preparation of 6, has been reviewed,1 and will not be discussed here. 

When 2,3-O-isopropylidene-D-gulono-1,4-lactone (52) was treated with sodium periodate, 3,4-O-isopropylidene-L-lyxurono-l,4-lactone (84) was formed26 this was converted in several steps into D-arabin-ose. Benzyl 2,4,5,6-tetra-O -benzyl-L-gulonate was oxidized to benzyl... 

Hall and Bischofberger177 found that, when 2,3 5,6-di-0-isopro-pylidene-D-gulono-1,4-lactone was oxidized with ruthenium(VIII) oxide and an excess of sodium periodate, it gave 2,3 5,6-di-0-isopro-pylidene-D-riho-4-hexulosono-l,4-[(R) or (S)]-lactol. Similar results were observed with 2,3 5,6-di-0-isopropylidene-D-mannono-1,4-lactone and 2,3 5,6-di-O-isopropylidene-D-allono-l,4-lactone. This oxidation presumably proceeds by way of lactone cleavage and oxidation of the free 4-hydroxyl group followed, on acidification by relac-tonization, and formation of the new lactol. 

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. 

Periodate oxidation of 5,6-O-isopropylidene-L-gulono-1,4-lactone (9a) gave 2,3-O-isopropylidene-L-glyceraldehyde in 69% yield. This compound was used to prepare 2,3-O-isopropylidene-L-glycerol and it was also condensed with amines and Wittig reagents (34). 

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. 

It was also found that L-gulono-1,4-lactone (21) is enzymically oxidized to L-ascorbic acid (1) in 40% yield by using an enzyme system isolated from a variety of natural sources, including rat livers and germinating peas.378 L-Galactono- 1,4-lactone (16) was also oxidized to 1 with this enzyme system. 

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. 

In animals, UDP-D-glucuronic acid is the precursor it loses UDP and the D-glucuronic acid/D-glucuronolactone is reduced at C-l, forming L-gulonic acid/L-gulono-1,4-lactone. The lactone is oxidized by microsomal L-gulono-1,4-lactone oxidase to ascorbate. This enzyme is not expressed in primates, as they have lost biosynthetic capacity for ascorbate. 

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... 

A suspension of 2 g. dehydro-L-ascorbic acid phenylosazone in an ethanolic soln. of CuClg refluxed 15 min. 1.7 g. 3,6-anhydro-3-phenylazo-2-oxo-L-gulono-5-lactone phenylhydrazone. F. e., and mild oxidants such as FeClg, s. H. El Khadem and S. H. El Ashry, Soc. (C) 1968, 2251. 

Besides GLOs of animal species, the terminal enzymes of biosynthetic pathways of ascorbic acid in bakers yeast and in sweet potato were highly purified. Nishikimi et al. (1978) purified L-galactono-7-lactone oxidase from mitochondria of the yeast. This enzyme catalyzes the oxidation of L-galactono-7-lactone approximately three times as fast as that of L-gulono-7-lactone using O2 as the electron acceptor. Its molecular mass (monomer) was determined to be 56,000 daltons. Bleeg and Christensen (1982) also purified the enzyme from bakers yeast and... 

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