Idonic acid

An application to n-xylose (LXII) of the Fischer synthesis of 2-amino hexonic acids from pentoses would lead theoretically to a mixture of 2-amino-D-gulonic acid (LXIII) and 2-amino-D-idonic acid (LXIV). 

Deamination of 2-amino-2-deoxy-D-idonolactone (27) with nitrous acid led, after oxidation with nitric acid, to 2,5-anhydro-D-glucaric acid39,42 (28). As deamination of 2-amino-2-deoxy-D-idonic acid, followed by oxidation, gave 2,5-anhydro-D-idaric acid, the different behavior of the lactone 27 must be due to an attack on the incipient carbonium-ion at C-2 by a favorably disposed hydroxyl group in the molecule, such as at C-5. 

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. 

Methods for the preparation of L-idonic acid and L-xylose were discussed in Ref. 1. 

Two different mechanisms for the formation of L-xyZo-2-hexulosonic acid (28) from L-sorbose (25) have been proposed, depending on the organism used for the fermentative oxidation. It was concluded280-283 that the metabolism of 25 by Pseudomonas aeruginosa IFO 3898 most probably follows the sequence 25 — L-idose (41) — L-idonic acid (42) — 28. Both 41 and 42 were isolated from the fermentation broth. With Gluconobacter melanogenus, it was concluded284-287 that 25 is... 

It is probable that the mixture of L-idonic acid (42) and L-gulonic acid (47) obtained from L-xylose by way of cyanohydrins 71 may be directly converted into 28 by fermentative oxidation, as it is known that Pseudomonas aeruginosa371 73-3 and Acetobacter suboxy-... 

Gray.437 It was determined that, at a variety of temperatures and pressures, using Raney nickel as the catalyst, the calcium salt of 85 was converted, in good yield, into an essentially 1 1 mixture of the calcium salts of 42 and 86. This ratio was determined by isolating 2,4 3,5-di-O-benzylidene-L-idonic acid (68) from the reaction mixture. 

The patents in Refs. 447-450 appeared between 1959 and 1965, and concerned the reduction of 85 (or other salt) to L-idonic acid. The Chem. Abstr. citation suggested that, under the conditions reported, L-idonic acid was the major product. 

Finally, methyl 2,3,4,6-tetra-0-acetyl-D-xfy(o-5-hexulosonate (84) has been reduced396 by hydrogenation in the presence of Raney nickel, to afford the corresponding derivatives of L-idonic and D-gluconic acid in the ratio of 9 1, from which the L-idonic acid derivative was isolated in 48% yield after acetylation. Interestingly, when reduced with sodium borohydride, 2,3,4,6-tetra-0-benzyl-lV,lV-di-methyl-D-xi//f)-5-hexulosonamide afforded the L isomer as the major component (no ratio given)459 as well. 

Several attempts to reduce D-ry/o-5-hexulosonate (85) selectively to L-idonic acid (42) by fermentative reduction have been reported.460-464 An enzyme system isolated from Fusarium oxysporum has been re-... 

An alternative synthesis468 of L-idonic acid is shown in Scheme 15. On oxidation with periodate, 1,2-O-isopropylidene-a-D-glucofuranose (56) yields the protected dialdose 91. When 91 is treated with hydrogen cyanide, a mixture (92) of the Q-gluco and L-tdo nitriles results, with the D-gluco nitrile preponderating. Hydrolysis affords L-iduronic... 

In addition, L-sorbose has been isomerized in low yield to L-idose by using Pseudomonas aeruginosa. The L-idose was not accumulated, but was converted into L-idonic acid. 

In one, the insoluble, binary salt cadmium(II) chloride L-idonate was formed, and it was separated from the soluble cadmium D-glucon-ate by filtration. It was claimed that >90% of the L-idonic acid could be isolated by this procedure.470... 

The second procedure, and probably the more effective [if, as here, the desired product is L-xy/o-2-hexulosonic acid (28)], is based on simultaneous, fermentative oxidation of L-idonic acid (42) to 28, and fermentative decomposition of D-gluconic acid (86). Efforts directed toward the simultaneous oxidation of 42 and decomposition of D-gluconic acid will be summarized, as well as efforts made to convert 42 efficiently into 28 by fermentative oxidation. 

Thus, D-glucose (8) may be efficiently converted into calcium D-xy/o-5-hexulosonate (85) which, on hydrogenation, affords an —-7 3 mixture of L-idonic acid (42) and D-gluconic acid (86) that may be efficiently converted into L-xy/o-2-hexulosonic acid (28). The overall yield of 28 is 50% (see Scheme 13). Much of this chemistry has been reviewed.100-102 Should a more selective reduction of 85 be found, this... 

Inhibited collagen- or thrombin-induced human platelet aggregation specific inhibitor of arach-idonic acid release 383,384... 

The structure of 138 was elucidated, shortly after its isolation, in extensive contributions by many groups. Several important discoveries relating to its constitution were reported in 1933, the same year in which the first successful synthesis was described (see Refs. 274, 324). Thus, the group at the University of Birmingham335 found that the primary oxidation product of 138, the 2,3-diulosono-lactone 148 (dehydroascorbic acid), could be quantitatively oxidized by sodium hypoiodite to generate oxalic acid and L-threonic acid (Scheme 16), which was identified as the crystalline tri-O-methyl-L-threonamide. These results established the stereochemical relationship between 138 and L-gulonic (and L-idonic) acid. The work that provided support for the structure of L-ascorbic acid has been summarized in several reviews.274,336... 

D-Idonic acid, 2-amino-2-desoxy-, II, 62 D-Idonic lactone, reduction of, IV, 365 L-Idopyranose, 1,4-anhy dro-2,3,6-tri-methyl-, II, 69... 

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