L-gulono-1,4-lactone

In ketones existing largely as the enol, palladium may prove effective in minimizing hydrogenolysis, Hydrogen was added slereoselectively to the least hindered side of L-ascorbic add (3) to give L-gulono-1,4-lactone (4)... 

The most efficient synthesis of L-gulono-1,4-lactone (1) entails the reduction of D-glucofuranurono-6,3-lactone (7), which can be obtained from D-glucose2 (see Scheme 1). Catalytic hydrogenation3-4 of 7 in the presence of Raney nickel afforded 1 in 81% yield. Alternatively, D-... 

When L-gulono-1,4-lactone was treated with acetaldehyde diethyl acetal in N,N-dimethylformamide-benzene in the presence of a catalytic amount of p-toluenesulfonic acid, 5,6-O-ethylidene-L-gulono-1,4-lactone (54) was formed86 in 61% yield (40%, recrystallized). It is interesting that compound 54 was clearly a mixture of diastereo-... 

It was reported that, when L-gulono-1,4-lactone was treated with benzaldehyde and concentrated sulfuric acid, 2,6 3,5-di-0-benzyli-dene-L-gulono-1,4-lactone was formed.78,87... 

A number of triply protected derivatives of L-gulono-1,4-lactone (1) have been prepared. When 1 was treated with 3 equivalents of tert-butylchlorodimethylsilane, 2,5,6- and 3,5,6-tri-0-(tert-butyldi-methylsilyl)-L-gulono-l,4-lactone were formed86 in >90% yield. When 3,5-O-benzylidene-L-gulono-l,4-lactone was treated with chlorotriphenylmethane, 3,5-0-benzylidene-6-0-trityl-L-gulono-l,4-lactone was isolated in 38% yield.86... 

These structures are drawn to show their relationship to L-gulono- 1,4-lactone, rather than in the conventional fashion with C-6 at the left. 

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%). 

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... 

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. 

C13H20O7 2,21 5,6-Di-0-isopropylidene-[2-C-(hydroxymethyl)-L-gulono-1,4-lactone] (IPHMGL)84... 

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). 

Ethynyl compounds react with sugar lactones to give acetylenic lactols (16,63). Reaction of 2,3-O-isopropylidene-D-ribonolactone (16a) with lithium acetylenic derivatives gave l-(2-substituted ethynyl)-2,3-0-isopropyli-dene-D-ribofuranoses. Similarly, treatment of 2,3 5,6-di-O-isopropylidene-L-gulono-1,4-lactone (9b) with various lithium acetylenic reagents gave... 

A 500-mL, four-necked, reaction flask, equipped with a mechanical stirrer, thermometer, and glass pH electrode combined with an automatic titrator (Note 1), is charged with sodium (meta)periodate (85.5 g, 0.4 mol) (Note 2) and water (200 mL). The suspension is cooled to 0°C in an ice bath and 3 N sodium hydroxide (about 133 mL, 0.4 mol) is added dropwise at a rate such that the temperature does not exceed 7°C. The final pH of the suspension is 5.5. The cooling bath is removed and finely powdered 5,6-0-isopropylidene-L-gulono-1,4-lactone (Note 3) (43.6 g, 0.2 mol) Is added in one portion. The temperature of the mixture is kept below 30°C (Note 4). The pH of the suspension is maintained at 5.5 during the course of the reaction by addition of aqueous 15% sodium carbonate (about 15 mL). The suspension is further stirred at room temperature for 30 min, saturated with sodium chloride (105 g), and filtered by suction using a Buchner funnel. The white solid (Note 5) is washed thoroughly with two, 50-mL portions of brine and the pH of the combined aqueous layers is adjusted to... 

L-(S)-Glyceraldehyde acetonide 1,3-Dioxolane-4-carboxaldehyde, 2,2-dimethyl-, L- (8) 1,3-Dioxolane-4-carboxaldehyde, 2,2-dimethyl-, (S)- (9) (22323-80-4) Sodium (meta)periodate Periodic acid, sodium salt (8,9) (7790-28-5) 5,6-0-lsopropylidene-L-gulono-1,4-lactone L-Gulonic add, 5,6-0-(1-methylethylidene)-, y-lactone (11) (94697-68-4)... 

This enzyme [EC 1.1.1.20] catalyzes the reaction of l-gulono-1,4-lactone with NADP+ to produce D-glucur-ono-3,6-lactone and NADPH. 

Among them are found the naturally occurring 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ) [96]. Practical syntheses of DNJ and DMJ start from L-gulono-1,4-lactone (20b) and o-mannono-1,4-lactone (74), respectively [97]. Key intermediates are 2,6-dibromo-2,6-dideoxy-D-alditol derivatives 75a and 75b obtained by 2,6-dibromination of the starting lactones, followed by reduction with NaBH4 [98, 99]. Then a five-step sequence involving selective partial protection, introduction of an amine functionality, and intramolecular N-alkylation, lead to DNJ and DMJ, respectively (Scheme 22). 

The product analysis of L-ascorbic acid irradiated in deaerated solution is restricted to the measurement of dehydro-L-ascorbic acid, hydrogen, and the decrease in L-ascorbic acid.263 To account for the fact that N20 has no effect on G(L-ascorbic acid consumption), a rather complex mechanism has been put forward that also allows the formation of a reduction product (L-gulono-1,4-lactone, suggested but not measured). 

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. 

A formal synthesis of L-[6-3H]ascorbic acid was achieved when D-glucurono-6,3-lactone was reduced to L-[6-3H]gulono-l,4-lactone with sodium borotritide.354 L-Gulono-1,4-lactone has been converted into 1 by several routes (see Section III,7b,c). Starting with methyl o-xylo-2-hexulosonate, and following the method shown in Scheme 17, L-(5-2H)ascorbic acid was prepared by reduction of 121 with sodium boro-deuteride.547,548,587 In a related, but shorter, synthesis, sodium D-threo-2,5-hexodiulosonate was reduced with sodium borodeuteride to a mixture of keto-acids (see Section III,9d), which was esterified. By fractional recrystallization, methyl L-xylo-2-hexulosonate was obtained, and this was then converted598 into (5- H)l. 

Hydrogenation of L-ascorbic acid (Rh/C, H2) afforded L-gulono-1,4-lactone.57... 

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. 

D. S. Soriano, S. David, C. A. Meserole, and F. M. Mulcahy, Catalytic hydrogenation of L-ascorbic (vitamin C) a stereoselective process for the production of L-gulono-1,4-lactone,... 

---