Gulono-1, preparation

The major pathway probably proceeds via D-galacturonic acid and L-galactono-1,4-lactone, as these are converted to L-ascorbic acid by mitochondria prepared from peas and mung beans, but neither L-gulono-1,4-... 

It has also been reported that D-galactose can be isomerized with molybdic acid to a mixture containing D-talose and D-gulose, but the yields are low.34-35 A number of derivatives of gulono-1,4-lactone have been prepared that, by reduction, would provide selectively protected derivatives of gulose. These derivatives will be discussed in subsequent Sections of this article. 

Several amides of derivatives of L-gulonic acid (3) have been prepared. On treatment of 2,3 5,6-di-O-isopropylidene-L-gulono-l,4-lactone (the preparation of which is discussed in Section V) with ammonia in methanol, 2,3 5,6-di-0-isopropylidene-L-gulonamide (45) is formed.76 Similarly, 3,5-O-benzylidene-L-gulonamide (46) was prepared76 from the corresponding lactone. 

Several, fully protected derivatives of gulonolactone have been prepared these include 2,3,5,6-tetra-0-(trimethylsilyl)-D-gulono-l,4-lactone (55, R = SiMe3),51 2,3,5,6-tetra-0-acetyl-D-gulono-l,4-lactone (55, R = acetyl),88,89 2,3,5,6-tetra-0-benzoyl-D-gulono-l,4-lactone90,91 (55, R = benzoyl), and l-55 (R = benzoyl).91,92... 

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... 

A variety of miscellaneous derivatives of gulonolactone has been reported. Linn treated D-glucofuranurono-6,3-lactone (7) with chlorobenzene and aluminum trichloride in order to obtain115 6-deoxy-6,6-diphenyl-L-gulonic acid (70). Various related compounds were also prepared. When 7 was treated with sulfur dioxide and 2-(isonicotin-oyl)hydrazine in water, 6-deoxy-6-(2-isonicotinoylhydrazino)-6-sulfo-D-gulono-1,4-lactone (71) was formed in 81% yield.116,117 Kawabata... 

Finally, when L-sorbose (81) was treated with hydrogen cyanide, a branched-chain, sugar lactone was formed which was characterized by converting it into a diacetal.127 An X-ray structure determination of this material revealed it to be 2,21 5,6-di-0-isopropylidene-[2-C-(hy-droxymethyl)-L-gulono-l,4-lactone] (82). However, all subsequent efforts to prepare 82 resulted in the formation of 2,3 5,6-di-0-isopropyli-dene-2-C-(hydroxymethyl)-L-gulono-l,4-lactone (83). 

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. 

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). 

Butenolides have also been prepared from aldohexono-1,4-lactones via trimethylammonium methylidene derivatives (15). 5,6-0-Isopropylidene-L-gulono- (9a) and D-mannono-1,4-lactone (10a) were converted into 2-(di-methylamino)-l,3-dioxolane derivatives, which on treatment with iodomethane followed by thermal decomposition yielded compounds 226 and 227 respectively. 

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. 

The key butenolide needed by Buszek, for his synthesis of (—)-octalactin A, had already been prepared by Godefroi and Chittenden and coworkers some years earlier (Scheme 13.4).9 Their pathway to 10 provides it in excellent overall yield, in three straightforward steps from l-ascorbic acid. The first step entails stereospecific hydrogenation of the double bond to obtain L-gulono-1,4-lactone 13. Reduction occurs exclusively from the sterically less-encumbered ot face of the alkene in this reaction. Tetraol 13 was then converted to the 2,6-dibromide 14 with HBr and acetic anhydride in acetic acid. Selective dehalogenation of 14 with sodium bisulfite finally procured 10. It is likely that the electron-withdrawing effect of the carbonyl in 14 preferentially weakens the adjacent C—Br bond, making this halide more susceptible to reductive elimination under these reaction conditions. 

Preparation. 6-Deoxy-D-gulose was originally prepared by the cyanohydrin synthesis from 5-deoxy-D-xylose. A simple preparation of 6-deoxy-D-gulose from D-gulono-1,4-lactone has been described.172... 

Several unsaturated aldonlc acid derivatives have been reported. The enantiomeric 2,3-dideoxy analogues (7) of ascorbic acid have been prepared from 5,6-0 -isopropylidene-L-gulono- and D-mannono-1, -lactones by formation of their 2-(dimethylamino)-l,3-dioxolane... 

---