Gulono- 1,4-lactone synthesis

Vitamin A could control differentiation by decreasing enzyme activities, by stimulating enzyme synthesis, or both. The activity of a number of enzymes (gulono-lactone oxidase, codeine demethylase, squalene cyclo-dehydrase, ATP-sulfurylase, and sulfate transferase) decreases in vitamin A-deficient animals. The significance of these observations remains obscure, and no specific coenzymic role for vitamin A has as yet been discovered. 

The following article summarizes the methods of synthesis for L-gu-lono-1,4-lactone (1), D-gulono-1,4-lactone (2), and the corresponding... 

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-... 

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. 

Aldonolactones are useful starting materials for the synthesis of modified sugars. They have also been used as chiral templates in synthesis of natural products. Some of them are inexpensive, commercially available products or they may be obtained readily from the respective monosaccharides. The purpose of this chapter is to survey the main reactions of aldonolactones. Previous reviews on the subject include articles on gulono-1,4-lactones (1) and D-ribonolactone (2). Methods of synthesis, conformational analysis, and biological properties are not discussed in this chapter. 

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. 

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. 

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). 

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... 

The nitrone 266 bearing a D-gulono-y-lactone auxiliary directs addition of methylmagnesium bromide as a key step in synthesis of (/7)-zilegton (Scheme 54). The gulonic-acid derived auxiliary 267 has been described as an improvement on a previously reported carbohydrate oxazolidinone auxilary (see Chapter 10)... 

Koshizaka, T, Nishikimi, M., Tanaka, M., Nakashima, K., Ozawa, T., and Yagi, K., 1987, In vitro synthesis of L-gulono-7-lactone oxidase by rabbit reticulocyte lysate, Biochem. Int. 15 779-783. 

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