Gulono-1, reduction

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-... 

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. 

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%). 

A variety of methods has been developed for the reduction of the gulonolactones and derivatives to D- and L-gulose and the corresponding derivatives. D-Gulono-1,4-lactone (2) was reduced to D-gulose (d-... 

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. 

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. 

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). 

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. 

Another method for converting D-glucuronolactone (27) into L-ascorbic acid is shown in Scheme 16 (49). When L-gulono-1,4-lactone (29), which is readily available by the reduction of 27, is treated with benz-aldehyde, 3,5-0-benzylidene-L-gulono-l,4-lactone (30) is formed. 

Full details of the synthesis of S-amino-S-deoxy-D-gluconolactam and 1-deoxynojirimycin (Vol.27, p.206) have been published, and the method, which involved reduction of a S-keto-aldonamide, has been applied to the synthesis of S-amino-S-deoxy-o-galactonolactam, 4-amino-4-deoxy-D-arabinonolactam, and a mixture of S-amino-5-deoxy-D-mannono- and L-gulono-lactams. Syntheses of a-azido-C-formyl branched-chain sugars are covered in Chapters 14 and 24. 

Acid Derivatives.— 2,2 5,6-Di-0-isopropylidene-2-C-hydroxymethyl-L-gulono-1,4-lactone/ AT-(2-chloroethyl)-D-gluconamide (n.d.)/ 5-azido-5-deoxy-AriV-diethyl-l,2-0-isopropylidene-3-(9-methanesulphonyl-P-L-iodoruranuron-amide/ 3,6-anhydro-7-(4-bromobenzoyl)-2-deoxy-4,5-0-isopropylidene-D-ahro-heptononitrile/ sodium o-isoascorbate, and reductic acid (2,3-di-hydroxycycIopent-2-enone). . 

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