Gulono-l,4-lactones

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... 

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). 

Ogura and coworkers178,179 continued their study of the addition of lithiated heterocycles to 2,3 5,6-di-0-isopropylidene-L-gulono-l,4-lactone (50) and related compounds. In the case of the addition of lithiated 1,3-dithiane to 50, it was shown178 by X-ray crystal-structure analysis that l-(l,3-dithian-2-yl)-2,3 5,6-di-0-isopropylidene-/3-L-gulofuranose is R at the anomeric carbon atom. This demonstrates that the product of this reaction is, surprisingly, the more sterically hindered of the two products possible. This is the opposite of that predicted for addition of the lithiated dithiane from the less hindered side of 50 if no equilibration of the initial adduct is involved. 

O-lsopropylidene-L-gulono-l, 4-lactone was purchased from Fluka Chemical Corporation and used without any purification. It can also be synthesized from ascorbic acid in a two-step procedure.2... 

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. 

Furthermore, the sterically unfavorable, seven-membered lactams are readily obtainable from the 6-amino-6-deoxyaldonic acids. Thus, on treatment with alkali at room temperature, 6-amino-6-deoxy-L-gulono-l,4-lactone hydrochloride (157) gives L-gulono-l,6-lactam... 

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. 

When L-gulono-l,4-lactone (29) was treated with benzaldehyde diethyl acetal, ethyl 3,5 4,6-di-0-benzylidene-L-gulonate (32) was formed (49) in greater than 90% yield (Scheme 17). This derivative can be converted eflBciently into L-ascorbic acid by oxidation (> 90%) followed by hydrolysis of the resulting product to ethyl 2-keto-L-gulonate (L-x io-hexulosonate) (86%) and lactonization by either acid or base (90% ) to L-ascorbic acid. 

Di-O-isopropylidene-D-gulono-l,4-lactone, G-584 2,3 5,6-Di-O-isopropylidene-L-gulono-l,4-lactone, G-584 2,3 4,5-Di-0-isopropylidene-D-mannono-l,6-lactone, M-36 2,3 5,6-Di-0-isopropylidene-D-mannono-l,4-lactone, M-37 2,3 5,6-Di-0-isopropylidene-D-mannononitrile, M-36... 

The direct reaction of lithiated pyridine, imidazole, and benzothiazole, e/c., with 2,3 5,6-di-0-isopropylidene-L-gulono-l,4-lactone and 2,3-O-isopropylidene-D-ribono-1,4-lactone has been used to obtain analogues of C-nucleosides. ... 

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