Galactal 6-deoxy

Subsequently this route to 3-deoxy sugars was developed by further work in our laboratory by Ferrier and Sankey (23). They demonstrated that although tetra-O-acetyl-2-hydroxy-D-galactal undergoes rearrangement in boiling acetic acid, and that reaction is speeded up and goes to completion if catalytic amounts of methanesulfonic acid are added, the... 

From the rearrangement of tetra-O-acetyl-2-hydroxy-D-galactal in boiling acetic acid it was possible to isolate l,2,4,6-tetra-0-acetyl-2,3-dide-h.ydro-3-deoxy-a-jy-threo-hexose (32) (58%) and a small amount of 1,2,3,4,6-penta-O-acetyl-jS-D-galactopyranose. In the reaction mixture the presence of some a-pentaacetate was demonstrated chromatographically but NMR spectroscopy indicated no resonances corresponding to the / anomer of compound 32. These spectral measurements indicate that compound 32 constituted 80% of the mixture of products. 

Deoxy-2-[ F]fluoro-D-galactose can be prepared through an addition reaction to tri-O-acetyl-D-galactal (465), but better through Sn2 reaction (K F-Kryptofix 222 in MeCN) of methyl 3,4-0-isopropylidene-2-0-triflyl-6-0-trityl-y -D-talopyranoside (220 see Section 11,2), according to the cold synthesis. 

Nitroglycals65 are excellent Michael-type acceptors,66 where O-, N-, S-, C- and P-nucleophiles can be used as donors.67 An application of this kind of reaction was reported by Schmidt et al. for a new synthesis of 2-deoxy-2-nitro-D-galactose nucleoside 86 and of /V-acetyl-D-galactosamine nucleoside 88, based on addition reactions to 3,4,6-tri-0-benzyl-2-nitro-D-galactal 85 (Scheme 28).68... 

Unsaturated sugars, namely glycals, such as 3,4,6-tri-Oacetyl-l, 5-anhydro-2-dcoxy-D-r//v/-/w7o-hex-1-enetol and the d-/v.yo epimer react with xenon difluoride in the presence of a boron trifluoride-diethyl ether complex to give a mixture of C2 epimeric fluorides.45,46 Tri-O-acctyl-D-galactal treated with xenon difluoride in trichlorofluoromcthane below 5 C forms after hydrolysis (0.5 M HC1) 2-deoxy-2-fluoro-D-galactose in 63% overall yield.47... 

The hexosylulose derivative 7c may also be converted into the GDP derivative of colitose (3,6-dideoxy-L-xy/o-hexose, 3,6-dideoxy- L-galact-ose ),161,195 a component of lipopolysaccharides from several enterobacterial strains. Another monosaccharide of this group, ascarylose (3,6-dideoxy-L-arabino-hexose, 3,6-dideoxy- L-mannose ), which is present in Yersinia pseudotuberculosis lipopolysaccharides, was found to be synthesized as the CDP derivative through epimerization and reduction of CDP-6-deoxy-D-xy/o-hexos-4-ulose.168 171... 

Simple alkylation can be accomplished by use of trialkylaluminums which, with Lewis acids, afford 1-C-alkyl products such as 90, available in 72% yield by reaction between di-O-acetyl-6-deoxy-D-galactal and trimethylaluminum in the presence of titanium tetrachloride in dichloro-methane at —78 °C.109 Importantly, the reaction can also be applied to 1-alkylglycals, also with high stereoselectivity, so that the doubly substituted compound 91 can, for example, be made by allylation of tri-O-acetyl-l-C-methyl-D-glucal. Its C-l epimer is available by C-methylation of the 1-C-allylglucal.110... 

Glycals with C-2 substituents that have unsaturated, electron-withdrawing character undergo nucleophilic addition at C-l and are therefore potential glycosylating agents. The use of tri-O-benzyl-2-nitro-D-galactal in the synthesis of 2-amino-2-deoxy-a- and /1-galactosides by this approach has already been mentioned (Section II.2.a.i). 

Korytnyk and coworkers have shown that reactions of xenon difluoride with acetylated glycals in the presence of boron trifluoride are a convenient route for the synthesis of 1,2-difluoro sugars, while the addition of fluorine to the double bond occurred predominantly from the less hindered side and cis adducts were mainly formed75, 76. Stereoselective transformation of tri-O-acetyl-D-galactal with xenon difluoride at -20 to +5 °C, without a catalyst in CFC13, after hydrolysis, afforded 2-deoxy-2-fluoro-D-galactose in 63% yield77. 

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