Nitromethyl sugars

Reaction of the conventional 3-ulose prepared from di-O-isopropyl-idene-D-glucofuranose with nitromethane provided both the alio- and gluco- isomers of the corresponding 3-G-nitromethyl sugars, which were then converted by standard procedures to 3-C-hydroxymethyl pentoses with D-ribo, D-xylo, and D-lyxo configurations the last of these proved to be enantiomeric with the monosaccharide isolated from Phase I Coxiella burnetii LPS, which was confirmed by a synthesis of the L-form (16) from L-arabinose using the 3-ulose (17) with lithio 1, 3-dithiane to introduce the required L-lyxo branch chain. 

The 5-C-nitromethyl sugars mentioned above, obtained from D-glucose, have also been used to prepare validamine (38) and 5-epi-validamine (39), by use of a Michael addition of ammonia to the nitrocyclohexene intermediates (40) a related sequence yielded... 

Aldehydro-sugar derivatives, e.g, (49), have been chain extended using Seebach s silyl nitronate methodolo (Scheme 10) Unhindered nitromethyl-sugar... 

An improved synthesis of the 3-C-cyano branched-chain sugar 50 has been achieved by treating nitromethyl-sugar 51 under the Garegg and Samuelsson conditions (triphenylphosphine, imidazole and iodine) for the conversion of a vicinal diol to an alkene. ... 

Vasella has used deoxy-nitro sugars for the synthesis of various biologically important carbohydrates,10 and the radical nitromethylation of deoxy-nitro sugars has been used for synthesis of fructose 6-phosphate11 and 6-C-methyl and 6-C-(hydroxymethyl)analogues of V-acetylneuraminic acid (see Scheme 7.2).12... 

Consequently, the Michael addition reaction of sugar thiol proceeds smoothly with the formation of P- (l-2)-2,3-dideoxy-2-C-nitromethyl-thio-disacharides in 63-70 % yield (scheme 6). 

Addition of Pseudohalogens to Unsaturated Carbohydrates. Part III. Synthesis of 3-Deoxy-3-C-nitromethyl-D-allose, a Branched-chain Nitro Sugar, W. A. Szarek, J. S. Jewell, I. Szczerek, and J. K. N. Jones, Can.]. Chem., 47 (1969) 4473-4476. 

Because of their kinship to syntheses of nitro sugars, some syntheses of simpler, cyclic, aliphatic nitro compounds will be mentioned. Tetrahydropyran-2-ol, which is in tautomeric equilibrium with 5-hydroxypentanal (126), was found to undergo nitromethane addition catalyzed by sodium hydroxide to give120 tetrahydro-2-(nitromethyl)-pyran (128). Undoubtedly, the first reaction-product is the diol ni-tronate (127), which, under the conditions of processing (acidification and steam distillation), forms the cyclic ether 128. 

Introduction of a C-glycyl [—CH(NH2)C02H] side-chain has been accomplished in the case of the 3-ulose in Scheme 2, by either reaction with methyl 2-nitroacetate, followed by reduction and hydrolysis, or by reaction of the corresponding C-formyl derivative with sodium cyanide, ammonium carbonate, and carbon dioxide, followed by hydrolysis (Bucherer hydantoin procedure) (Scheme 4). A C-formyl side-chain can be established from a nitromethyl side-chain by oxidation of the sodium acinitronate salt by Ti chloride at pH 1. Several C-formyl branched-chain sugars have been synthesized in this way. ... 

The value of the 1,3-dithian route to branched-chain sugar derivatives has been illustrated further by stereospecific syntheses of 3-C-formyl, 3-C-hydroxymethyl, and 3-C-methyl derivatives of D-psicose from the ketone (373) via the dithianyl adduct (374). Addition of nitromethane to (373) gave both 3-C-nitromethyl-o-psicose and -fructose derivatives, which, after separation by chromatography, were reduced to the corresponding 3-C-aminomethyl derivatives. The use of dithianyl derivatives in the synthesis of streptomycin components is dealt with in Chapter 18. 

The facile conversion of C-nitromethyl- into aldehydo-groups with aqueous titanium (III) chloride has provided a convenient route to several C-formyl sugars, which can be isomerized to the thermodynamically favoured isomers with methan-olic sodium methoxide (Scheme 70). Conventional reactions have been used to obtain the 3-C-acetamidomethyl-3-deoxy-D-ribofuranose derivative (388) from l,2-0-isopropylidene-5-0-trityl-a-D-er> thro-pentofuranos-3-ulose, and the 6-benzoate (389) of 3-deoxy-l,2-0-isopropylidene-3-C-nitromethyl-a-D-allo-furanose has been converted, by a conventional chain-shortening procedure, into... 

The configuration of the branch point in branched-chain sugar derivatives (fi.g. methyl 2-benzamido-4,6-0-benzylidene-2-deoxy-3-C-nitromethyl-a-D-allo-pyranoside) has been assigned on the basis of the downfield chemical shifts obtained with Eu(fod)8, as compared with those of model compounds of known configuration. Chemical shifts and J values have been recorded for the 3,6-anhydro-sugar derivatives (507)—(509) in the presence, and in the absence. 

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