Unprotected aldoses

It is possible to combine both the type I and the type II situations in the coupling of a chiral aldehyde with a substituted allylic halide. Such is the case in the coupling of unprotected aldoses (e.g., glyceraldehyde)... 

A new synthetic route for functionalized polyhydroxyalkyl-pyrimidines starting from unprotected aldoses and based on montmorillonite K-10 catalysis and solvent-free microwave irradiation conditions, has been reported by Yadav et al,m Thus, reaction of D-glucose and D-xylose with semicarbazide or thiosemicarbazide (186) in the presence of montmorillonite K-10, under microwave irradiation, proceeded via domino cycloisomerization, dehydrazination, and dehydration of the intermediate semi- or thiosemicarbazones (187) to afford l,3-oxazin-2-ones or l,3-oxazine-2-thiones (188) in one single step and in yields between 79% and 85% (Scheme 34). Other mineral catalysts tested, such as silica gel and basic alumina, were far less effective for this transformation and only silica gel was active at all, giving low yields (15-28%) of compounds 188a-d. The l,3-oxazin-2-ones(thiones) thus synthesized were subsequently converted into the target pyrimidines by reaction with aromatic... 

SCHEME 34. Synthesis of l,3-oxazin-2-ones and 1,3-0xazin-2-thiones from unprotected aldoses... 

Aldonolactones are commercially available at low cost, when compared to most of the common monosaccharides. They are typically synthesized by selective anomeric oxidation of unprotected aldoses with bromine [6]. Usually the thermodynamically more stable five-membered lactone (y-lactone) predominates over the six-membered form, with the exception of o-gluconolactone, which crystallizes as the 1,5-pyranolactone (5-lactone) [7] (Scheme 1). Another method for the preparation of sugar lactones is the dehydrogenation of unprotected or partially... 

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

Unprotected aldoses can be selectively oxidized at the anomeric center to afford aldonic acids/aldonolactones. This oxidation can be achieved by chemical as well as by biochemical... 

Unprotected aldoses and ketoses can be reduced to afford alditols while aldonolactones can be reduced to give either aldoses or alditols. The reagent of choice for reduction to alditols is sodium borohydride since it is both cheap and convenient to use. The reduction is carried out under mild conditions at room temperature in an aqueous solution. Sodium borohydride is stable in water at pH 14 while it reacts with the solvent at neutral or slightly acidic pH, but at a slower rate than the rate of carbonyl reduction. In some cases, the product will form esters with the generated boric acid. These borate complexes can be decomposed by treatment with hydrochloric acid or a strongly acidic ion-exchange resin and the boric acid can be removed in the work-up as the low boiling trimethyl borate by repeated co-evaporation with methanol at acidic pH [155]. 

One of the best methods developed by Whitesides et al. was an indium mediated direct nucleophilic addition of ethyl 2-(bromomethyl)acrylate to unprotected aldoses in aqueous media [111] (Scheme 36). An other advantage of this reaction is that it can be compatible with a variety of functional groups [111,112], The resulting allyl-compounds were produced in good yield. Ozonolysis, then cyclization of the resulting ketones afforded the corresponding ulosonic acids. 

In a useful variant of the Wittig olefination process, unprotected aldoses reacted in dioxane at around reflux temperature with stabilized ylides of the type Ph3P=CHC02R, where R is a bulky substituent (Bu , CHPhz), giving high yields of acyclic products with -selectivity. No cyclic products resulting from intramolecular Michael reaction were formed. ... 

D-lincosaminide (22) starting from aldehyde 21, prepared in 6 steps fiom D-threonine and furanyl lithium is outlined in Scheme 8. Several unprotected aldoses (D-glucose, D-galactose, D-arabinose,... 

Unprotected Aldoses Terminal Alkynes MS 5A, dioxane, rt, 72 h 21 examples... 

Anomeric O-Alkylation of Unprotected Aldoses with Primary Triflate, Bromides, and Cyclic Sulfates... 

We can also use 0-unprotected aldoses for anomeric 0-alkylation by employing an aprotic dipolar solvent, namely A, A -dimethylhexahydropyrimidin-2-one (DMPU) [17]. DMPU is essential to accomplish the anomeric O-decylation of O-... 

AUylation of unprotected aldoses in aqueous media has previously been carried out with allyl bromide and tin (see Vol. 25, Chapter 2, Ref. 31). This method has now been improved by replacement of tin with indium, and extended to substituted allylic Inomides. Its usefiilness is impressively demonstrated by the conversion of 2-acetamido-2-deoxy-D-inannose to neuraminic add derivative 42 in 3 steps and 45% overall yield, as shown in Scheme 7. ... 

By a one-pot, operationally simple cascade reaction of isocyanides with unprotected aldoses and amino acids, an access to a broad range of defined glycosylated pseudopeptides is given. 

Bauman and Axendale [12] reported a new approach to synthesized functionalized thioimidazoles via three-component reaction using unprotected aldoses and ketoses. This sequential approach is based on the Marckwald reaction as illustrated in Scheme 6.8. 

SCHEME 6.8 Synthesis of functionalized thioimidazoles via three-component reaction using unprotected aldoses and ketoses. 

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