Alditols and Derivatives

2-C-Methyl-D-erythritol 4-phosphate (4), a key isoprenoid precursor in the mevalonate-independent pathway leading to isopentenyl diphosphate, has been synthesized in eight steps from 1,2-0-isopropylidene-a-D-xylofuranose in such a way as to facilitate the incorporation of C or radiolabels. Syntheses of the non-phosphorylated derivative, 5, and its L-threitol diastereomer, 6, from d-glucose and D-galactose respectively, have also been reported. 3p-(5 -D-Ribityl)cholestane (7), a putative biological precursor for fossil 3-alkylsteranes, has been synthesized from cholestanone by the stepwise and stereoselective construction and subsequent reductive opening of a 3p-(5 -deoxy-5 -yl-D-ribono-l,4-lactone) substituent/ 

5-Deoxy-5-seleno-D-arabino-, D-ribo- and D-xylo-selenoformates 8, 9 and 10 have been prepared from D-arabinose and known 2,3,4-tri-O-benzyl-D-ribose and -D-xylose diethyl dithioacetals, respectively/ The thermolysis of these compounds to afford l,5-anhydro-5-deoxy-5-seleno-D-pentitols is covered in Chapter 11. 

The efficient reduction of unprotected 5-bromo-5-deoxy-D-ribono-, -D-ara-binono- and -D-xylono-1,4-lactones to the corresponding 1-bromo-l-deoxypen-titols using sodium borohydride in ethanol has been reported. Displacement of bromide by azide, either prior, or subsequent to the reduction, leads to the 1-azido-l-deoxy-L-ribo-, -D-lyxo- and -L-xylo-pentitols which can be further reduced to the 1-amino-1-deoxypentitols by hydrogenation.  

The Cr(VI) oxidation of o-glucitol and -mannitol has been studied. Oxidation occurred selectively at the primary hydroxyl groups to afford the corresponding 

Carbohydrate Chemistry, Volume 34 The Royal Society of Chemistry, 2003 

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Alditols and Derivatives Thereof.- 1,3 2,5 4,6-Trl-O-methylldene-D-mannltol,l-0-[bis(diethylamldo)thlonophosphate]-2,4 3,5-bis[0-(diethylamino)thlonophosphate]rlbltol, 1-amlno-l-deoxy-N-raethyl-... 

Neutral sugars, amino-sugars, alditols and derivatives thereof. - The h.p.l.c.-thennosinray m.s. of thirty monosaccharides and their derivatives has been reported. Trace levels of monosaccharides released by hydrolysis of glycosides from grape musts, and maniutol, 3-O-methyl-D-glucose and... 

It so happens that the great majority of compounds separated as acetates are alditols or other polyhydric compounds, and this Section is therefore concerned with the problems of reduction and acetylation. There is no a priori reason why alditols and other polyols should not be separated as their trimethylsilyl ethers, and such methods are known (see Section VII,l,p. 57 Section XIII, p. 90 Table Va, p. 119 and Table Xlla, p. 151), but experience shows that the resolution of acyclic O-trimethylsilyl derivatives is less satisfactory than that of cyclic compounds. 

The fact that each monosaccharide may give more than one peak owing to the formation of anomeric derivatives has led to a search for means to eliminate this complication. The anomeric center may be removed either by conversion into the oxime5 or the nitrile,394,3943 by oxidation followed by formation of the lactone (see Section IX, p. 71), or by reduction to the alditol. The last method is simpler than oxidation, and the separation of alditols and of aldononitriles will be discussed here additional examples are given in Table V (see p. 119). The early work on the separation of alditols has been discussed by Bishop.4 The necessity of decomposing borate complexes... 

Defaye19 called attention to the fact that the 2,5-anhydro-tri-0-(p-nitrobenzoyl)-D-lyxitol that he prepared is the enantiomorph of Barker and Fletcher s 1,4-anhydro-tri-0-(p-nitrobenzoyl)-L-arabinitol.l4alditol anhydrides derived, without Walden inversion, from two configurationally different sugars have been shown experimentally to possess the same, although enantiomorphic, configuration. 

With due consideration of the explanations just presented for the observed, relative stabilities of cyclic acetals derived from polyols, in terms of their constitution and conformation, nearly all of the following observations on the selective hydrolysis of cyclic acetals of alditols and dialkyl dithioacetals may be readily understood. 

Less is known concerning the partial, acid hydrolysis of alditol polyacetals derived from ketones, compared to those derived from aldehydes. The acid hydrolysis of 1,2 3,4 5,6-tri-O-isopropylidene-D-mannitol to 3,4-O-isopropylidene-D-mannitol55,56 and of l,2 3,4-di-0-isopropylidene-L-rhamnitol to 3,4-O-isopropylidene-L-rhamnitol57 indicates an order of isopropylidene acetal stability of a-threo > a, and this order is supported by the partial hydrolysis of 2,3 4,5-di-O-isopro-pylidene derivatives of dialkyl dithioacetals of D-arabinose58 and D-xylose59 to 2,3-acetals. 

Reduction of sugars into alditols is effected by treatment with sodium borohydride, and acetylation by treatment with acetic anhydride containing sulphuric acid (2%) at 80°C for 15 h [436] or for 4 h by refluxing with a mixture of acetic anhydride and pyridine (1 1) [437]. The excess of reducing agent is usually decomposed prior to the acylation by treatment with an acid. The boric acid so produced should be removed, as it forms a complex with alditols and retards the acylation. Polar stationary phases (e.g., Carbowax 20M), on which strong sorption and decomposition of the derivatives occur, are not very suitable for the GC separation of acetates. Carbowax 20M modified with terephthalic acid and XE-60 provides good results, but some derivatives do not separate. 

Peracetylated derivatives of alditols and reduced sugars are sufficiently stable for GC analysis and possessing good properties, but a relatively complicated procedure is required for their preparation. They also cannot be applied to the simultaneous determination of the sugar and the corresponding alditol with xylose, 2- and 4-substituted isomers cannot be resolved owing to the symmetry of xylitol. This gave rise to the use of combination with other derivatives, firstly with nitriles [442]. The procedure for a standard mixture... 

All monosaccharides and their derivatives that possess aldehyde or ketone groups (that is, excepting derivatives such as alditols and aldonic acids) will have reducing properties. Moreover, those with the appropriate number of carbon atoms can form rings occurring in two forms (anomers) and in which the potential reducing carbon is called the anomeric carbon. 

Aldoses, alditols and their derivatives are considered, including aza- and thiosugars (with nitrogen and sulfur in the pyranose or furanose rings). 

This review describes the synthetic approaches that have been developed since 2000 and summarizes the most important ones developed prior to 2000 [6,7,8,9,10]. It will concentrate on techniques generating enantiomerically enriched or pure carbohydrates and analogs. Aldoses, alditols, and their derivatives will be considered, including aza and thiosugars (with nitrogen and sulfur in the p)ranose or furanose rings). 

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