Hexuronic acids derivatives

An entirely different approach to pyranoid 4-enes depends on eliminations from 5-bromo compounds obtained from pyranoid hexuronic acid derivatives by photobromination. Treated with zinc-acetic acid, the bromide 249 gives the glycal -like 250 (62%), while the 4-acetoxy compound 251 is formed when DBU is used to promote elimination. Similarly, base treatment of penta-0-acetyl-5-bromo-/J-D-glucose with DBU causes the analogous loss of hydrogen bromide and formation of the 4-acetoxy-4-ene, but use of zinc-acetic acid affords mainly the 5-exo-methylene alkene by the alternative available elimination process.237... 

At the time of writing of the earlier article,1 compounds in this class had been prepared only from hexuronic acid derivatives by base- or enzyme-catalyzed eliminations methyl (methyl 4-deoxy-/3-L-threo-hex-4-enopyranosid)uronate (73), for example, had been pre-... 

Methods for the regioselective radical-mediated bromination of carbohydrates have been reviewed by Somsak and Perrier [95]. Photobromination of hexuronic acid derivatives with non-activating anomeric substituents leads preferentially to formation of the C-5 brominated product via the stabilized captodative radical at C-5. 

Hetero-Diels-Alder reactions have been used in the construction of amino-sugars, asymmetry being induced by the use of either a chiral Lewis acid catalyst or a chiral auxiliary. Thus, the 3-amino-hexuronic acid derivatives 61 were obtained with high de and ee using a copper(II) triflate catalyst with a chiral bisoxazoline ligand. 4-Amino-4-deoxy-D-erythrose and 4-amino-4,5-dideoxy-L-lyxose (63), the latter a potent inhibitor of a-L-fucosidase, were obtained from the D-pyroglutamic add-containing diene 62 (Scheme 19). ... 

Auvray X., Labulle B., Petipas C., Bertho J.-N., Benvegnu T, Plusquellec D., Thermotropic liquid-crystalline properties of some novel hexuronic acid derivatives bearing a single or two alkyl chains, J. Mater. Chem., 7(8), 1997, 1373-1376. 

A novel 4-W-aroylated 4-amino-2,3,4,6-tetradeoxy-3-dimethylamino-P-(yjto-hexopyranoside unit of unknown absolute stereochemistry has been identified as a constituent residue of a new macrolide antibiotic. Syntheses of neamine derivatives IV-acylated with amino acid residues are covered in Chapter 18. Racemic 3-deoxy-prumicin (79), which is still active as an antibiotic, was synthesized from furfuryl alcohol (78) (Scheme 20), the 4-amino-group being introduced by sulphonate displacement with azide ion. A variety of six and seven carbon analogues (81) of 6-acetamido-2,6-dideoxyneuraminic acid have been synthesized from 2-amino-2-deoxy-D-glucose via the 4-deoxy-hexuronic acid derivative (80) (Scheme 21). It was evident from their weak sialidase inhibitory properties that the intact carbon chain is required for good binding. ... 

In addition to oligomers obtained from the amino-acid (114), two other reports have described the synthesis of disaccharides linked through amide bonds. Hexosaminides (e.g. benzyl 2-amino-2-deoxy-a-D-glucopyranoside) have been condensed directly, or in the presence of DCC, with hexuronic acid derivatives (e.g. l,2 3,4-di-0-isopropylidene-a-D-galactopyranosyluronic acid) to give the corresponding A -acylamino derivatives [e.g. (128)], and a similar... 

The g.l.c. of TMS ethers of hexuronic acid derivatives is referred to in Chapter 26. 

The condensation of hexuronic acid derivatives with hexosaminides to give amide-linked disaccharides is referred to in Chapter D-Galacturonic acid has been identified as a component of Pneumococcus type 25 capsular polysaccharide," and 2-O-methyl-D-glucuronic acid has been isolated for the first time in Nature from an extracellular polysaccharide of a species (Porphyridium cruentum) of red alga. The acidic sugar component in Klebsiella type 37 capsular polysaccharide has been identified as 4-0-[(5)-l-carboxyethyl]-D-glucuronic acid. Antibiotic substances and nucleosides that contain uronic acid components are referred to in Chapters 20 and 21, respectively. 

Structural Identification of Isomeric O-Trimethylsilyl Derivatives of Some Hexuronic Acids, J. F. Kennedy, S. M. Robertson, and M. Stacey, Carbohydr. Res., 57 (1977) 205-214. 

The three acid-derived components of the hexuronic acids, namely, 5, 47, and 48, are essentially end products in the reaction. This is quite surprising, as 48 required only decarboxylation to form 2-furaldehyde. However, the rate of decarboxylation of the furoic acid was <2% of that of D-galacturonic acid under similar conditions. Furthermore, no trace of pentoses was noted in any of the reaction mixtures, which eliminates previous suggestions of their role in the mechanism of 2-furaldehyde for-... 

Scheme 32 ALkylidene derivatives of hexuronic acid 6,3-lactone...

In model experiments,205 it was found that concentration of an aqueous solution of the aldonic acids in the presence of hydrochloric acid gives exclusively the 1,4-lactones, which, on subsequent trimethyl-silylation, give only one peak on the chromatogram. This method was successfully employed for the separation of D-galacturonic, D-glucuronic, and D-mannuronic acids. Of the 1,4-lactones examined, only the trimethylsilyl ether of D-mannono-1,4-lactone was obtained in crystalline form. However, all of the derivatives showed characteristic differences in their infrared spectra in the range of 1500 to 600 cm"1. When this method was applied to the determination of uronic acids in a variety of polysaccharides,205 it was impossible to find any hydrolytic conditions under which the uronic acids were quantitatively released and then reduced, a problem experienced by other workers.20 The method was, however, successful in affording a qualitative, microscale procedure for the identification of hexuronic acids (which otherwise are difficult to detect). 

In concentrated sulfuric acid, D-glucuronic acid is dehydrated more slowly than either its 4-O-methyl derivative or D-glucose, probably because of the stability of its lactone. All hexuronic acids, however, eventually produce the same characteristic absorbance that corresponds roughly to a composite of 5-formyl-2-furoic acid, 2-furaldehyde, and reductic acid. It is interesting that a thin-layer chromatographic examination of the reaction products of D-glucuronic acid with 89% sulfuric acid at 70° revealed 5-formyl-2-furoic acid as a major product, but no evidence was obtained for the presence of reductic acid. This result is in distinct contrast to the products obtained in dilute acid solutions, in which 5-formyl-2-furoic acid is produced in very low yield, whereas reductic acid is formed in yields in excess of 10%. 

The fourth student in this group, Stanford Moore, began his doctoral thesis research with Link in 1935. His work involved the development of a new, and still useful, procedure for oxidizing aldoses to the aldonic acids by potassium hypoiodite in methanol solution the resulting aldonic acids were then converted into nicely crystalline benzimidazole derivatives that proved more suitable for the characterization of carbohydrates than the classical osazones. This method, developed by Moore and Link (1940), was extended to the characterization of hexuronic acids, as their bis(benzimidazole)s, after oxidation to the glycaric acid (R. Lohmar, Dimler, Moore, and Link, 1942), of lactic acid (Moore, Dimler, and Link, 1941 Dimler and Link, 1942), and of ribose, fucose, and digitoxose (Dimler and Link, 1943). During these... 

The following Tables (II, III, and IV) record appropriate data and references relating to the methyl ethers of some hexuronic acids and their derivatives. In the case of methyl ethers of aldobiouronic acids (Table V), data have been recorded only for crystalline derivatives. Where uronic acids have been characterized by reduction to the corresponding hexose, reference should be made to the previous articles in this series dealing with the methyl ethers of D-glucose,71 D-galactose,72 and D-mannose.73... 

Disaccharides of the hexuronic acid-hexosamine type constitute the fundamental repeating unit of many mucopolysaccharides, from which they are derived by hydrolytic degradation. Further hydrolytic treatment results generally in destruction of the uronic acid moiety of the disaccharide. Structural studies have been made on the disaccharides from hyaluronic acid (hyalobiouronic acid), chondroitinsulfate (chondrosine), and heparin (heparosine). 

Use of 1-14C has shown that the methyl group is derived from C-l of hexuronic acid or pentose.54 If prepared in D20, NMR shows hydrogen exchange from both C-2 and CH3. This accords with CH2 C(OH)... intermediates (on the 2,3-enolisation route). 

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