Nonulosonic acid preparation

In most structural studies of the polysaccharides, oligosaccharides containing the nonulosonic acids were prepared in order to have better-resolved NMR spectra and for investigation by MS. In some examples, a monosaccharide or a monosaccharide glycoside were also prepared by chemical degradations. 

A major improvement was realized with the use of indium, a metal with a very low first ionization potential (5.8 eV) which works without ultrasonic radiation even at room temperature [87]. As the zero-valent indium species is regenerated by either zinc, aluminum, or tin, a catalytic amount of indium trichloride together with zinc, aluminum [88], or tin [89] could be utilized in the allylation of carbonyl compounds in aqueous medium. The regeneration of indium after its use in an allylation process could be readily carried out by electrodeposition of the metal on an aluminum cathode [90], Compared with tin-mediated allylation in ethanol-water mixtures, the indium procedure is superior in terms of reactivity and selectivity. Indium-mediated allylation of pentoses and hexoses, which were however facilitated in dilute hydrochloric acid, produced fewer by-products and were more dia-stereoselective. The reactivity and the diastereoselectivity are compatible with a chelation-controlled reaction [84, 91]. Indeed, the methodology was used to prepare 3-deoxy-D-galacto-nonulosonic acid (KDN) [92, 93], N-acetylneuraminic acid [93, 94], and analogs [95],... 

Some deaminated Neu5Ac analogues were also prepared (rows 13-21), including 3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN, entry 13). 

However, the lack of stereochemical control at C-4 of newly created asymmetric center, resulting in the formation of two diastereomers, is the great disadvantage. Despite this, Comforth s methodology remains still the best choice for preparation of the selected ulosonic acids. It is a case of synthesis of nine stereoisomeric 5,7-diacetamido-3,5,7,9-tetradeoxy-2-nonulosonic acids [76]. The synthesis was performed by condensation of an appropriate 2,4-diacetamido-2,4,6-trideoxy-hexopiranoses with oxalacetic acid under basic conditions (Scheme 13), used previously in the preparation of Neu5Ac [77]. 

The stereochemical outcome of the hetero Diels-Alder reaction of the erythrose based diene with sodium glyoxylate was further rationalized by preparing the same compounds via decarboxylation of 2-carboethoxy-2-deoxy-2-ulosonic acid esters, obtained by cycloaddition with diethyl ketomalonate [146], A range of 2-nonulosonic acid derivatives - KDN analogues - were prepared including protected form of 2-deoxy-KDN,... 

As Neu5Ac aldolase accepts a range of substrates (more than 60 are known) in place of ManNAc, this enzyme can also used to synthesize Neu5Ac derivatives [149]. For example, if ManNAc is replaced by D-mannose, Neu5Ac aldolase can be used for the preparative-scale synthesis of KDN (3-deoxy-(5-D-g/ycer0-D-g /acto-2-nonulosonic acid Fig. 7) [150],... 

Branch at C-5 - The nonulosonic acid derivative 44 has been prepared by aldolase-catalysed reaction of pyruvate with 2-deoxy-2-C-hydroxymethyl-D-mannose as a possible synthon for the C-12 to C-20 sequence of amphotericin B. The latter compound was made in several steps from ethyl 2,3-dideoxy-4,5 6,7-di-0-isopropylidene-D-ara6/>io-hept-2-enoate by conjugate addition of vinylmagne-sium bromide followed by transformation of the vinyl group into a hydroxymethyl group in the key steps. ... 

NeuAc mediyl ester was prepared in quantitative yield by stirring NeuAc (1) in dry methanol with a catalytic amount of TFA. Upon complete removal of methanol, treatment of NeuAc methyl ester with l.OS equivalent of p-toluenesulfony chloride in pyridine at 0 provides 5-acetamido-9-tosyl-3,S,9-trideoxy-D-g(ycero-D-ga/oc/o-2-nonulosonic acid (2) in 76% yield. Complete convCTsirm of 2 to 9-azido-NeuAc (3) was achieved by reaction witii sodium azide in refluxing aqueous acetone, through simultaneous incorporation of the 9-azide and hydrolysis of the metlqrl ester (Scheme 1) in quantitative yield. Purification by column chromatogr q)hy gives the pure compound in 83% yield. 

Matrices containing neuraminic acid (5-acetamido-3,5-dideoxy-D-g/yceru-D-ga/acru-2-nonulosonic acid) residues have been prepared by reaction of 2-amino-ethylamides of the 2-hydroxyethyl, 2-aminoethylaminocarbonyImethyl, and 2-aminoethyl a-ketosides of the acid with agarose cyclic imidocarbonate to give... 

N-Glycosides (21) of 3-deoxy-D-g/ycero-D-ga/acto-2-nonulosonic acid (KDN) have been prepared. Use of a glycosyl acetate as donor towards silylated bases gave mixtures of a- and P-anomers, whilst the peracetylated p-glycosyl chloride and sodium salts of the pyrimidines gave just the a-nucleosides, albeit in modest yields. ... 

Human-liver /S-D-2-acetamido-2-deoxyhexosidase A was converted into a form exhibiting identical electrophoretic and immunological properties and thermostability to those of ]8-D-2-acetamido-2-deoxyhexosidase B on incubation with commercial culture filtrates of Vibrio cholerae, whereas purified preparations of neuraminidase had no effect. The factor responsible for the conversion was identified as merthiolate, a preservative added to commercial filtrates of V. cholerae. Thus, the conclusion that the A and B forms are glycoproteins containing different numbers of 5-acetamido-3,5-dideoxy-D- /ycero-D- a/ac/o-2-nonulosonic acid residues must be re-evaluated. 

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