Ulosonic acid

The ulosonic acid derivative 15 has been isolated from the marine sponge Mycale mytilorum however, the stereochemistry has yet to be determined.  

A one- and two-dimensional NMR study of the acetic acid-induced lactoniz-ation of a-iV-acetylneuraminyl-(2- 3)-lactose showed that the major product 17 involved cyclization to 0-2 of the galactose unit, while a minor lactone involved 0-6 of this moiety.  

An enantioselective synthesis of 18 was achieved. This is a deoxy analogue of naturally occurring 3-deoxy-D-gf/yccro-D-firu/acm-2-non-2-ulosonic acid (KDN).  

2-Ulosonic acids can be produced in high yield by oxidation of 

In related work the derivative (13) of 3-deoxy-L-gulo-oct-2-ulosonlc acid was synthesized from 5,6-anhydro-l,3 2,4-di-0 -ethyl-idene-D-glucitol and the anion of ethyl 1,3-dithlane-2-carboxylate. 

An Improvement in the Cornforth procedure for making KDO (3-deoxy-D-manno-oct-2-ulosonlc acid) has been reported together 

Analogues of KDO have been made by condensation between pentoses or modified pentoses and oxalacetic acid. 5-Deoxy-D-arabinose gave 3.8-dldeoxy-D-manno-oct-2-ulosonlc acid (8-deoxy-KDO). 

Various mono- and ollgo-saccharide derivatives of KDO have been subjected to methylation, reduction and acetylation treatment to afford compounds suitable for mass spectrometric analysis. Rules for fragmentation of the 3-deoxyoctltol derivatives were 

A route to hept-2-ulosonic acid derivatives is available by way of the reaction of 2,3 4,5-di-0-isopropylidene-L-arabinose and 2,4 3,5-di-0-ethylidene-L-xylose with ethyl nitrosoacetate. ° Isomerization of the intermediate nitroso derivatives with alcoholic sodium nitrite yielded the corresponding oximes, which can be deoximated with lead tetra-acetate in acetic acid. 3-Deoxy-D-manno-oct-2-ulosonic acid 5-(dihydrogen phosphate) and its D-gluco analogue have been obtained by base-catalysed condensation of o-arabinose 2-phosphate (obtained by way of phosphorylation of benzyl 3,4-0-isopropylidene-P-D-arabinopyrano-side) with oxalacetic and separation of the isomers by ion-exchange chromato-graphy.  

The efficiency of the oxidation of 2,3 4,6-di-O-isopropylidene-a-L-sorbofuranose to 2,3 4,6-di-0-isopropylidene-a-L-arafciMo-hexulopyranosonic acid (a stage in the manufacture of L-ascorbic acid) with sodium hypochlorite and nickel sulphate (as a catalyst) has been shown to depend on the characteristics of the catalyst, the temperature of the reaction, and the concentration of the reactants. The catalytic activities of a number of metal cations e.g. Cu , Ag , Co, Fe , and Ce ) in the electrochemical oxidation of 2,3 4,6-di-0-isopropylidene-a-L-sorbofuranose have also been examined, but none were as effective as Ni cations.  

3-Deoxy-D-g/yce/ u-pentulosonic acid 5-phosphate has been obtained both by oxidation of a mixture of 3 -dto y-D-erythro and -D-t/rreu-pentonic acid 5-phosphates with potassium chlorate-vanadium(v) oxide and by treatment of a mixture 

L-xy/o-Hexulosonic acid has been prepared via oxidation of 3,4 5,6-di-0-iso-propylidene-L-sorbose and the racemic derivative (296) was produced on thermolysis of the ozonide (27) (see Chapter 3). 3-Deoxy-D-uw6i/io-[l- C]heptulosonic acid 7-phosphate has been synthesized by addition of potassium [ C]cyanide to 2-deoxy-D-ara6i o-hexose 6-phosphate, hydrolysis, and selective oxidation of the resulting 3-deoxyheptonic acid 7-phosphates at C-2 with potassium chlorate-vanadium(v) oxide. A one-step synthesis of a mixture of 3-deoxy-D-r/6o- and -D-araWno-heptulosonic acid 7-phosphates is based on a metal-ion-catalysed reaction of o-erythrose 4-phosphate with oxalacetate.  

Gospodinov, Sh. Levi, E. Pencheva, and P. Lazarova, Trudy Nauchroizsled. Khim.-Farm. 

3-Deoxy-D-mfmw-octulosonic acid has been identified as the principal component (53%) of the capsular polysaccharide antigen of Neisseria meningitidis serogroup 29-e.  

The isomeric forms of hexulosonic acids present in aqueous and other solutions have been studied by C n.m.r. methods. L-xy/o-Hexulosonic acid and its methyl ester exist predominantly in the a-pyranose form, whereas the D-arabino-isomers show a- and j3-pyranose and ot- and /3-furanose forms. The methyl ester favours the pyranoses in water and the furanoses in DMSO. D-xy/o-Hex-5-ulosonic acid showed both furanoses and the acyclic form, while this latter 

de Pascual Teresa, J. C. Hernindez Aubanell, A. San Feliciano, and J. M. Miguel del Corral, Tetrahedron Lett., 1980,21,1359. 

Continuing his work on 3-deoxyald-2-ulosonic acids Szabo has shown that 

2- O-benzyl-D-glyceraldehyde condensed with oxaloacetic acid gives 5-O-benzyl- 

Pesheva, A. Shterev, Kh. Chapkunov, M. Dolapchieva, B. Asenov, and D. Merdzhanova, Tr. Nauchnoizsled. Khim. -Farm. Inst., 1978,10,95 Chem. Abstr., 1980, 93,175954). 

Oxidation of 2,3 4,6-di-0-isopropylidene-L-sorbose to the 2-ulosonic acid analogue can be effected using chromium trioxide and celite with the alcohol in ether-dichloromethane. ° 

Acylation of methyl 3-deoxy-D-mflnno-oct-2-ulosonate leads to furanose derivatives, e.g. (15), while similar treatment of the free acid or its ammonium salt affords pyranoid products. Methanolysis of the ester gives mixed 5-membered 

In the area of 3-ulosonic acids, the pentose derivative (17) has been prepared from 2,3-O-isopropylidene-D-glyceraldehyde by use of diazoacetic ester,and 

The enolization of the diketo-acid D-t)jreo-hex-2,3-diulosonic acid has been studied as a function of pH, and the structure of sodium u-threo- icx-2,5-diulosonate has been shown by X-ray and n.m.r. methods to be the hydrate a-pyranoid form (22).  

A review on the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics features the use of aldolases in the synthesis of neuraminic acid and KDO analogues.  

The application of indium- and tin-mediated Barbier-Grignard reactions in aqueous solution to the chain extension of unprotected sugars has been reviewed. Some C-5 variants of iV-acetylneuraminic acid have been prepared by the indium-mediated addition of ethyl oc-(bromomethyl)acrylate to variously N-substituted mannosamines, and similar chemistry using (bromomethyl)vinyl phosphonate has led to the phosphonate analogue 12. The reaction of O-protected aldono-1,4- and -1,5-lactones with (2-bromomethyl)-acrylate or -acrylonitrile or 2-bromobutyrolactone mediated by samarium diodide led to chain-extended ulosonic acid derivatives.  

3-Deoxy-D-/Areo-hex-2-ulosonic acid has been synthesized by way of a Lewis acid catalysed ene reaction between methyl glyoxalate and l-/er/-butyldiphenylsi-lyloxy-but-3-ene.  

A new 8-step synthesis of the neuraminidase inhibitor 19 from neuraminic acid has been outlined, and a number of analogues 18 with modified substituents on N-5, as well as a 6-thio-analogue, have been prepared and evaluated as neuraminidase inhibitors. The carboxamides 20 and 21 have also been synthe- 

A large number of aldoses and derivatives have been tested as substrates for NeuSAc aldolase which adds pyruvic acid to the aldose. A free hydroxyl group is required at C-3 of the aldose, and aldoses with the -configuration at C-3 lead to products with the iS-configuration at C-4 in the product. An enzymic method for the conversion of /V-acetyl-D-mannosamine and D-mannose into neuraminic acid and Kdo respectively has been improved and simplified, and the reactions were carried out on a 10 g scale. iV-Acetyl-4-azido-4-deoxy-D-mannosaniine has been converted with an aldolase into 5-acetamido-7-azido-3,5,7-trideoxy-D-g/ycero-D-gfl/flcro-2-nonulopyranosonicacid.  

Sequential aldol trimerisation of acetaldehyde catalysed by aldolases followed by enzymic addition of pyruvic acid has afforded the tetradeoxy-nonulopyrano-sonic acid 26, and the preparation of some 3-deoxy-octulosonic acids and 3-deoxy-heptulosonic acids is discussed in Chapter 2. 

A synthesis of 3-deoxy- D-glycero-D-galacto-2-nonu osonic acid from d-mannose involved use of a keto-thiazole Wittig reagent,while addition of lithiated thiazole to a 2-deoxy-hexono-1,4-lactone featured in a synthesis of 3-deoxy-D-ara )j io-hept-2-ulosonic acid. 

In a further example of indium-mediated additions to aldoses, a-(bromo-methyl)acrylic acid added to A-acetylmannosamine in the presence of indium to give branched derivative 27 and its C-4 epimer. Ozonolysis of 27 afforded N-acetylneuraminic acid. In a study of the oxidation of L-sorbose (5% Pt/AlaOa, O2) to 2-keto-L-gulonic acid it was found that the reaction rate and selectivity was improved in the presence of certain tertiary amines. The synthesis of a carbocyclic analogue of iV-acetyl-neuraminic acid is discussed in Chapter 18. 

A synthesis of the neuraminidase inhibitor 4-deoxy-4-guanidino-neuraminic acid derivative 28 from neuraminic acid has been effected and a number of N-substituted guanidines were also prepared,while further chain-shortened analogues of 28 have been prepared without C-9 then C-8 and then C-7. Other analogues 29 have been prepared from Kdn and the 5-deoxy-derivative 30 has been synthesized from 2-deoxy-D-arafewio-hexose by way of an aldolase-catalysed reaction with pyruvic acid. Neuraminic acid has also been converted into the 3,4-dideoxy-4-guanidino derivative 31.  

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Oxidation of hydioxyl groups to carbonyl groups can form molecules with two aldehyde groups (dialdoses), two ketone groups (diuloses), or an aldehyde and a ketone group (osuloses). Keto acids are known as ulosonic acids. 

Neuraminic acid for 5-amino-3,5-dideoxy-D-g/ycero-D-ga/acfo-non-2-ulosonic acid... 

Names of individual ketoaldonic acids are formed by replacing the ending -ulose of the corresponding ketose by -ulosonic acid , preceded by the locant of the ketonic carbonyl group. The anion takes the ending -ulosonate . The numbering starts at the carboxy group. 

D-etyfhro-Pent-2-ulosonic acid D-arab/no-Hex-5-ulosonic acid... 

Mycarose Mycinose Neuraminic acid (Neu) 2,6-D ideoxy-3- C-methy I-l- ribo- hexose 6-Deoxy-2,3-di-Omethyl-D-allose 5-Amino-3,5-dideoxy-D-g/ycero-D-ga/acfo-non-2-ulosonic acid... 

Class Amino sugar" (usually as acetamido (W-acetyl) derivative Uronic acid Uronate Ulosonic acid Ulosonate The sialic acid family ... 

Synthesis of anomeric phosphates of aldoses and 2-ulosonic acids 71... 

Aldulosonic acids are involved in many important areas of glycobiology and glycomedicine, such as /V-acetylneuraminic acid (Neu5Ac), 3-deoxy-D-glycero-v-galacto-non-2- Aosonic acid (Kdn) and 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo). 

In related work, Rutjes and co-workers reported a four-step protocol from conveniently protected sugar derivatives to substituted C-l glycals (Scheme 16).77 The key step in their synthetic route included RCM of highly functionalized a-alkoxyacrylates. The potential of these glycal derivatives was illustrated by their conversion to natural products such as DAH (3-deoxy-D-arabino-2-heptulosonic acid) or KDO (3-deoxy-D-manno-2-ulosonic acid). 

The TBA assay for 3-deoxyglyc-2-ulosonic acids, used by Weissbach and Hurwitz11 to determine 3-deoxy-D-arabino-2-heptulosonic acid, was subsequently applied by Warren13 and by Aminoff14 to the analysis ofN-acetylneuraminic acid (NeuAc, 5 see Fig. 4). The formation of the 3-formylpyruvate-derived chromophore 4 in the periodate... 

Similar addition of other lithiated thio derivatives to substituted aldonolac-tones has been performed (69). Thus, reaction of tris(methylthio)methyl-lithium to benzylidenated or isopropylidenated aldonolactones, followed by mercury(II)-catalyzed desulfuration, led to derivatives of glyc-2-ulosonic acids. 

SchemB 2 The most important 3-deoxy-2-keto-ulosonic acids.

V. Delest and C. Aug6, The use of Aspergillus terreus extracts in the preparative synthesis of 2-keto-3-deoxy-ulosonic acids, Tetrahedron Asymm. 6 863 (1995). 

A. Dondoni and P. Merino, Chemistry of the enolates of 2-acetylthiazole Aldol reactions with chiral aldehydes to give 3-deoxy aldos-2-uloses and 3-deoxy-2-ulosonic acids. A short total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO), J. Org. Chem. 56 5294 (1991). 

N. Fraysse, B. Lindner, Z. Kaczynski, L. Sharypova, O. Holst, K. Niehaus, and V. Poinsot, Sinorhizobium meliloti strain 1021 produces a low-molecular mass capsular polysaccharide that is a homopolymer of 3-deoxy-D-manno-oct-2-ulosonic acid harbouring a phospholipidic anchor, Glycobiology, 15 (2005) 101-108. 

There are also reports of their occurrence in polysaccharides. 3-Deoxy-D-t/zreo-hex-2-ulosonic acid (120) is a component in the extracellular polysaccharide of Azotobacter vinelandii304 and 3-deoxy-L-g7ycero-pent-2-ulosonic acid (121) has been found as a component of the capsular polysaccharide of Klebsiella type 38.305... 

Deoxy-D-araZhrao-hept-2-ulosonic acid-7-phosphate ( DAHP, 122) is the precursor for the synthesis of aromatic amino acids in all microorganisms and plants (shikimic pathway).306,307... 

As a component of a natural glycoconjugate, the best-known example is 3-deoxy-D-m<2 o-oct-2-ulosonic acid (123), commonly known as Kdo. Compound 123 is part of the core linking the polysaccharide to lipid A in the LPS that is characteristic of Gram-negative bacteria.308 Kdo is usually found in the a-pyranosic configuration, but it may exist as furanoside as in the LPS of Bordetella pertussis.309... 

Selective oxidation at C-2 of 3-deoxyaldonic acids by the action of sodium perchlorate in the presence of vanadium pentaoxide has been used for the preparation of deoxyketoaldonic acids, although low yields of pure compounds are obtained. The necessary 3-deoxyaldonic acids may be prepared by a cyanohydrin chain-extension reaction. Several syntheses have been reported for 3-deoxy-D-araZu rao-hept-2-ulosonic acid starting from 2-deoxy-D-arabino hexose 310,311 DAHP (122) has also been similarly prepared.312... 

Several approaches have been developed for the synthesis of 3-deoxy-D-mararao-oct-2-ulosonic acid (Kdo, 123) the most common one involves the coupling of oxaloacetic acid with D-arabinose followed by decarboxylation. This aldol reaction takes place under basic conditions, but above pH 11 side reactions occur. The procedure is simple and Kdo is isolated as the crystalline ammonium salt.316... 

D-glucono-l,5-lactone (1), 3-deoxy-D-eryt/wo-hex-2-ulosonic acid (119) was synthesized in six steps with 45% overall yield (Scheme 13).317... 

J. Andersch, L. Hennig, and H. Wilde, IV-Glycosidation of D-arabino-hex-2-ulosonic acid,... 

P. A. McNicholas, M. Batley, and J. W. Redmond, Synthesis of methyl pyranosides and furanosides of 3-deoxy-D-marcrco-oct-2-ulosonic acid (KDO) by acid-catalysed solvolysis of the acetylated derivatives, Carbohydr. Res., 146 (1986) 219-231. 

DIAMINO-3,5,7,9-TETRADEOXYNON-2-ULOSONIC ACIDS IN BACTERIAL GLYCOPOLYMERS CHEMISTRY AND BIOCHEMISTRY... 

A new class of ald-2-ulosonic acids, 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids, reported as sialic acids of a new type, was discovered in 1984.9 Members of this class contain an additional amino group at C-7, additional deoxygenation at C-9 (methyl group) and may exhibit configurational differences as compared with neuraminic acid. Unlike sialic acids, the new class of ald-2-ulosonic acids appears to be unique to microorganisms. 

The present article focuses on the occurrence and characterization of derivatives of 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids and presents experimental approaches used to identify them and to elucidate the structures of the bacterial polysaccharides that contain the nonulosonic acids. Recent data on the biosynthesis of these sugars and their role in immune recognition and epitope specificity of bacterial glycopolymers are discussed. 

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