Aldonic acids amides

From a series of sulfated bis-aldonic acid amides with different alkyl spacer length, compound 34 was chosen for further evaluation as an antithrombotic. This compound was synthetically available in four steps from lactobionic acid (Scheme 7). Compound 34 had relatively high APTT values (42 U/mg) and antithrombotic activity, both of which decreased gradually when the number of methylene groups in the spacer was increased. It was thought to act via HCII and multiple sites in the intrinsic pathway of the coagulation cascade [64]. 

N-(Dimethylthio)methylene aldonic acid amides (709) reacted with thio-semicarbazide or phenylhydrazine to give the 3-(alditol-l-yl)-5-methylthio-1,2,4-triazoles 710 [86PHA551 87GEP(D)245875] (Scheme 190). 

Chromatographic analysis of a solution of an aldonic acid revecds the presence of both acid and lactone if present, the latter being represented by the faster moving spot. Aldonic acids, amides, lactones and esters can be detected on a paper chromatogram in the form of their hydroxamic acid derivatives . 

Aldonamides are readily prepared by reaction of lactones with liquid ammonia (86,99,100), with ammonium hydroxide (101,102), or by bubbling ammonia gas into alcoholic solutions of the sugar lactones (103-104). Aldonamides of the tetronic adds are stable in aqueous solution (105), but penton- or hexon-amides are hydrolyzed, as shown by the change of the optical rotation of the amide solutions (106). The hydrolysis is catalyzed by acids and bases, and the product was the ammonium salt of the aldonic acid. 

Similarly, open chain C-nucleosides of adenine have been prepared by condensing 4,5,6-triaminopyrimidine with aldonic acids (or aldonolac-tones) of various chain-lengths. The amides (102) first formed were thermally cyclized, affording the 8-(hydroxyalkyl)adenines (103) in rather low yields (119). 

The question then arises if a regioselective opening of a 2,3-rraMS-epoxy carboxamide derived from aldonic acids would occur. The 2,5-di-O-tosyl-D-ribono-1,4-lactone (62) (Scheme 13) was used to find an answer to this question. If treated with ammonia, the 2,5-diamino-2,5-dideoxy-D-ribono-1,5-lactam (63) was obtained as the only product [79]. The NMR spectra of the reaction mixture showed the formation of the diepoxy amide A which was opened at C-5 by ammonia. In this case no internal lactamization could occur, due to the trans 2,3-epoxy group in B (Scheme 13). Thus, a regioselective opening of an acyclic 2,3-epoxy carboxamide took place at C-2. The reaction was complete within 6 days. 

Pfannemtiller et al. showed that it is possible to obtain carbohydrate-containing amphiphiles with various alkyl chains via amide bond formation. For this, mal-tooligosaccharides were oxidized to the corresponding aldonic acid lactones, which could subsequently be coupled to alkylamines [128-136]. Such sugar-based surfactants are important industrial products with applications in cosmetics, medical applications etc. [137-139]. The authors were also able to extend the attached mal-tooligosaccharides by enzymatic polymerization using potato phosphorylase, which resulted in products with very interesting solution properties [140, 141]. 

The first surface-initiated enzymatic polymerization reported was the synthesis of amylose brushes on planar and spherical surfaces [145]. For this, silica or silicone surfaces were modified with self-assembled monolayers of (3 amino-propyl)trimethoxysilane or chlorodimethylsilane, respectively. To these functionalities, oligosaccharides were added via (a) reductive amidation of the oligosaccharides to surface-bound amines, (b) conversion of the oiigosaccharide to the according aldonic acid lactone and reaction with surface bound amines, and (c) incorporation... 

For a long time, this reaction was conducted exclusively with acety-lated nitriles of aldonic acids, and the products obtained were known in general as "aldose-amides. Fischer2 used this reaction to transform tetra-O-acetyl-L-rhamnononitrile into l,l-bis(acetamido)-l,5-dideoxy-L-arabinitol, whose subsequent hydrolysis and oxidation allowed him to determine the configuration of dextro-tartaric acid (L-threaric acid). 

Brigl and coworkers9 discovered the first example showing that the formation of aldose amides is not restricted to the degradation of acylated nitriles of aldonic acids. By ammonolysis of 2,3,4,5,6-penta-O-benzoyl-aldehydo-n-glucose (16), they obtained l,l-bis(benz-amido)-l-deoxy-D-glucitol (17). 

Aldonic acids form crystalline esters, amides, hydrazides, and benzimidazoles. Many of these derivatives, as well as the lactones, have been valuable... 

Esters are prepared by reaction of aldonic acids or lactones with an alcohol in the presence of hydrogen chloride 80 the reaction is slower with 1,4-lactones. Amides are readily formed from lactones by reaction with liquid ammonia followed by evaporation of the solvent.81 D-Gluconamide has also been prepared by treatment of D-glucono-1,5-lactone with concentrated ammonium hydroxide and subsequent precipitation with ethanol.82 A-Substituted aldonamides may be obtained by reaction of the aldono-lactones with ethanolamine, diethanolamine, and related species.83... 

Fully acetylated aldonic acids can be prepared by oxidation of aldehydo-sugar peracetates. Direct acetylation of certain aldonic acid salts is possible, and addition of cadmium salts, in particular, affords high yields of acetates. The synthesis can also be accomplished by deamination of the readily prepared, acetylated amides with nitrous acid or nitrosyl chloride. Examples of the various methods are given in Ref. 86. 

The oxidation of some hexoses49 and pentoses50 by A-chloroarylsulfon-amides in alkaline conditions has been conducted, and the kinetics studied. The products were identified as the corresponding aldonic acids for aldoses, and arabinonic acid for fructose. Further studies51 indicated that both... 

Deamination iff amides. Wolffom " found that penla-O-acetylmannonamide can be deaminatsd smoothly to the corresponding aldonic acid pentaacetate by... 

Weerman degradation. Formation of an aldose with one less carbon atom from an aldonic acid by a Hoffmann-type rearrangement of the corresponding amide. This is a general reaction of a-hydroxy carboxylic acids. 

The cyanohydrin synthesis is particularly important in the carbohydrate series Fischer thus converted, e.g., pentoses into hexoses by way of the lactones of the aldonic acids which he later reduced. Admittedly, the nitriles produced as intermediates (best obtained in other cases by dehydration of the corresponding oximes) are generally not isolated. On the other hand, the corresponding amides can often be separated in a pure state, as shown, e.g., by Kiliani166 for heptonamide ... 

Aldonic Acids, Aldaric Acids, and Their Amides, Lactones and Lactams... 

The aldonic acids are the initial oxidation products produced from aldoses by most oxidants and are usually isolated as the metallic salts or the lactones. As a result of the ease with which the crystalline lactones, salts, amides, hydrazides, and other derivatives can be formed, aldonic acids are... 

The amides of the aldonic acids can be formed readily by the action of liquid ammonia on the lactones (29). These derivatives are often crystalline... 

Many derivatives of aldonic acids and amino acids have been made by the condensation of 0-acetylaldonyl chlorides with amino acids or their esters. Deactylation gave the esters or amides and, in a few instances, the free iV-aldonylamino acids 194)-... 

A study has been made by electron microscopy of the aggregation behaviour of a series of N-octylaldonamides. and a number of bis(2-chloroethyl)amides of aldonic acids have been prepared from the per-Q-acetyl... 

Aldonic acids usually yield crystalline lactones, amides and other derivatives and have proved of value in the characterisation of sugars. No appreciable amounts of aldonic acids have been found in plants or animals, although certain bacteria are capable of oxidising glucose and other aldoses to the corresponding aldonic acids. Lactones have proved to be powerful inhibitors in certain enzymic reactions involving substances having structures related to the inhibitors . 

Other functional groups are also found in natural sugars such as carboxylic acids (aldonic, uronic, aldaric) able to form lactones (reversibly), amines or amides (aminosugars) and both acid and amine groups (sialic acids). 

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