Aldonic acids, acetylated

This method for the synthesis of higher-carbon ketoses is based on the reaction of diazomethane with an acid chloride to give a diazomethyl ketone which, on hydrolysis (or acetolysis), furnishes a hydroxy (or acetoxy) methyl ketone. The reaction was first applied in the sugar field in 1938 and has since been widely used in the synthesis of ketoses by Wolfrom and coworkers. As developed by Wolfrom, the synthesis uses fully acety-lated derivatives in the following stages aldose — acetylated aldonic acid acetylated aldonyl chloride acetylated diazomethyl ketose — acetylated ketose — ketose. The method is illustrated in the synthesis of D-galacto-heptulose (10). ... 

Aldose —> acetylated aldonic acid — acetylated aldonyl chloride —>... 

Aldono-1,5-lactones and free aldonic acids react with alcohols in the presence of hydrogen chloride to give the corresponding alkyl aldonates (84). The reaction is slower with 1,4-lactones. Because esterification takes place very slowly in the absence of an acidic catalyst, aldonic acids and their lactones may be recrystallized from boiling alcohols without appreciable esterification (85). However, in some instances, alkyl esters are formed under these conditions. For example, essentially pure ethyl L-mannonate was isolated (6.4% yield) from the mother liquors of crystallization L-man-nono-1,4-lactone, obtained by Kiliani synthesis from L-arabinose (86). Similarly, repeated recrystallization from ethanol of crude 2,3,4,6-tetra-O-acetyl-D-glucono- 1,5-lactone afforded the corresponding ethyl gluconate derivative (87). 

Acetylated nitriles of the aldonic acids are crystalline solids that are very soluble in most nonpolar organic solvents (chloroform, ether, benzene), less soluble in the alcohols usually employed for recrystallization, and almost insoluble in cold water some compounds have a remarkably high solubility in water at elevated temperatures. 

The nitrile group is very sensitive to alkalis and the elimination of it by the action of potassium hydroxide on acetaldehyde cyanohydrin was described by Simpson and Gauthier as one of the reactions of the acetaldehyde cyanohydrin, a substance that they prepared for the first time. That the nitriles of the aldonic acids yield cyanides under the action of alkali, is described by Wohl as one of the properties of penta-acetyl-D-glucononitrile. 

Removal of the acetyl and nitrile groups by acid hydrolysis was also achieved by Wohl, who isolated a pentosazone from the products from heating pentaacetyl-D-glucononitrile with 2 N hydrochloric acid. Fischer also isolated what is now known to have been a 5-desoxy-L-arabinosazone from the products obtained by treatment of tetraacetyl-L-rhamnononitrile with 5% hydrochloric acid. At the same time partial transformation of the nitrile into the aldonic acid takes place as shown by Maquenne, who obtained D-xylonic acid by treating tetraacetyl-D-xylononitrile with concentrated hydrochloric acid. 

With the exception of V-acetyl-D-glucofuranosylamine studied by Hockett and Chandler, all the acetylated nitriles of the aldonic acids (60) G. Zempl4n, Ber., 69, 2402 (1926). 

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). 

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. 

Fully acetylated aldonyl chlorides have been prepared by treatment of acetylated aldonic acids with phosphorus pentachloride87 or thionyl chloride.88 Dichloromethyl methyl ether was later shown to afford the derivative of D-gluconic acid in almost quantitative yield.89... 

M. L. Wolfrom and A. Thompson, Fully acetylated aldonic acids, Methods Carbohydr. Chem., 2 (1963) 21-23. 

The regioselective functionalisation of aldonolactones is possible at the position a to the lactone and at the primary (co) position. The most efficient method for this functionalisation is treatment of the aldonolactone/aldonic acid with hydrogen bromide in acetic acid (Scheme 1). In this strongly acidic medium the lactone is partly acetylated followed by formation of acetoxonium ions. These then undergo opening with bromide ions to give acetylated bromodeoxyaldonolactones (7). The formation of acetoxonium ions controls the... 

The first question concerns the nature and relative proportions of constituent monosaccharides. In principle, this is obtained by acidic hydrolysis (Biermann 1988) but, in practice, it must be carefully applied as there are a certain number of important specific cases. Hydrochloric, sulfuric, and trifluoroacetic acids are used whose 1 N solutions have a pH of 0.1, 0.3, and 0.7, respectively. When hydrolysis liberates monosaccharides fragile in an acidic medium, a delicate balance between the risk of incomplete hydrolysis and partial destruction of the hydrolysis product must be maintained. The fragile sugars are pentoses, deoxy sugars, and uronic and aldonic acids. When sialic acid is kept for 30 min at 90°C in 0.01 M HCl, 20% decomposition occurs. With neutral polysaccharides, decomposition can be limited to less than 9%. The acetyl groups of acetamides are hydrolysed and relatively stable protonated amino sugars are obtained. 

Compounds 312 were also prepared by alternative routes that comprised cyclocondensation of aldonolactones (313) with 1-hydrazinophthalazines or aldonic acid hydrazides (315) with 1-chlorophthalazines. Their acetates 316 were obtained by direct acetylation of 312 or by condensation of aldonoyl chloride acetates (38) with 1-hydrazinophthalazines (90MI6) (Scheme 96). l,2,4-Triazolo[3,4-a]phthalazin-3-yl acyclo C-nucleosides derived from reducing disaccharides were similarly prepared (90MI2). 

Acetylated 1-bromo- and 1-chloro-l-deoxyketoses are readily prepared from the acetylated aldonic acid containing one fewer carbon atoms by the sequence... 

Acetylated aldonic acids can be prepared (a) by direct acetylation of the cadmium salts of aldonic acids in the presence of hydrogen chloride, ... 

Sowden s initial work with Hurd concerned the preparation of tritylated glycerols, and this became the subject of their first publication. Typical of the work in Hurd s laboratory was the problem on acetylated aldonic acids which was featured in Sowden s doctoral dissertation. This study was begun in October, 1935, and characteristically excellent laboratory results developed very rapidly. Hurd and Sowden were interested in the application of F. Arndt s diazomethyl ketone synthesis to ascension of the sugar series, and sought (as it turned out later, with several other investigators) a new route to the acetylated aldonic acids. Sowden presented the sequence ... 

On oxidation (with hypoiodite) to the corresponding aldonic acid, of the disaccharide obtained by partial hydrolysis of chitin, and acetylation with sodium acetate in acetic anhydride, the product undergoes /3-elimination, to give the bionic acid derivative 2-acetamido-4-0-(2-acetamido-tri-0-acetyl-2-deoxy- -D-glucopyranosyl)-6-0-acetyl-2,3-dideoxy-D-erj/(firo-hex-2-enono-1,5-lactone (90). In the original work, the determination of the site... 

Reduction of an aldose forms one alditol reduction of a ketose forms two alditols. Br2 oxidizes aldoses, but not ketoses ToUens reagent oxidizes both. Aldoses are oxidized to aldonic acids or aldaric acids. Aldoses and ketoses react with three equivalents of phenyUiydrazine, forming osazones. C-2 epimers form identical osazones. The Kiliani-Fischer synthesis increases the carbon chain of an aldose by one carbon— it forms C-2 epimers. The Ruff degradation decreases the carbon chain by one carbon. The OH groups of monosaccharides react with acetyl chloride to form esters and with methyl iodide/silver oxide to form ethers. 

O-acetyl-O-methyl-D-glucononitriles methylated sugar derivatives, a review permethylated alditols and aldonic acids... 

The branched-chain aldonic acid derivative (1) has been shown to be a component of avilamycin by isolation of the product (2) of mild methanolysis and acetylation the latter compound was structurally characterized by X-ray analysis. ... 

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