Silver carbonate, glycoside synthesis

This method of silver-assisted glycoside synthesis is a variation of the Koenigs-Knorr reaction, which uses silver carbonate. William Koenigs and Edward Knorr first reported their method in 1901. 

In relation to carbohydrate chemistry, the Koenigs-Knorr synthesis of glycosides involves the treatment of glycosyl halides with an alcohol or phenol in the presence of a heavy metal salt.267 Karrer268 discovered that reaction of silver salts of hydros acids could also be used and use of these reagents has been extended more recently. Numerous variations and improvements on the original method have now been reported, and silver oxide, silver carbonate or silver trifluoromethanesulfonate have since become the accepted standard reagents.267... 

The application of Konigs and Knorr s method of glycoside synthesis to acetyl-L-rhamnosyl bromide by Fischer, Bergmann and Rabe resulted in the formation of a mixture of one sirupy and two crystalline isomeric methyl rhamnoside acetates. When acetylrhamnosyl bromide was treated in anhydrous methyl alcohol with dry silver carbonate at room temperature, the solid part of the reaction product consisted of crystalline needles and cubes. The needles consisted of methyl 9-L-rhamnoside triacetate with the expected normal behavior toward alkaline deacetylat-ing agents. The cubes, consisting of 7-methyl L-rhamnoside triacetate ... 

Helferich reported that mercuric cyanide is sometimes superior to silver carbonate as base in the synthesis of glycosides and disaccharides. Thus the condensation of tetra-O-benzoylbromoglucose (1 equiv.) with benzyl alcohol (1 equiv.) in nitro-methane in the presence of mercuric cyanide (1 equiv.) gives tetra-O-benzoylbenzyl-/3-D-glucose in 90% yield. Zorbach used this general procedure, except that 1,2-dichloroethane was used as the solvent, in a successful synthesis of the cardiac-active... 

Koenigs-Knorr synthesis. Formation of glycosides from acetylated glycosyl halides and alcohols or phenols in the presence of silver carbonate or silver oxide. The reaction proceeds with inversion of configuration. 

In the alternative synthesis, the condensation of 85 with 86 was performed in chloroform-l,4-dioxane in the presence of silver carbonate, silver perchlorate, and Drierite. Deacetonation followed by chromatography afforded the protected 6-glycoside (89) and the 4-isomer (91) in almost die same amounts these afforded the tri-N-acetyl derivatives 90 and 92, respectively. 

For the synthesis of alkyl and aryl a-glycosides of sialic acids often Koenigs-Knorr-like procedures have been applied. A large number of these glycosides have been obtained by silver carbonate-promoted condensation of 5-acylamino-4,7,8,9-... 

Besides the 0-glycosides mentioned so far, also attention has been paid to the synthesis of N- and S-analogues. The p-nitrophenyl N-glycoside of a-N-acetylneuraminic acid has been prepared by silver carbonate-promoted reaction of 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-p-N-acetylneuraminic acid methyl ester with p-nitroaniline and subsequent deprotection (Privalova and Khorlin 1969). Treatment of the same precursor with sodium azide, followed by de-esterification, led to the formation of 2-azido-2-deoxy-a-N-acetylneuraminic acid (Supp et al. 1980). The same authors reported also the preparation of the p-form. The azides can readily be converted into the 2-amino derivatives of N-acetylneuraminic acid. Subsequently, the amino function has been benzoylated. Data on the syntheses of the methyl and p-nitrophenyl S-glycosides of a-N-acetylneuraminic acid have been presented by Privalova and Khorlin (1969), whereas Ponpipom et al. (1980) have described a method for the synthesis of 5-acetamido-2-S-[6-(5-cholesten-3p-yloxy)hexyl]-3,5-dideoxy-2-thio-p-D-g/vccro-D-ga/acto-2-nonulopyranosonic acid. 

Deoxy-2,3-dehydro-N-acetylneuraminic acid has been synthesized by treatment of 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-[5-N-acetylneuraminic acid (Meindl and Tuppy 1965 a) with triethylamine (10 min, 20 °C) or silver carbonate (60-90 min, 80 90°C) in dioxan or acetone, and subsequent alkaline O-deacetylation (Meindl and Tuppy 1969 a). This compound has also been detected frequently as a by-product in the synthesis of a-glycosides (Meindl and Tuppy 1965 a) and of a-linked sialodisaccharides (Van der Vleugel / al. 1982 b, 1982 c). 

Privalova and Khorlin (1969) reported the synthesis of the p-nitrophenyl glycoside of a-N-acetylneuraminic acid. The substrate was obtained by glycosylation of p-nitrophenol with 4,7,8,9-tetra-0-acetyl-2-chloro-2-deoxy-p-N-acetylneuraminic acid methyl ester in chloroform in the presence of silver carbonate and Drierite, followed by 0-deacetylation and saponification. In enzymatic reactions, released p-nitrophenol can be determined spectrofoto-metrically. 

The synthesis of prodrug 13 first involved condensation of penta-0-acetyl-D-galactose (15) with para-cresol (16), in the presence of ZnCl2 [56, 57], to afford stereospecifically the a-glycoside 17 [58]. Benzylic bromination of 17 was achieved by treatment with iV-bromosuccinimide in carbon tetrachloride under photolysis conditions. Solvolysis of the bromobenzyl derivative 18 by treatment with silver nitrate in a mixture of acetone and water afforded alcohol 19 [59], which was subsequently activated through reaction with A -hydroxysuccinimidocarbonate to 20. 

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