Glycoside acetates, deacetylation

Although Koenigs and Knorr isolated a small yield of methyl /3-n-gluco-pyranoside (as such) from a solution of tetra-O-acetyl-a-D-glucopyranosyl bromide in methanol that had stood at room temperature for several days, it is customary to add an acid acceptor to speed up the reaction and to prevent deacetylation of the product. Silver, in the form of the oxide or a salt, was the first acid acceptor to be employed, and is still the one in most common use. Unless the aglycon is a simple alcohol, it is usual to dissolve the reactants in a solvent, which is often an organic base to act as an additional acid acceptor. Walden inversion at Cl is almost the invariable rule when the reaction is done in the presence of silver ion. Under special circumstances, however, both anomeric glycoside acetates may be obtained. ... 

With the exception of the Fischer reaction, the general methods employed for the formation of the glycoside bond result in the formation of glycoside acetates (or benzoates). Deacylation is accomplished by treatment with alkali, to which the glycoside bond is stable, unless the bond approximates to the ester type. The original method of deacetylation was by quantitative saponification with sodium hydroxide, potassium hydroxide, or barium hydroxide. It was noted, however, that, in anhydrous media, much less than the theoretical amount of alkali was required, and the reaction has since been made entirely catalyt.ic, with considerable gain in efficiency and convenience. The same methods have been employed for debenzoylation. 

The first recorded use of this type of reagent in carbohydrate chemistry was made by Fischer and Bergmann who found that only 0.2 mole of sodium ethoxide was required for complete deacetylation of a sugar or glycoside acetate in ethanol at room temperature. This method was modified by Zempl6n, mainly in connection with a study of cellobiose derivatives. The acetate was dissolved in chloroform, and a solution of sodium methoxide (0.1 to 0.2 molar proportion) in methanol was added. A gelatinous, addition compound separated at 0° and was decomposed by the addition of water. After neutralization, the aqueous layer was processed in the usual way (see Section IV, 1). 

It was subsequently shown that a solution or suspension of a glycoside acetate in absolute methanol can be completely deacetylated in a few minutes on the boiling-water bath by using catalytic quantities of sodimn methoxide (about 0.002 molar proportion), with production of methyl acetate. This method is of very wide application. 

Deacetylation of the glycoside acetates is necessary after the Helferich and Koenigs-Knorr reactions. Aqueous alkali is no longer used for this purpose. The reagent most commonly employed is sodium methoxide in very small, catalytic quantities, and the acetate is dissolved in anhydrous methanol or a mixture of methanol and chloroform. Reaction is usually very rapid. Alternative reagents often used for deacetylation are barium and ammonium methoxides the former is particularly useful for debenzoylation. 

A mixture of triacetyl-a-D-fructofuranoside (1521, a, R2 = OMe) and triacetyl-jS-D-fructopyranoside (1523, R1 = Me) was obtained when the crude glycoside mixture obtained in the glucosidation of 1448 in methanol containing 1% hydrogen chloride at room temperature for 5 hr was ace-tylated with acetic anhydride in the presence of pyridine a 0°C for 3 days (86MI10). The Zemplen deacetylation of 1521 (R2 = OMe) was carried out in quantitative yield. 

We have found that the secret to a successful synthesis of the alkenyl glycosides 64 lies in obtaining the pure -acetate 65 [47]. Condensation of the acetate 65 with the appropriate alkenol,in the presence of a small amount (5-20 mol% depending on the scale) of trimethylsilyl triflate, gave the alkenyl glycosides 64 in excellent yield. Oxidation of the alkene 64 with dimethyldioxirane, followed by deacetylation, then gave the putative enzyme inhibitors 60. 

The complete hydrolysis of the soluble cellulose derivative required gradual addition of water and, preferably, acid. Water can act on cellulose acetate hydrogensulfate in three ways (a) saponification of sulfate groups, (b) saponification of acetate groups, and (c) hydrolysis of glycosidic bonds. Reaction (a) is most rapid and occurs under the mildest conditions. As Table II shows, the product is not any more water soluble (Entries 1-4). Under more severe conditions, the deacetylation (b) has proceeded to water-soluble products, the total amount of dissolved carbohydrates corresponding to theory (Entries 5-10). How-... 

In an alternative route employing fewer overall steps, Borbas and Lipt k119 synthesized the trisaccharide hapten as a 4-aminophenyl glycoside protected as the (V-trifluoroacetyl derivative 13 for potential conjugation to protein.108 Ethyl 1-thio-a-L-rhamnopyranoside as the 2,3-O-diphenylmethylene acetal 23 was the precursor for both rhamnosyl residues. Condensation of 23 with glycosyl bromide 24 with silver triflate as promoter, followed by O-deacetylation and O-benzyliden-... 

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