Koenigs-Knorr reaction, synthesis glycosides

Koenigs-Knorr reaction (Section 25.6) A method for the synthesis of glycosides by reaction of an alcohol with a pyranosyl bromide. 

A number of glycosides were available to Fischer by way of the Koenigs-Knorr reaction and his own glycoside synthesis, which involves treatment of... 

Despite its wide application in glycoside synthesis, the Koenigs-Knorr reaction suffers from several disadvantages (i) the glycosyl halides are unstable, (ii) excess toxic heavy metals are needed to activate the donor, and (iii) a desiccant (to absorb any liberated water) and an acid acceptor (to absorb the liberated hydrogen halide and can be a promoter itself) are often needed to increase the yield and suppress side reactions. 

Wulff, G., Roehle, G. Glycoside synthesis. VI. Kinetic investigations on the mechanism of Koenigs-Knorr reaction. Chem. Ber. 1972,105, 1122-1132. 

Although these methods often give excellent results, and some of them are applicable to the synthesis of complex glycosides, this article deals mainly with the Koenigs-Knorr reaction. 

In 1901, Koenigs and Knorr published an efficient method for the preparation of alkyl and aryl O-glycosides [89]. The Koenigs-Knorr reaction has for a long time been the best method achievable for the synthesis of O-glycosides. This method has been widely studied and improved in the years [31,90,91], and although valuable alternatives are now established, it still is the method of choice when more sophisticated procedures fail. 

The synthesis of N-(2,4-dinitrophenyl)-3-0-(tetra-0-acetyl-yJ-D-glu-copyranosyl)-L-threonine methyl ester (131) involved a two-step procedure. First, formation of the intermediate, L-threonine orthoester 130 was achieved by treatment of tetra-O-acetyl-a-o-glucopyranosyl bromide (128) with the methyl ester of N-(2,4-dinitrophenyl)-L-threonine (129) under the conditions of the Koenigs-Knorr reaction (see next paragraph), and this was then converted into the L-threonine glycoside 131. 

A book (Jmo pp.) has been published by Russian authors entitled Chemistry of the 0-Glycosidic Bond / and a symposium sponsored by the American Chemical Society on the anomeric effect yielded several relevant reports, including one on the influence of reactant structure and solvent on glycosidation reactions/ A further review has appeared on the Koenigs-Knorr reaction applied to the synthesis of both pyranosides and non-pyranoid glycosides, and a more specific one on glycosidation processes applied to drugs/... 

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. 

The other two general reactions for the synthesis of glycosides require the fully acetylated sugar as starting-materiaL In the Koenigs-Knorr reaction, this is next converted into the acetylglyco l halide, whilst in the Helferich reaction it is used directly. 

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