Fischer glycosylation

Scheme 2. Fischer glycosylation of GalNAc catalyzed by acid zeolites.

Fischer Glycosylation of GalNAc with Methanol Followed by Acetylation (Compounds 8 and 11),... 

Classically, Bronsted acids are the promoters of the Fischer glycosylation. Though substrate complexity is still limited in scope, recent developments in these reagents more commonly allows for disaccharide synthesis (Scheme 3.3). For instance, Koto et al. have reported that the combination of methanesulfonic acid (30 mol%) and... 

One of the first attempts to synthesize cardiac glycosides was made by Zorbach et al. in 1963 [102] by Fischer glycosylation. After treatment of digitoxigenin and unprotected digitoxose in dioxane with a saturated solution of hydrogen chloride in dichloromethane, 5.4% of the a- and 4.5% of the desired (5-glycoside were isolated after chromatographic purification. 

Catalysis with protic acids has traditionally been used in Fischer glycosylations. As with the recent variations of the above procedure, Lewis acid catalysis is also valuable for dehydrative glycosylations with protected derivatives (Scheme 4.40). Trimethylsilyl triflate has been shown to promote reactions of glucuronic acid hemiacetals [420], and pyridine and TMSOTf was used for the synthesis of cw-glucosides [421]. Pyridinium / -toluenesulfonate (PPTS) was used for the synthesis of glycosides of the biologically important Kdo [422]. 

Scheme 3 Fischer glycosylation [3]. R = methyl, ethyl, n-propyl, i-propyl, amyl, allyl, benzyl, etc.

Acid catalysis in glycosylations with 1-hydroxy glycosyl donors has traditionally employed the Fischer glycosylation procedme or variants thereof in which simple glycosyl acceptors are employed in vast excess. Within the last several years, a series... 

Miiller and Wilhelms applied the Fischer glycosyl thiocyanate method to the preparation of 6-deoxy-6-thiocyano-D-glucose and further explored the synthesis of l-D-glucosyl-2-thiourea. These workers have examined the question of the isomerization of thiocyanates and isothiocyanates, and have made some observations which should prove exceedingly useful. 

The Fischer glycosylation involves the use of acids mineral acids such as HCl, HF, and H2SO4 have been applied successfully [15-23]. p-Toluenesulfonic acid can also be used. The use of homogeneous acids results in the need for neutralization and washing steps, and the inconvenience of possible corrosions in the unit... 

By means of an ETHOS MR oven, Nuchter et al. [33] accomplished scaling-up of a microwave-assisted Fischer glycosylation to the kilogram scale with improved economic efficiency. In batch reactions, carbohydrates (o-glucose, o-mannose, d-galactose, butyl o-galactose, starch) were converted on the 50-g scale (95-100% yield, from 95 5 to 100%) with 3-30-fold molar excesses of an alcohol (methanol, ethanol, butanol, octanol) in the presence of a catalytic amount of acetyl chloride under pressure (microwave flow reactor, 120-140 °C, 12-16 bar, 5-12 min) or without applying pressure (120-140 °C or reflux temperature, 20-60 min). Furano-sides are not stable under these reaction conditions. 

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