Glycoside formation, stereoselectivity

Recent developments in the enzymatic synthesis of carbohydrates can be classified into four approaches 1) asymmetric C-C bond formation catalyzed by aldolases (1-10 2) enzymatic synthesis of carbohydrate synthons (loll) 3) asymmetric glycosidic formation catalyzed by glycosidases (12.-17) and glycosyl transferases (18-23.) and 4) regioselective transformations of sugars and derivatives (24-25). These enzymatic transformations are stereoselective and carried out under mild conditions with minimum protection of functional groups. They hold promise in preparative carbohydrate synthesis. In connection with this book, we focus on the first two approaches. 

SCHEME 6.28 Mong s stereoselective one-pot synthesis using DMF as the novel additive to facilitate the 1,2-as-glycoside formation, (a) The glycosyl imidates formed with DMF. (b) The one-pot synthesis of trisaccharide 142. 

Bp3-Et20 resulted in a shift of stereoselectivity towards 3-glycoside formation in the synthesis of sordaricin [345]. 

As shown, the glycosylation reaction of the succinoyl tethered compounds (157, 159 and 161) was performed by promotion with NIS and TMSOTf in acetonitrile. The (2 -3)-tethered compound (157) afforded the a-glucopyranoside (158) in excellent yield. Similarly, the (2 -3)-tethered (159) and also the (6 -3)-tethered (161) galactose derivatives afforded the cis-glycosides (160 and 162). The stereoselectivity of these reactions is noteworthy as both the acyl-type neighboring group in the donor and the nitrile type solvent favor trawi-glycoside formation. 

Insoluble silver salts such as silver silicate favor direct Sn displacement of an anomeric bromide by alcohols [88]. When applied to 2-deoxy-pyranosyl bromides, this procedure can lead to 2 -deoxy-P-disaccharides with a good stereoselectivity. For instance (Scheme 32), bromide 141, where an ester group at 0-4 can also favor [85] P-glycoside formation, reacted with the sugar alcohol 142 in the presence of silver silicate to give the disaccharide 143 in 85% yield (P a 5.4 1) [89]. 

Preparation of the corresponding a isomers of these C-dimers requires only slight modification of the syntheses, as illustrated in Scheme 39 by simple reversion of the order of the synthetic steps in the preparation of the acyclic precursor. Hence, the isopropylidene in intermediate 141 was hydrolyzed, followed by diol cleavage and preparation of the anomeric />-nitrobenzoate 146. Introduction of the C6 carbon could be achieved by stereoselective allenylation resulting in formation of the manno derivative 147 after chair inversion. Oxidative cleavage then reduction of the allene moiety and subsequent debenzylation and methyl glycoside formation led to the a-D-Man(l-4)-D-Glc carbon analog 148. Access to methyl C-maltoside 149 was... 

FMOC-Cl has been used for 3, 5 -hydroxyl protection of deoxyribose for the introduction of modified bases such as aza-cytidine using the classical Vorbriiggen reaction. While the carbonate protecting groups do not alter the stereoselectivity of the (V-glycoside formation, the FMOC groups can be removed under much milder conditions (EtyN/pyridine) than the typical 4-methylbenzoyl group (eq 9). 

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