N‐Benzyl‐2,3‐trans‐Carbamate‐Bearing Glycosyl Donors for 1,2‐cis‐Selective Glycosylation Reactions

Abstract

Glycosyl donors for the preparation of 1,2‐cis glycosides of amino sugars have been developed. The 2,3‐trans‐cyclic‐carbamate‐carrying glycosyl donors were readily prepared from the corresponding known trichloroethyl carbamate protected amino sugars under standard hydroxy group benzylation conditions. The donors exhibit high 1,2‐cis stereoselectivity towards secondary hydroxy group substrates. In the case of primary hydroxy acceptors, high stereoselectivities were achieved with the aid of the dioxane effect. After glycosylation, the carbamate was removed under alkaline conditions. Importantly, these glycosyl donors can be used in polymer‐supported and solid‐phase synthesis.

Influence of protecting groups on the anomeric equilibrium; case of the 4,6-O-benzylidene acetal in the mannopyranose series

“…38 Concerning the influence of cyclic protecting groups on the anomeric equilibrium, we noted that a 2N,3O-oxazolidinone in the glucosamine series both facilitates the interconversion of β- to α-anomers and strongly favors the α-anomer. 23 Similar observations were made by the Oscarson, Ye, and Ito groups, 25,26,40,28,29,41–43 all of which concluded that the equilibration occurs via an endocyclic cleavage mechanism.…”

Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

“…125,129 Ito and coworkers showed the N -benzyloxazolidinone protected glucosamine donor 78 (Fig 8) to be unselective at low temperatures and α-selective at room temperature and, like Oscarson, came to the conclusion that this was the result of an equilibration process involving endocyclic cleavage. 130 …”

Probing the Influence of a 4,6-O-Acetal on the Reactivity of Galactopyranosyl Donors: Verification of the Disarming Influence of thetrans–gaucheConformation of C5–C6 Bonds

“…1–9 In particular, in recent years, cyclic protecting groups 10 have proven to be especially useful in controlling the stereochemistry of what were previously considered to be difficult glycosylations. Prominent examples include the 4- O ,5- N -oxazolidinones in the sialic acid series, 11–15 the 3,5- O -(di- tert butyl) silylene acetals and related groups in the arabinofuranoside series, 16–18 the 2 N ,3 O -oxazolidinones in the 2-amino-2-deoxyglucopyranose series, 19–21 and the 4,6- O -benzylidene acetals in both the gluco- 22–23 and mannopyranoside series. 24–25 In most cases mechanistic understanding lags someway behind application of these mostly serendipitous discoveries owing to the complex nature of glycosylation reactions, but significant progress has been made on the origins of the 4,6- O -benzylidene effect in gluco- and mannopyranosylation.…”