A 3,4‐trans‐Fused Cyclic Protecting Group Facilitates α‐Selective Catalytic Synthesis of 2‐Deoxyglycosides

Abstract

A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77–97 %) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH⋅H2O (1 mol %) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.

Determination of the Influence of Side‐Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors

“…[9] While the 6-deoxy donor was found to give α,β-mixtures of products, the 6- O -silyl system was found to give exclusively the α-anomer (Scheme 6). The difference in selectivity was attributed on the basis of computational work to the preferential adoption of the gg conformation by the siloxy group and the corresponding stabilization by 2.6 kcal.mol −1 of the oxocarbenium ion with respect to the gt conformer.…”

“…[4f, 9] In this article we report on the synthesis and use of a series of conformationally locked bicyclic mannosyl donors in which the C6-O6 bond is held in either the gg, gt , or tg conformation, to probe the effect of side chain conformation on glycosylation stereoselectivity. We find that the gg configured system has lower β-selectivity than either the gt or the tg comparators consistent with stabilization of the glycosyl oxocarbenium ion by the gg methoxy group and increased S N 1-like character for the glycosylation reaction.…”

Synthesis of Lewis X - O -Core-1 threonine: A building block for O -linked Lewis X glycopeptides

“…Deacetylation under Zémplen conditions afforded triol 17 , which was converted in situ to a 4,6-O-benzylidene acetal 14 by PhCH(OMe) 2 and catalytic CSA. 54 Regioselective ring opening of 14 afforded acceptor 15 .…”

“…The NMR spectra for 11 matched those previously reported. 54 1 H NMR (400 MHz; CDCl 3 ) δ : 6.23 (1H, d, J 3.4 Hz), 5.28 (1H, dd, J 10.7, 9.6 Hz), 5.20 (1H, t, J 9.8 Hz), 5.14 (1H, d, J 9.3 Hz, NHTroc), 4.82 (1H, d, J 12.1 Hz), 4.62 (1H, d, J 12.1 Hz), 4.28 (1H, dd, J 12.4, 4.0 Hz), 4.20 (1H, ddd, J 10.7, 9.4, 3.8 Hz), 4.06 (1H, dd, J 12.5, 2.4 Hz), 4.06–4.01 (1H, m), 2.20 (3H, s), 2.09 (3H, s), 2.04 (6H, 2xs).…”

Organocatalyzed Glycosylation Reactions of Carbohydrates

“…In contrast to thiourea-catalyzed glycosylation the α-configured disaccharide 17 is detected with high degrees of stereoselectivity (Scheme 4.7) [69].…”