Influence of the Side Chain Conformation on Glycosylation Selectivity in Furanosides

Glycosylation reactions stereoselectivity depends on various factors and among them, side-chain configuration and conformation have been showing significant roles in influencing the reactivity and selectivity in bicyclic glycosyl donors. Moving to monocyclic donors, this effect has been revealed in glycosylation reactions of sialic acid donor series and simple pyranoside series. We studied the extension of this concept towards furanosides by synthesizing two suitably protected epimers of 5-methyl-D-xylose from D-xylose. Conformational analysis of the 6-deoxy-D-glucofuranoside epimer shows its side chain to take up the trans,gauche-conformation, while that of the 6-deoxy-L-idofuranoside takes up the gauche,trans-conformation. In glycosylation reactions, the 6-deoxy-D-glucofuranose isomer gave predominantly β-glycosides, while the 6-deoxy-L-idofuranose gave α-glycosides as major. These studies reveal that the influence of side-chain conformation on glycosylation reactivity and selectivity is not limited to the sialic acid series but also encompasses simple furanosyl donors.

References

1. Henrik Helligsø Jensen, Lars Ulrik Nordstrøm, and Mikael Bols The Disarming Effect of the 4,6-Acetal Group on Glycoside Reactivity:  Torsional or Electronic? J. Am. Chem. Soc. 2004 126, 9205-9213.

2. Kancharla, P. K.; Crich, D., Influence of side chain conformation and configuration on glycosyl donor reactivity and selectivity as illustrated by sialic acid donors epimeric at the 7-position. J. Am. Chem. Soc. 2013, 135, 18999-9007.

3. Popik, O.; Dhakal, B.; Crich, D., Stereoselective Synthesis of the Equatorial Glycosides of Legionaminic Acid. J. Org. Chem. 2017, 82, 6142-6152.

4. Dhakal, B.; Crich, D., Synthesis and Stereo controlled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups. J. Am. Chem. Soc. 2018, 140, 15008-15015.

5. Ngoje, P.; Crich, D., Stereo controlled Synthesis of the Equatorial Glycosides of 3-Deoxy-d-manno-oct-2- ulosonic Acid: Role of Side Chain Conformation. J. Am. Chem. Soc. 2020, 142, 7760-7764.