Completely β-Selective Glycosylation Using 3,6-O-(o-Xylylene)-Bridged Axial-Rich Glucosyl Fluoride

Abstract

A completely β-selective glycosylation that does not rely on neighboring group participation is described. The novelty of this work is the design of the glycosyl donor locked into the axial-rich form by the o-xylylene bridge between the 3-O and 6-O of d-glucopyranose. The synthesized 2,4-di-O-benzyl-3,6-O-(o-xylyene)glucopyranosyl fluoride could efficiently react with various alcohols in a SnCl(2)-AgB(C(6)F(5))(4) catalytic system. The mechanism composed of the glycosylation and isomerization cycles was revealed through comparative experiments using acidic and basic molecular sieves. The achieved perfect stereocontrol is attributed to the synergy of the axial-rich conformation and convergent isomerization caused by HB(C(6)F(5))(4) generated in situ.

Conformationally supple glucose monomers enable synthesis of the smallest cyclodextrins

“…On the other hand, the attachment of a bridge between the two discontiguous oxygen atoms on the pyranose ring produces a bicyclic skeleton in which the newly formed ring modulates the conformation of the pyranose scaffold. A short bridge locks the conformation into a motif with more axial substituents, as seen in 5 and 7 (18) and others (19)(20)(21)(22)(23). By contrast, when the O-3 and O-6 atoms were bridged by the EDB group, the pyranose conformation was modified by subtle structural alteration (Fig.…”

Stereodirecting Effect of Cyclic Silyl Protecting Groups in Chemical Glycosylation

“…This reversal of stereoselectivity would attribute to the thermodynamic equilibrium between glycosylated anomers after glycosylation, where the -anomer becomes thermodynamically more stable due to restriction by the 3,6-bridge. Furthermore, the first investigations into glycosyl fluoride donors having a 3,6-tethered (3,6-O-oxylylene) as the -directing factor and the post-glycosylation anomerization under the SnCl 2 /AgB(C 6 F 5 ) 4 promoter system have been reported by Okada et al, (2012). …”

β-Selective Glycosylation Using Axial-Rich and 2-<i>O</i>-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar

“…We have previously reported β-selective glycosylation using ethyl 6-O-pivaloyl-1-thio-2,3,4-tri-O-triisopropylsilyl (TIPS)-β-D-glucopyranoside (1) via the conformational lock strategy [35][36][37][38][39][40][41][42][43][44] based on the steric bulk of silyl-protecting groups 45) (Fig. 1b).…”