Stereodirecting Effects of 4‐O‐ortho‐cyanobenzyl Ether on Chemical Glycosylation with Glucopyranosyl Donor

Abstract

Comprehensive Summary Here we report a systematic investigation on the stereodirecting effects of a 4‐O‐ortho‐cyanobenzyl ether (oBCN) group with a glucopyranosyl donor. Experimental studies revealed that the glycosylation reactions using this donor generally show dual‐stereoselectivities depending on the acceptor nucleophilicity, that is, glycosylation of weak nucleophile acceptors generally affords α‐glycosides specifically while glycosylation of strong nucleophile acceptors affords β‐glycosides preferentially. DFT computations suggested that strong nucleophiles preferentially attack the predominant covalent α‐glycosyl triflate intermediate in an SN2‐like manner, while weak nucleophiles preferentially attack the less stable and more reactive β‐glycosyl triflate with H‐bond mediated direction. The first and facile synthesis of a hexasaccharide repeating unit of serotype IV group B Streptococcus capsular polysaccharide demonstrated the versatile utility of glucosyl building blocks with an oBCN functionality in carbohydrate chemistry.

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

“…Considering the difficulty of α-glycosylation of d -glucose, these interesting results might provide new solutions to the challenging 1,2- cis -glycosylation reactions. 42–45 Additionally, the excellent yields of the glycosylation with lactose-derived CCPB thioglycoside displayed the practicability of our method in the assembly of complex oligosaccharides. An important feature of the current glycosylation reactions was that there was no insertion of the acceptor into DAC sites, indicating that the intramolecular ring-opening of DAC by the anomeric sulfide was favorable over the intermolecular reaction with acceptors of O -, S - and N -nucleophiles.…”

Combination of 3-O-Levulinoyl and 6-O-Trifluorobenzoyl Groups Ensures α-Selectivity in Glucosylations: Synthesis of the Oligosaccharides Related to Aspergillus fumigatus α-(1 → 3)-d-Glucan

“…Glycosylation of 2,2,2-trifluoroethanol (41 μL, 0.571 mmol) with the donor 4 (101.6 mg, 0.142 mmol, α:β = 1:1.8), followed by purification on SiO 2 (40–63 μm) using a petroleum ether–EtOAc, 0 → 10% eluent system, resulted in an anomeric mixture of 20α/β (76.7 mg, 86%) as a foam . The anomeric ratio was defined by the integration of signals in 1 H-NMR of the purified anomeric mixture with BnOBz added as standard.…”

“…17α: colorless glass, R f 0.20 (petroleum ether−EtOAc, 5:1 1.8), followed by purification on SiO 2 (40−63 μm) using a petroleum ether−EtOAc, 0 → 10% eluent system, resulted in an anomeric mixture of 20α/β (76.7 mg, 86%) as a foam. 70 The anomeric ratio was defined by the integration of signals in 1 ), 3.77 (ddd, J 5,4 = 10.0, J 5,6B = 3.8, J 5,6A = 2.0 Hz, 0.64H, H-5 α ), 3.75− 3.71 (m, 1H, H-6A α, β ), 3.71−3.58 (m, 3H, H-6B β , H-4 α , H-3 β , H-4 β , H-6B α , H-2 α ), 3.51 (dd, J 2,3 = 8.9, J 2,1 = 7.7 Hz, 0.36H, H-2 β ), 3.46 (ddd, J 5,4 = 9.3, J 5,6B = 4.6, J 5,6A = 2.0 Hz, 0.36H H-5 β ). 13 C{ 1 H} NMR (151 MHz, CDCl 3 ) δ 138.7 (ipso-Bn), 138.1 (ipso-Bn), 137.7 (ipso-Bn), 128.5, 128.4, 128.1, 128.0, 127.9, 127.9, 127.8, 127.…”