Solvent free, catalytic and diastereoselective preparation of aryl and alkyl thioglycosides as key components for oligosaccharide synthesis

Abstract

A new and environmentally friendly protocol for conversion of sugar per-acetates into thioglycosides under solvent free and catalytic conditions is presented. The procedure involves heating in the presence of InCl3...

Formation of β-Configured Thioglycosides ofd-Glucosamine andd-Galactosamine and Synthesis of Protected Human Milk Oligosaccharides

“…We found that the β-1,3,4,6-tetra-O-pivalate 2 could also be formed under more forcing conditions with slow addition of PivCl (Scheme 2). Tetrapivalate 2 was found to react smoothly with thiophenol (PhSH) and cyclohexylthiol ( c HexSH) under solvent-free conditions, 26 but both temperature (from 100 to 135 °C) and catalyst loading (from 1−2 mol % to 5 mol %) of InCl 3 were increased compared to the analogous reaction for β-glycose pentaacetates (Scheme 3). This is in accordance with our expectations from earlier projects, where pivalate esters need more forcing conditions for activation compared to analogous acetate esters.…”

“…We opted to use the cyclohexyl-functionalized glycosyl donor 9 since we have previously found that more reactive (alkyl) thioglycosyl donors return a higher level of β-selectivity than their less reactive (phenyl) counterpart. 26,27 For the synthesis of LNT, the 4-and 6-positions were first blocked by benzylidene formation, upon which Schmidt 40 galactosylation could occur on the open 3-OH with galactosyl trichloroacetimidate 13. Next, the glycosylation was attempted on a lactose-based acceptor 15, but this failed to give the desired product.…”

“… Both of these have been chemically synthesized before using a variety of elegant procedures, − but rarely with a 2-azido-substituted building block. We opted to use the cyclohexyl-functionalized glycosyl donor 9 since we have previously found that more reactive (alkyl) thioglycosyl donors return a higher level of β-selectivity than their less reactive (phenyl) counterpart. , …”

“…We have recently published a fast, catalytic, and solvent-free method for the diastereoselective synthesis of aryl and alkyl thioglycosides from peracetylated saccharide starting materials . We were curious to investigate whether this procedure could also be employed to generate thioglycosides of GlcNAc as a single β-anomer and later convert the 2-NHAc functionality to substituents such as 2-azido that are more compatible with oligosaccharide synthesis (Scheme ).…”

“…We have recently published a fast, catalytic, and solvent-free method for the diastereoselective synthesis of aryl and alkyl thioglycosides from peracetylated saccharide starting materials. 26 We were curious to investigate whether this procedure could also be employed to generate thioglycosides of GlcNAc as a single β-anomer and later convert the 2-NHAc functionality to substituents such as 2-azido that are more compatible with oligosaccharide synthesis (Scheme 1). Although a good protocol for the synthesis of 2-azido α-thioglycosides exists, 22 it could be beneficial to also have a good synthesis of its anomer, as we have recently demonstrated that glycosyl donor stereochemistry can have a vast impact of glycosylation selectivity.…”