187274-83-5

Upstream product

• 767-00-0 4-cyanophenol 
• 604-69-3 β-D-glucose pentaacetate 
• 3947-62-4 2,3,4,5-tetra-O-acetyl-D-glucopyranose 
• 126747-14-6 4-cyanophenylboronic acid 
• 572-09-8 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 
• 6919-96-6 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 

Downstream Products

• 28217-36-9 4-cyanophenyl β-D-glucopyranoside 

Relevant academic research and scientific papers

Copper-mediated O-arylation of lactols with aryl boronic acids

An efficient and novel methodology to access phenolic glycosides has been established by using copper-mediated coupling reaction of aryl boronic acids with hemiacetals. The reaction takes place normally in the presence of Cu(OAc)2 (1.0 equiv.) and pyridine (2.0 equiv.) at 40 °C. This protocol distinguishes itself by wide substrate scope, operational simplicity and giving rise to a myriad of phenolic glycosides in good to excellent yields.

Application of silver N-heterocyclic carbene complexes in O-glycosidation reactions

We report the efficient O-glycosidation of glycosyl bromides with therapeutically relevant acceptors facilitated by silver N-heterocyclic carbene (Ag-NHC) complexes. A set of four Ag-NHC complexes was synthesized and evaluated as promoters for glycosidation reactions. Two new bis-Ag-NHC complexes derived from ionic liquids 1-benzyl-3-methyl-1H-imidazolium chloride and 1-(2-methoxyethyl)-3-methylimidazolium chloride were found to efficiently promote glycosidation, whereas known mono-Ag complexes of 1,3-bis(2,4,6- trimethylphenyl)imidazolium chloride and 1,3-bis(2,6-di-isopropylphenyl) imidazolium chloride failed to facilitate the reaction. The structures of the promoters were established by X-ray crystallography and these complexes were employed in the glycosidation of different glycosyl bromide donors with biologically valuable acceptors, such as estrone, estradiol, and various flavones. The products were obtained in yields considered good to excellent, and all reactions were highly selective for the β isomer regardless of neighboring group effects.

O-Glycosidation reactions promoted by in situ generated silver N-heterocyclic carbenes in ionic liquids

We herein report O-glycosidation reactions promoted via silver N-heterocyclic carbene complexes formed in situ in ionic liquids. Seven different room temperature ionic liquids were screened for the glycosidation reaction of 4-nitrophenol with tetra-O-acetyl-α-d-galactopyranosyl bromide. Good to excellent yields were obtained using Ag-NHC complexes derived from imidazolium halide salts to promote the glycosidation reaction, whereas yields considered moderate to low were obtained without use of the silver carbene complex. Anion metathesis of the ionic liquids with inexpensive alkylammonium halides also resulted in silver N-heterocyclic carbene formation and subsequent O-glycosidation in the presence of silver carbonate. Effective utility of this methodology has been demonstrated with biologically relevant acceptors (including flavones and steroids) where O-β-glycoside products were obtained selectively in moderate to good yields. We have also demonstrated that the Ag-NHC complex is a superior promoter to traditionally used silver carbonate for the glycosidation of polyphenolic acceptors. The ionic liquids used in the study could be recycled three times without apparent loss in activity.

Engineering of glucoside acceptors for the regioselective synthesis of β-(1→3)-disaccharides with glycosynthases

Glycosynthase mutants obtained from Thermotoga maritima were able to catalyze the regioselective synthesis of aryl β-d-Galp-(1→3)-β-d-Glcp and aryl β-d-Glcp-(1→3)-β-d-Glcp in high yields (up to 90 %) using aryl β-d-glucosides as acceptors. The need for an aglyconic aryl group was rationalized by molecular modeling calculations, which have emphasized a high stabilizing interaction of this group by stacking with W312 of the enzyme. Unfortunately, the deprotection of the aromatic group of the disaccharides was not possible without partial hydrolysis of the glycosidic bond. The replacement of aryl groups by benzyl ones could offer the opportunity to deprotect the anomeric position under very mild conditions. Assuming that benzyl acceptors could preserve the stabilizing stacking, benzyl β-d-glucoside firstly assayed as acceptor resulted in both poor yields and poor regioselectivity. Thus, we decided to undertake molecular modeling calculations in order to design which suitable substituted benzyl acceptors could be used. This study resulted in the choice of 2-biphenylmethyl β-d-glucopyranoside. This choice was validated experimentally, since the corresponding β-(1→3) disaccharide was obtained in good yields and with a high regioselectivity. At the same time, we have shown that phenyl 1-thio-β-d-glucopyranoside was also an excellent substrate leading to similar results as those obtained with the O-phenyl analogue. The NBS deprotection of the S-phenyl group afforded the corresponding disaccharide quantitatively.

Solid-liquid phase transfer catalyzed novel glycosylation reaction of phenols

A facile and mild glycosylation reaction in solid-liquid two-phase system (powdered K2CO3/CHCl3) containing phase transfer catalyst was found to be efficient for preparation of glucosides of 2', 6'-dihydroxyacetophenone (1) and other various substituted phenols.

Reliable method for the synthesis of aryl β-D-glucopyranosides, using boron trifluoride-diethyl ether as catalyst

Stereospecific formation of aryl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosides was achieved by reaction of penta-O-acetyl-β-D-glucose 1 with substituted phenols in the presence of boron trifluoride. Yields of the purified products varied from 52-85%. Benzyl alcohol could also be glucosylated using similar conditions. All products were purified by crystallization from ethanol. The purity and the anomeric configuration of the products were determined by means of 1H and 13C NMR spectroscopy, melting points and optical rotation.