Gram scale production of 1-azido-β-d-glucose via enzyme catalysis for the synthesis of 1,2,3-triazole-glucosides

Abstract

The retaining β-glucosidase acid/base mutant TxGH116D593A catalyzed the production of 1-azido-β-d-glucose for synthesis of 15 1,2,3-triazole β-glucosyl derivatives.

Chemoenzymatic and Protecting-Group-Free Synthesis of 1,4-Substituted 1,2,3-Triazole-α-d-glucosides with Potent Inhibitory Activity toward Lysosomal α-Glucosidase

“…Protected N -Boc-propargylamine ( 1j ) was synthesized from propargylamine by reacting with (Boc) 2 O and triethylamine (Et 3 N), while 1j combined with αGA1 by applying the above conditions (Method A) afforded AGT11 in 66% yield as a white solid. Our previous experience showing that phenyl acetylenes ( 1b , 1d ) have poor reactivity with unprotected glucosylazide directed us not to follow up the above reaction conditions for these.…”

“…25−28 Recently, our group reported the gram-scale production of 1azido-β-D-glucose via using a retaining β-glucosidse acid/basemutant enzyme as the catalyst and utilized it for the synthesis of 1,2,3-triazole-β-D-glucosides, including a glucosyl Aza-BODIPY dye for enhanced photodynamic cancer therapy applications. 29,30 However, the synthesis and bioactivities of α-D-glucosylazide and its triazole glycosides are less well explored, due to the lack of easy synthetic routes. Only a few synthetic methods have been developed for the synthesis of pure α-D-glucosylazide (Figure 1A) or its mixture with βconfigured 1-azido-D-glucose via a protection strategy of several steps, and this was subsequently utilized for the synthesis of triazole-α-D-glucosides and α-D-glucosylamides.…”

“…The catalytic transglycosylation reaction has been well studied and significantly utilized in the production of several useful glycosides, i.e., ester-glycosides, flavonoid-glycosides, , and α/β-azido-glycosides. ,,,, Several synthetic routes were reported for the synthesis of 1-azido-β -d -glucose (also called β- d -glucosylazide) and well utilized in the area of bioconjugation via click chemistry. , Numerous copper- and organocatalytic-mediated click reactions were reported in the multidisciplinary chemistry research field. − Recently, our group reported the gram-scale production of 1-azido-β -d -glucose via using a retaining β-glucosidse acid/base-mutant enzyme as the catalyst and utilized it for the synthesis of 1,2,3-triazole-β- d -glucosides, including a glucosyl Aza-BODIPY dye for enhanced photodynamic cancer therapy applications. , However, the synthesis and bioactivities of α- d -glucosylazide and its triazole glycosides are less well explored, due to the lack of easy synthetic routes. Only a few synthetic methods have been developed for the synthesis of pure α- d -glucosylazide (Figure A) or its mixture with β-configured 1-azido- d -glucose via a protection strategy of several steps, and this was subsequently utilized for the synthesis of triazole-α- d -glucosides and α- d -glucosylamides. − One set of such triazole-α- d -glucosides exhibited weak inhibition against yeast α-glucosidase and rabbit muscle glycogen phosphorylase b …”

Cu(I)-Catalyzed Click Chemistry in Glycoscience and Their Diverse Applications

“…Although azido sugars were easily obtained in analytical scale via the enzymatic route simply through verifying the catalytic mutations of the preserving glycosidase, the protocol is of limited use for scale-up synthesis. Recently, Gorantla and co-workers reported a gram-scale synthesis of glycosyl azide, for example, 1-azido-β- d -glucose from p -nitrophenyl-β- d -glucopyranoside ( p NPGlc) by utilizing Thermoanaerobacterium xylanolyticus GH116 β-glucosidase ( Tx GH116D593A) in aqueous media . Thus, p NPGlc upon treatment with NaN 3 in aqueous MES buffer (pH 5.5) at 55 °C and catalytic acid/base mutant of TxGH116D593A gave the respective 1-azido-β- d -glucose in 96% yield via a transglycosylation reaction.…”

“…Thus, p NPGlc upon treatment with NaN 3 in aqueous MES buffer (pH 5.5) at 55 °C and catalytic acid/base mutant of TxGH116D593A gave the respective 1-azido-β- d -glucose in 96% yield via a transglycosylation reaction. The resultant azide was further reacted with diverse alkynes under CuAAC conditions to produce high-to-excellent yields of the required triazole-appended glycoconjugates …”