Hydrogen-Bond-Mediated Aglycone Delivery: Synthesis of β-d-Fructofuranosides

Abstract

The construction of β-D-fructofuranosidic linkages is one of the major challenges in carbohydrate chemistry. In this work, we developed an efficient method for the synthesis of β-D-fructofuranosides by using a 6-picoloyl-protected fructofuranosyl thioglycoside as the glycosyl donor. Subsequently, we applied the approach to a wide variety of donors and acceptors. Furthermore, the successful synthesis of levantetrose confirmed its applicability in the multistep synthesis of oligosaccharides.

Influence of Remote Picolinyl and Picoloyl Stereodirecting Groups for the Stereoselective Glycosylation

“…To explain the applicability of this approach, they synthesized the protected non-reducing terminal octasaccharide capping motif of mycobacterial LAM. [54] For that, they treated Similarly, Zhongjun Li and his co-worker [55] extended the scope of picoloyl protected donors by synthesizing β-Dfructofuranosides from 6-picoloyl-protected fructofuranosyl thioglycoside 161 via Hydrogen-Bond-Mediated Aglycone Delivery using DBDMH as a promoter. For studying the substrate scope of this reaction, the glycosylation to a wide range of substrates including primary hydroxyl acceptors as well as simple secondary alcohol acceptors was performed to figure out the repercussion of different types of substitutions present at different positions in the glycosyl donors on the glycosylation and as expected the corresponding disaccharide (162 a-f) were obtained in high yields with excellent β-stereoselectivity However, the glycosylation with secondary glycosyl acceptor 162 e gave the corresponding disaccharide in low yield (< 30%) (Scheme 37).…”

“…The same steps was repeated and after two glycosylations, levantetrose 166 was produced in 75% yield with high β‐Stereoselectivity (Scheme 39). [55] …”

“…Finally, they proposed the mechanism of the studied glycosylation reaction as shown in scheme 38, according to which firstly the sp 2 ‐hybridized nitrogen of 6‐picoloyl‐protected fructofuranosyl thioglycoside donor formed a temporary hydrogen bond with acceptor and then undergo activation followed by nucleophilic attack via syn‐fashion with respect to the picoloyl group to the anomeric center of the donor 161 to give the designed product 162 stereoselectively [55] . However, it is an anticipated mechanism, there is no significant proof or explanation for the formation of H‐bond before activation of the donor are provided.…”

2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

“…Although they observed decreased stereoselectivity when electron-deficient or bulky acceptors were glycosylated, 39 this elegant strategy has been successfully applied to prepare various glycosides including -sialic glycosides. [40][41][42][43][44][45][46][47][48] Another N-heterocyclic 2-quinolinecarbonyl group was employed by Yang and coworkers as H-bond-acceptor to effectively construct -arabinofuranosides and /-Kdo glycosides. 49,50 H-bonding also played an important role in several reagentcontrolled strategies for -glycosylation using -glycosyl donors or intermediates (Fig.…”

2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

“…Although they observed decreased stereoselectivity when electron-deficient or bulky acceptors were glycosylated, 39 this elegant strategy has been successfully applied to prepare various glycosides including -sialic glycosides. [40][41][42][43][44][45][46][47][48] Another N-heterocyclic 2-quinolinecarbonyl group was employed by Yang and coworkers as H-bond-acceptor to effectively construct -arabinofuranosides and /-Kdo glycosides. 49,50 H-bonding also played an important role in several reagentcontrolled strategies for -glycosylation using -glycosyl donors or intermediates (Fig.…”