Promoter‐Controlled Synthesis and Conformational Analysis of Cyclic Mannosides up to a 32‐mer

Abstract

Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra‐large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter‐controlled cycloglycosylation approach for the synthesis of cyclic α‐(1→6)‐linked mannosides up to a 32‐mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)‐ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra‐large cyclic transition state, providing a cyclic 32‐mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2‐mer, 4‐mer, 8‐mer, 16‐mer, and 32‐mer mannosides adopted different conformational states and shapes.

Block Synthesis and Step-Growth Polymerization of C-6-Sulfonatomethyl-Containing Sulfated Malto-Oligosaccharides and Their Biological Profiling

“…It is important to note that polymerization of compound 8 enables the production of not only linear but also cyclic oligomers in a one-pot reaction, similarly to literature cyclooligomerizations observed in the polyglycosylation reactions of thioglycosides acting as both glycosyl donors and acceptors [ 32 , 33 , 34 , 35 ].…”

Synthesis of Cyclic β-1,6-Oligosaccharides by Electrochemical Polyglycosylation of glucosamine monomers

“…Therefore, electrochemical polymerizations can be utilized selective synthesis. Cyclic oligosaccharides are important class of host molecules and some natural cyclic oligosaccharides are produced by enzymatic processes; however, their chemical syntheses are still primitive [6][7][8][9][10]. We have been interested in preparation of cyclic oligosaccharides under electrochemical conditions and electrochemical conversion of linear oligosaccharides of glucosamine into the corresponding cyclic oligosaccharides by intramolecular glycosylation (Figure 1a) [11].…”

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

“…Cyclic oligosaccharides are an important class of host molecules, and some natural cyclic oligosaccharides are produced by enzymatic processes. However, the corresponding chemical syntheses are still primitive [6][7][8][9][10]. Thus, chemical glycosylation has to be improved to be able to synthesize complex oligosaccharides, including cyclic oligosaccharides.…”