Glycosidic Bond Expanded Cyclic Oligosaccharides: Synthesis and Host–Guest Binding Property of a Cyclic Pentasaccharide

Abstract

A new cyclic pentasaccharide comprising an oxymethylene glycosidic bond connecting the individual α- d -glycopyranoside monomers is synthesized through cycloglycosylation of a linear pentasaccharide precursor, which, in turn, is synthesized through the block glycosylation method. Molecular modeling shows that the 30-membered macrocyclic pentasaccharide is a distorted ellipsoid structure, with the lower and upper rims occupied by secondary and primary hydroxyl groups, respectively. Following the synthesis, the microenvironment of the cyclic pentasaccharide is assessed through thermodynamic evaluation upon complexation with 1-aminoadamantane in an aqueous solution, which shows the formation of ∼1:2 host-to-guest complex and a binding affinity of 10 500 (±425) M –1 . Synthesis and assessment of the host–guest binding property of the new glycosidic bond expanded cyclic pentasaccharide are presented.

Display of Rich Reactivities of Endo‐ and Exocyclic Unsaturated Sugars that Parallel the Native Sugars

“…Thus, glycosylation of the disaccharide acceptor with trisaccharide thioglycoside donor led to securing the linear pentasaccharide, in a good yield. Further transformations at the reducing and non‐reducing ends led to secure the AB‐type monomers of the linear tri‐ (n=2) and pentasaccharides (n=4) [52,53] …”

“…ESI‐mass spectrometric analysis suggested cyclic hexamer and nonamer formation also, however, efforts of chromatographic isolation was not successful for these higher macrocycles. The cyclization of the linear pentamer and subsequent deprotection of benzyl moieties afforded the cyclic pentasaccharide 64 (Scheme 9), apart from hydrolyzed pentasaccharide lactol monomer [48,51‐54] …”

“…Further transformations at the reducing and non-reducing ends led to secure the AB-type monomers of the linear tri-(n = 2) and pentasaccharides (n = 4). [52,53] Under the glycosylation conditions, the linear trisaccharide monomer (n = 2) provided the intramolecular glycosylation product, namely, cyclic trisaccharide 62, secured upon further deprotections of the protecting groups, as the major product. ESI-mass spectrometric analysis suggested cyclic hexamer and nonamer formation also, however, efforts of chromatographic isolation was not successful for these higher macrocycles.…”

“…The cyclization of the linear pentamer and subsequent deprotection of benzyl moieties afforded the cyclic pentasaccharide 64 (Scheme 9), apart from hydrolyzed pentasaccharide lactol monomer. [48,[51][52][53][54] The glycosidic bond-expanded cyclic di-, tri-, tetra-and pentasaccharides represent very few of the known small-ring cyclic oligosaccharides known so far. [18] The elegant work of Yamada and co-workers demonstrate that small-ring cyclic oligosaccharide would require to overcome steric barriers and strategies, such as, altered conformation of the monomers is essential in order to enforce cyclization to small-ring cyclic oligomers.…”

“…The conformations of the macrocycles were elucidated through molecular dynamic (MD) simulations and single crystal X-ray structural determinations. [52,53] Early MD simulations suggested that the pyranosides preferred the chair conformation, as that seen in naturally-occurring cyclodextrins (CDs). Subsequent X-ray structural determinations revealed the same preferred conformation to the pyranoside moieties.…”