Unusual triflic acid-promoted oligomerization of arabinofuranosides during glycosylation.

We discovered an unusual triflic acid-promoted oligomerization of arabinofuranosides during glycosylation of the primary hydroxy group of α-(1 → 5)-linked tetraarabinofuranoside bearing 4-(2-chloroethoxy)phenyl aglycone with α-(1 → 5), β-(1 → 2)-linked tetraarabinofuranoside containing N-phenyltrifluoroacetimidoyl leaving group, which led to octa-, dodeca- and hexadecaarabinofuranosides. The possible mechanism of triflic acid-promoted oligomerization was proposed. The choice of promoter was found to be a critical factor for the discovered oligomerization of arabinofuranosides.

Comparison of glycosyl donors: a supramer approach.

The development of new methods for chemical glycosylation commonly includes comparison of various glycosyl donors. An attempted comparison of chemical properties of two sialic acid-based thioglycoside glycosyl donors, differing only in the substituent at O-9 (trifluoroacetyl vs chloroacetyl), at different concentrations (0.05 and 0.

Quantum Mechanical-Cluster Approach to Solve the Bioisosteric Replacement Problem in Drug Design.

Bioisosteres are molecules that differ in substituents but still have very similar shapes. Bioisosteric replacements are ubiquitous in modern drug design, where they are used to alter metabolism, change bioavailability, or modify activity of the lead compound. Prediction of relative affinities of bioisosteres with computational methods is a long-standing task; however, the very shape closeness makes bioisosteric substitutions almost intractable for computational methods, which use standard force fields.

Exhaustive Conformational Search for Sialyl Cation Reveals Possibility of Remote Participation of Acyl Groups.

Finding convenient ways for the stereoselective α-sialylation is important due to the high practical significance of α-sialic acid-containing glycans and neoglycoconjugates. It was proposed that sialylation stereoselectivity is determined by the structure of the sialyl cation (also known in biochemistry as "sialosyl cation"), a supposed intermediate in this reaction. Here we design a new approach for studying the conformational space of highly flexible sialyl cation and find 1625 unique conformers including those stabilized by covalent remote participation (also known as long-range participation) of 4-O-acetyl (4-OAc), 5-N-trifluoroacetyl (5-NTFA), as well as 7,8,9-OAc from both α and β sides.

Redirecting a Diels-Alder Reaction toward (2 + 2)-Cycloaddition.

Recently, reactions of allylidenhydrazones with tetracyanoethylene were found to lead to cyclobutanes-products of usually unfavorable (2 + 2) cycloaddition. Herein we computationally demonstrate that the (4 + 2) product of this reaction is severely destabilized by incomplete C-N bond formation, arising from a complex interplay of substituent electronic effects. We show how destabilization of a single bond in the front-runner product averts its formation and redirects chemical reaction toward an uncharacteristic pathway.

Arabinofuranose 1,2,5-orthobenzoate as a single precursor of linear α(1 → 5)-linked oligoarabinofuranosides.

Selectively protected mono-, di- and trisaccharide thioglycoside building blocks with unprotected primary hydroxy group at the non-reducing end, available in only one step from 3-O-benzoyl β-d-arabinofuranose 1,2,5-orthobenzoate, were used in the synthesis of linear α(1 → 5)-linked oligoarabinofuranosides up to octasaccharide. The obtained oligosaccharides contain 4-(2-chloroethoxy)phenyl (CEP) or 4-(2-azidoethoxy)phenyl (AEP) pre-spacer aglycons that allow preparation of neoglycoconjugates.

Stereoselective sialylation with O-trifluoroacetylated thiosialosides: hydrogen bonding involved?

A series of novel sialyl donors containing O-trifluoroacetyl (TFA) groups at various positions was synthesized. The choice of protecting groups in sialyl donors was based on hypothesis that variations in ability of different acyl groups to act as hydrogen bond acceptors would influence the supramolecular structure of reaction mixture (solution structure), hence the outcome of sialylation. These glycosyl donors were examined in the model glycosylation of the primary hydroxyl group of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose in comparison with sialyl donors without O-TFA groups.