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The synthesis of the tetrasaccharide repeating unit of the O-antigen of Escherichia coli O163 as its p-methoxyphenyl (PMP) glycoside was achieved followed by sequential glycosylation strategy through thioglycoside activation using sulfuric acid immobilized on silica (H 2 SO 4 -silica) in conjunction with N-iodosuccinimide as a Brønsted acid catalyst. The application of one-pot reaction conditions for two glycosylations and in situ PMB-group removal reduced the number of reaction steps significantly. The L-QuipNAc building block was obtained from known carbohydrate L-rhamnose precursors. The stereoselective outcomes of all glycosylation reactions were found to be very good. A late-stage TEMPO-mediated oxidation was performed for the formation of required uronic acid moiety. An analogue of the target tetrasaccharide was also prepared by using one-pot glycosylation approach. Such synthetic oligosaccharides could later be effectively conjugated with an appropriate protein to furnish glycoconjugate derivatives for their use in immunochemical studies.

Recent studies have shown the involvement of GluN2A subunit‐containing NMDA receptors in various neurological and pathological disorders. In the X‐ray crystal structure, TCN‐201 (1) and analogous pyrazine derivatives 2 and 3 adopt a U‐shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π‐interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane (5) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7, triazole 10 and benzamides 12. The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two‐electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o‐iodobenzamide 12 b with the highest similarity to TCN‐201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN‐201 (1). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN‐201 binding site.

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