C-glycosylation reactions of sulfur-substituted glycosyl donors: evidence against the role of neighboring-group participation.

Nucleophilic substitution reactions of C-4 sulfur-substituted tetrahydropyran acetals revealed that neighboring-group participation does not control product formation. Spectroscopic evidence for the formation of an intermediate sulfonium ion is provided, as are data from nucleophilic substitution reactions demonstrating that products are formed from oxocarbenium ion intermediates. The selectivity was not sensitive to solvent or to which Lewis acid was employed. The identity of the heteroatom at the C-4 position also did not significantly impact diastereoselectivity. Consequently, neighboring-group participation was not responsible for the formation of either the major or the minor products. These studies implicate a Curtin-Hammett kinetic scenario in which the formation of a low-energy intermediate does not necessitate its involvement in the product-forming pathway.

Nucleophilic substitution reactions of sulfur-substituted cyclohexanone acetals: an analysis of the factors controlling stereoselectivity.

The reactions of cyclohexanone acetals substituted with thiophenyl groups (and other heteroatoms) at C-2 demonstrate the powerful influence that these substituents have on the stereoselectivity of nucleophilic substitution reactions. The trans selectivities of these reactions correlate with the behavior of the corresponding ketones. These experiments lend support to the possibility that the reactions of the acetals, which proceed via oxocarbenium ions, are operating under Felkin-Anh control.

NR2B-selective N-methyl-D-aspartate antagonists: synthesis and evaluation of 5-substituted benzimidazoles.

Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.