Daniela C. Oniciu

A novel Mannich-type reaction: Lanthanide triflate-catalyzed reactions of N-(α-aminoalkyl)benzotriazoles with silyl enolates

Abstract In the presence of a catalytic amount of a lanthanide triflate, N-(α-aminnoalkyl)benzotriazoles reacted with silyl enolates to give the corresponding β-amino ketone or ester derivatives in high yields with high diastereoselectivities.

Gear effect—10: Conformational aspects of the positive or negative buttressing effects of methyl groups: polymethylpyridines

Abstract The effect of the shape of a methyl group on reactivity, which cannot be accounted for by considering a methyl group as a spherical substituent with the appropriate van der Waals radius, was considered in kinetics of alkylalion of substituted pyridines and barriers to rotation and ground state conformations of an isopropyl group attached to a planar framework. The perturbation of a methyl group by an o-methyl group is accounted for by a unique conformational explanation which involves the polyhedral shape of the methyl group.

Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Abstract Lithiated oxazolo[3,4- a ]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4- a ]benzimidazoles 5a – d in good yields as single diastereoisomers. ( R )-Benzimidazol-2-yl carbinols 6a – d were obtained upon hydrolysis under acidic conditions of 1 H ,3 H -oxazolo[3,4- a ]benzimidazole derivatives.

P2Y13 Receptor Regulates HDL Metabolism and Atherosclerosis In Vivo

High-density lipoprotein (HDL) is known to protect against atherosclerosis by promoting the reverse cholesterol transport. A new pathway for the regulation of HDL-cholesterol (HDL-c) removal involving F1-ATPase and P2Y13 receptor (P2Y13R) was described in vitro, and recently in mice. However, the physiological role of F1-ATPase/P2Y13R pathway in the modulation of vascular pathology i.e. in the development of atherosclerotic plaques is still unknown. We designed a specific novel agonist (CT1007900) of the P2Y13R that caused stimulation of bile acid secretion associated with an increased uptake of HDL-c in the liver after single dosing in mice. Repeated dose administration in mice, for 2 weeks, stimulated the apoA-I synthesis and formation of small HDL particles. Plasma samples from the agonist-treated mice had high efflux capacity for mobilization of cholesterol in vitro compared to placebo group. In apoE−/− mice this agonist induced a decrease of atherosclerotic plaques in aortas and carotids. The specificity of P2Y13R pathway in those mice was assessed using adenovirus encoding P2Y13R-shRNA. These results demonstrate that P2Y13R plays a pivotal role in the HDL metabolism and could also be a useful therapeutic agent to decrease atherosclerosis. In this study, the up-regulation of HDL-c metabolism via activation of the P2Y13R using agonists could promote reverse cholesterol transport and promote inhibition of atherosclerosis progression in mice.

Benzotriazole-Assisted Synthesis of N-(α-Cyanoalkyl)sulfonamides

Abstract N-(α-Benzotriazol-1-ylalkyl)sulfonamides, readily available from benzotriazole, an aldehyde and a sulfonamide, are converted into the corresponding N-(α-cyanoalkyl)sulfonamides in good yields by treatment with potassium cyanide.

The Mitsunobu Reaction: An Alternative Synthesis of 1-(Primary Alkyl)benzotriazoles

Abstract 1-(Primary alkyl)benzotriazoles are obtained in convenient yields by treating the corresponding alcohol with triphenylphosphine, N-bromosuccinimide and benzotriazole. Under these conditions, the alcohols gave exclusively the corresponding 1-alkyl-benzotriazoles. Allyl and propargyl alcohols also reacted regiospecifically in a typical Sn2 manner, and no products derived from prototropic rearrangement were found.

4,6-Bis- and 2,4,6-tris-(N,N-dialkylamino)-s-triazines: synthesis, NMR spectra and restricted rotations

Syntheses of various symmetrically and non-symmetrically trisubstituted triazines are reported. Dynamic NMR (1H and 13C) experiments demonstrate that 2,4,6-tris(dialkylamino)-s-triazines show correlated rotations of the alkyl groups in the dialkylamino moieties. Unsymmetrical 2-chloro-, 2-alkoxy- and 2-aryloxy-4,6-bis(di-n-alkylamino)-s-triazines display two non-equivalent n-alkyl groups, due to the restricted rotation around the Ar–N bonds.

Study of the enol–enaminone tautomerism of α-heterocyclic ketones by deuterium effects on 13C chemical shifts

Deuterium isotope effects on 13C chemical shifts have been measured for the enol and enaminone tautomers of a series of α-heterocyclic ketones. Partial deuteration of the exchangeable hydrogen bound to the oxygen atom of the enol or the nitrogen atom of the enaminone leads to deuterium induced shifts of the 13C frequencies (2DIS) which are distinctive for the two types of structures. Thus, 9-methyl-2-phenacyl-1,10-phenanthroline, 2-pyridylacyl- and 2-phenacyl-quinazolines and 2-pyridylacyl- and 2-phenacyl-quinolines, which are known from independent evidence to exist in the enaminone structures, display large and variable negative 4DIS values, –240, –93, –126, –437 and –375, respectively, at the carbon bearing the oxygen atom. By contrast, 2-pyridylacyl- and 2-phenacyl-pyrazines, which are known to exist in the enol form, show large positive 2DIS values, 527 and 479, respectively, for the oxygen bound carbon atom.

Restricted rotations in 4,6-bis- and 2,4,6-tris-(N,N-dialkylamino)-s-triazines

Barriers to rotation have been measured in some 4,6-bis- and 2,4,6-tris-(N,N-dialkylamino)-s-triazines. X-Ray crystal structures are reported for 2-chloro-4,6-bis(diisopropylamino)-s-triazine 1,2,4,6-tris(diisopropylamino)-s-triazine 6,2,4,6-tris(diisobutylamino)-s-triazine 8 and the tetrakis(dibutylamino) derivative 12. In the isopropyl compounds 1 and 6, the structures are precisely ordered with all the isopropyl groups in the same direction: the dynamic NMR behaviour is in good agreement and barriers for rotation around the N–Ar and N–Cα bonds in 1 were assigned as 15.6 and 12.1 kcal mol–1, respectively.

Variable regioselectivity in reactions of N-lithio-N-vinylaniline with arenedicarboxylates and α,β-unsaturated esters

Regioselectivity patterns for the reactions of N-lithio-N-vinylaniline with several arenedicarboxylates and esters of α,β-unsaturated acids are reported. N-Lithio-N-vinylaniline reacted at both of its ambident anionic sites, to give β-enamino ketones and amide derivatives. A bridgehead compound resulting from cycloadditions involving N-lithio-N-vinylaniline was also formed in the reactions with ethyl cinnamate and ethyl phenylpropiolate. The structures of all compounds formed were fully characterised by NMR techniques.