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The Z and E isomers of 3-[4-(dimethylamino)phenyl]-2-(2,4,6-tribromophenyl)acrylonitrile, C17H13Br3N2, ( 1), were obtained simultaneously by a Knoevenagel condensation between 4-(dimethylamino)benzaldehyde and 2-(2,4,6-tribromophenyl)acetonitrile, and were investigated by X-ray diffraction and density functional theory (DFT) quantum-chemical calculations. The ( Z)-( 1) isomer is monoclinic (space group P21/ n, Z′ = 1), whereas the ( E)-( 1) isomer is triclinic (space group P, Z′ = 2). The two crystallographically-independent molecules of ( E)-( 1) adopt similar geometries. The corresponding bond lengths and angles in the two isomers of ( 1) are very similar. The difference in the calculated total energies of isolated molecules of ( Z)-( 1) and ( E)-( 1) with DFT-optimized geometries is ∼4.47 kJ mol−1, with the minimum value corresponding to the Z isomer. The crystal structure of ( Z)-( 1) reveals strong intermolecular nonvalent Br...N [3.100 (2) and 3.216 (3) Å] interactions which link the molecules into layers parallel to (10). In contrast, molecules of ( E)-( 1) in the crystal are bound to each other by strong nonvalent Br...Br [3.5556 (10) Å] and weak Br...N [3.433 (4) Å] interactions, forming chains propagating along [110]. The crystal packing of ( Z)-( 1) is denser than that of ( E)-( 1), implying that the crystal structure realized for ( Z)-( 1) is more stable than that for ( E)-( 1). [ABSTRACT FROM AUTHOR]

The primary purpose of this work was to demonstrate the suitability of circular dichroism (CD) spectroscopy in stereochemical studies of α,β-unsaturated oximes, with particular emphasis on determination of E and Z geometry of the oxime double bond. As models for this study, O-phenyl and O-triphenylmethyl (trityl) oximes of 4-hydroxy-2-methylcyclopent-2-en-1-one were selected. These model compounds differ in both absolute configuration at C4 carbon atom and E- Z configuration of the oxime double bond. The basic dichroic technique applied was electronic circular dichroism (ECD) assisted by quantum-chemical calculations and vibrational circular dichroism (VCD) for selected cases. Such an approach enabled effective implementation of both goals. Thus, we were able to associate the signs of Cotton effects in the range of 190-240 nm with the absolute configuration at C4 and within 240-300 nm with the E- or Z-geometry of the oxime double bond. Within this work, optical activity of the protecting trityl group was also studied towards formation of the propeller-shaped conformations by using the same combined CD/DFT methodology. As shown, the helical structure of the trityl group has a considerable influence on the ECD spectra. However, the MPM and PMP conformers of the trityl group are in fact almost equally populated in the conformational equilibrium, making it impossible to distinguish them. On the other hand, rotamers of the hydroxyl group at C4 show a decisive impact on the VCD spectra in both phenoxy and trityl oximes. [ABSTRACT FROM AUTHOR]

Abstract: Amidines, the nitrogen analogues of carboxylic acids, show interesting roles as pharmacophore groups in biologically active agents and in compounds of pharmaceutical interest. In the last years, our research group disclosed inhibitors of inducible and neuronal Nitric Oxide Synthase (iNOS and nNOS, respectively) containing the amidino moiety, with the aim to extend the study of the possible ligand‐enzyme interactions. Here we discuss the synthesis and spectral studies of acetamidino derivative N‐(2‐(pyrrolidin‐1‐yl)ethyl)acetimidamidinium bromide, and how these studies led us to identification of a E/Z configurational change, which could be helpful in elucidating the ligand‐enzyme interactions. [ABSTRACT FROM AUTHOR]

A convergent, general synthetic route to 17-membered macrocycles was developed to support biological evaluation and structure–activity relationship (SAR) studies during phenotypic screening for immunology targets. A series of amide coupling reactions led to a ring-closing metathesis (RCM) precursor that was cyclized using Grubbs' catalysts. It was found that the reaction formed the macrocyclic products in a 3:1 ratio of E/Z isomers. Moreover, it was shown that a number of similarly substituted RCM precursors undergo cyclization to produce the geometric E/Z isomers in roughly the same 3:1 ratio. The remarkable independence of the E/Z outcome from the substitution pattern of the RCM precursor makes this synthetic approach generally applicable. Separation of the E/Z isomers was achieved by preparative high-performance liquid chromatography and allowed biological profiling of the geometric isomers. Reactive groups in the macrocycle were utilized for late-stage modifications in the fashion of diversity-orientated synthesis (DOS), yielding analogs for SAR studies. [ABSTRACT FROM AUTHOR]