Conformational isomerism

About: Conformational isomerism is a research topic. Over the lifetime, 11563 publications have been published within this topic receiving 199312 citations.

Conformational analysis of two cyclic analogs of angiotensin: implications for the biologically active conformation.

Abstract: Conformations of two cyclic analogs of angiotensin (Asp1-Arg2-Val3-Tyr4-Val/Ile5-His6-Pro7-Phe8, AT), cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT, were studied, independently employing two complementary techniques, energy calculations and NMR measurements in DMSO solution. NMR data were indicative of well-defined solution conformations for the cyclic moieties of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT, including the phi values for the Cys3/HCys3 and Tyr4 residues, as well as the chi 1 value for the Tyr4 residue. Solution conformations for the exocyclic linear parts of both molecules cannot be described by the NMR data with the same precision. At the same time, independent energy calculations revealed the same conformations of cyclic moieties of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT among low-energy conformers for both peptides. Moreover, the same conformations are compatible with the model of AT receptor-bound conformation (Nikiforovich & Marshall, 1993), which assumes the particular spatial arrangement of aromatic moieties of Tyr4, His6, and Phe8 residues and the C-terminal carboxyl. These conformers of cyclo[Sar1, Cys3, Mpt5]-AT and cyclo[Sar1, HCys3, Mpt5]-AT contain "an open turn" in the backbone of the Tyr4-Val5 residues, instead of the earlier proposed beta-like reversal, thus confirming the suggestion that the conformation(s) ensuring binding of AT analogs with specific receptors should not be described in terms of a unique backbone conformer.

Theoretical Study on 1,2-Dihydroxybenzene and 2-Hydroxythiophenol: Intramolecular Hydrogen Bonding

Abstract: The molecular structures and the intramolecular hydrogen bonding for 1,2-dihydroxybenzene and 2-hydroxythiophenol have been precisely investigated by an ab initio method and density functional theory (DFT) We have considered the several possible conformations with different types of intramolecular hydrogen bonding in given molecules to understand the nature of the hydrogen bonding among these conformers The optimized geometrical parameters for conformer 1a at the B3LYP levels as well as the computed 1H NMR chemical shifts for conformer 2b at the RHF/6-31+G*//B3LYP/6-31+G* level are in good agreement with previous experimental results It is confirmed from these results that the inclusion of electron correlation is crucial to elucidate molecular properties for the intramolecular hydrogen bonding systems We have also compared the molecular energies between two different conformations both with a hydrogen bond and with no hydrogen bond of a given molecule In 1,2-dihydroxybenzene, the energy stabilized by

Experimental and Theoretical Conformational Analysis of 5-Benzylimidazolidin-4-one Derivatives – a ‘Playground’ for Studying Dispersion Interactions and a ‘Windshield-Wiper’ Effect in Organocatalysis

Abstract: The PF6 salts of 5-benzyl-1-isopropylidene- and 5-benzyl-1-cinnamylidene-3-methylimidazolidin-4-ones 1 (Scheme) with various substituents in the 2-position have been prepared, and single crystals suitable for X-ray structure determination have been obtained of 14 such compounds, i.e., 2-10 and 12-16 (rigs. 2-5). In nine of the structures, the Ph ring of the benzyl group resides above the heterocycle. in contact with the cis-substituent at C(2) (staggered conformation A: Figs. 1-3); in three structures, the Ph ring lies above the iminium pi-plane (staggered conformation B; Figs. 1 and 4); in two structures, the benzylic C-C bond has an eclipsing conformation (C; Figs. 1 and 5) which places the Ph ring simultaneously at a maximum distance with its neighbors, the CO group, the N=C-pi-system, and the cis-substituent at C(2) oft lie heterocycle. It is suggested by a qualitative conformational analysis (Fig. 6) that the three staggered conformations of the benzylic C-C bond are all subject to unfavorable steric interactions, so that the eclipsing conformation may lie a kind of 'escape'. State-of-the-art quantum-chemical methods, with large AO basic sets (near the limit) for the single-point calculations, were used to compute the structures of seven of the 14 iminium ions, i.e., 3, 4/12, 5-7, 13, and 16 (Table) in the two staggered conformations, A and B, with the benzylic Ph group above the ring and above the iminium pi-system, respectively. In all cases, the more stable Computed conformer ('isolated-molecule' structure) corresponds to the one present in the crystal (overlay in rig. 7). The energy differences are small (<= 2 kcal/mol) which, together with the result of a potential-curve calculation for the rotation around the benzylic C-C bond of one of the structures, 16 (Fig. 8), suggests that the benzyl group is more or less freely rotating at ambident temperatures. The importance of intramolecular London dispersion (benzene ring in 'contact' with the cis-substituent in conformation A) for DFT and other quantum-chemical computations is demonstrated; the benzyl-imidazolidinones 1 appear to be ideal systems for detecting dispersion contributions between a benzene ring and alkyl or aryl CH groups. Enylidene ions of the type studied herein are the reactive intermediates of enantioselective organocatalytic conjugate additions, Diels-Alder reactions, and many other transformations involving alpha,beta-unsaturated carbonyl compounds. Our experimental and theoretical results are discussed in view of the performance of 5-benzyl-imidazolidinones as enantioselective catalysts.

Recent synthetic approaches toward non-anomeric spiroketals in natural products.

Abstract: Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.