Structure and conformation of heterocycles—VIII : Peripherally substituted 1,4,5,8-tetraoxadecalins

The synthesis of the title compounds was examined and a mechanistic scheme was put forward, which accounts for their formation along with higher substituted by-products and with the corresponding bidioxolan-2-yl isomers.Chemical correlation between two members of the series, trans -2,3-dicarbomethoxy- and trans-2, 3 - dimethyl - tetraoxadecalin, was performed.All stereoisomeric 2,3 - dicarbomethoxy -1,4,5,8- tetraoxadecalins were prepared and chemically equilibrated. The free energy differences at 65° between them were thus obtained. This led to an evaluation of the conformational free energy of the carbomethoxy group in dioxanes, ΔG_CO2Me^o. = 0.38 kcal/mole.Dynamic conformational analysis by variable temperature NMR measurements on cis - 2, 3 -dicarbomethoxy - anti -cis - 1, 4, 5, 8- tetraoxadecalin led to a ring inversion barrier of AG₁₉₃^≠ = 10.0 kcal/mole.     

DFT,solution, and crystal conformation of eremophilanolides

The minimum energy conformation of five eremophilanolides (1–5) from the tubercles of Psacalium paucicapitatum was calculated using density functional theory (DFT) at the B3LYP/6-31G¹ level. Comparison of the experimental ¹H–¹H coupling constant values of 1–5 with those generated employing a generalized Karplus-type relationship using dihedral angles extracted from the DFT calculation and from the crystal structures for 1 and 3–5 shows good agreement. The A ring of 1–5 adopts an almost perfect chair conformation with the Me-14 group in an axial position and the Me-15 in an equatorial position.     

Configurational and conformational analysis Axial-axial and axial-equatorial coupling constants in six-membered ring compounds

Axial-axial and axial-equatorial coupling constants (J_aa and J_ae) have been obtained directly from the NMR spectra of simple AB systems in a number of cis- and trans-l-(substituted)-2-arylcyclohexanes-3,3,6,6-d₄ measured in several solvents. Variations in J_aa and J_ae have been observed with various substituents. No simple correlation is found between electronegativity of substituents and substituent effects on coupling constants. A review of J_aa and J_ae in six-membered ring compounds is given.     

Theoretical conformational analysis of substituted nitroethenes in solution

Theoretical conformational analysis of 1-nitro- and 1-bromo-1-nitro-2-(trichloromethyl)ethenes dissolved in methylene chloride and benzene was carried out by the B3LYP/6-31G* method. The calculated structures of these compounds were found to nicely fit experiment: Both in the gas phase and in solution, 1-nitro-(2-trichloromethyl)ethene is an E isomer, while its bromine-containing analog is a Z isomer.     

Reactivities of carboxyalkyl-substituted 1,4,5,8-naphthalene diimides in aqueous solution

A series of water-soluble 1,4,5,8-naphthalene diimide derivatives has been prepared and their redox and photophysical properties characterized. From laser flash photolysis studies, the triplet excited state of N,N'-bis[2-(N-pyridinium)ethyl]-1,4,5,8-naphthalene diimide (NDI-pyr) was found to undergo oxidative quenching with the electron donors DABCO, tyrosine, and tryptophan as expected from thermodynamics. Interestingly, the reactivities of naphthalene diimides (NDI) possessing alpha- and beta-carboxylic acid substituents (R = -CH2COO-, -C(CH3)2COO-, and -CH2CH2COO-) were strikingly different. In these compounds, the transient produced upon 355 nm excitation did not react with the electron donors. Instead, this transient reacted rapidly (k > 10(8)-10(9) M-1 s-1) with known electron acceptors, benzyl viologen and ferricyanide. The transient spectrum of the carboxyalkyl-substituted naphthalimides observed immediately after the laser pulse was nearly identical to the one-electron-reduced form of 1,4,5,8-naphthalene diimide (produced independently using the bis-pyridinium-substituted naphthaldiimide). From our studies, we conclude that the transient produced upon nanosecond laser flash photolysis of NDI-(CH2)nCOO- is the species produced upon intramolecular electron transfer from the carboxylate moiety to the singlet excited state of NDI. In separate experiments, we verified that the singlet excited state of NDI-pyr does, indeed, react intermolecularly with acetate, alanine, and glycine. The process is further substantiated using thermodynamic driving force calculations. The results offer new prospects of the efficient photochemical production of reactive carbon-centered radicals.     

The molecular and crystal structure of 1,2-diazepines and their conformational mobility in solution

X-ray diagrams of 1,2-diazepines showed them to be boat-shaped molecules with a localized imine double-bond. Variable temperature NMR and variable temperature CD of the optically active 1,2-diazepine (15) indicated the existence of a fast equilibrium between the two boat shaped diastereoisomeric conformations. In the iron-tricarbonyl complex (6) of the 1-isopropoxycarbonyl 1,2-diazepine (4) the seven-membered ring is bent by 40° along the C(4)–C(7) line.     

Structure determination and conformation analysis of symmetrical dimers

Conformational and stereochemical analysis of six new symmetrical dimers was performed using proton-proton vicinal coupling measured from (1)H NMR and (13)C satellites of (1)H NMR signals, natural abundance (13)C-edited nuclear overhauser effect (NOE) experiments, comprehensive NOE analysis and molecular modeling. The (13)C satellite analysis and (13)C-edited NOE experiments were carried out to extract spectral information between equivalent protons. Molecular modeling was applied for estimations of three-dimensional parameters of the studied dimers, which were subsequently used to generate a set of theoretical NOE for each possible conformation. The J-coupling, (13)C-edited NOE and quantitative NOE analyses showed the predominance of gauche conformation for three dimers, whereas a mixture of gauche and anti conformations (45:55) for three other dimers was established by quantitative NOE analysis. X-ray crystallographic study confirmed the stereochemistry of one of the dimers and revealed a discrepancy in conformation stability between liquid and solid states.     

Configurational and conformational analysis of chiral molecules using IR and VCD spectroscopies: spiropentylcarboxylic acid methyl ester and spiropentyl acetate

The chiral monosubstituted derivatives of spiropentane, spiropentylcarboxylic acid methyl ester, 1, and spiropentyl acetate, 2, have been synthesized in optically active form. Configurational and conformational analysis of 1 and 2 has been carried out using infrared (IR) and vibrational circular dichroism (VCD) spectroscopies. Analysis of the experimental IR and VCD spectra has been carried out using ab initio density functional theory (DFT). For both 1 and 2, DFT predicts two populated conformations. Comparison to experiment of the conformationally averaged IR and VCD spectra of 1 and 2, predicted using DFT, provides unequivocal evidence of the predicted conformations and yields the absolute configurations R(-)/S(+) for 1 and R(+)/S(-) for 2. These absolute configurations are consistent with the R(-)/S(+) absolute configuration of spiropentylcarboxylic acid, assigned previously via X-ray crystallography of its alpha-phenylethylammonium salt.     

Structure and conformation of DAB dendrimers in solution via multidimensional NMR techniques.

NOESY-HSQC 3D-NMR and NOESY 2D-NMR techniques have been used on a 750 MHz spectrometer to study the chain conformations of different generation DAB dendrimers (poly[propylene imine] dendrimers) in chloroform and benzene solutions. The high-field multidimensional NMR techniques provided the chemical shift dispersion needed to resolve all of the unique resonances in the dendrimers. By studying the NOE interactions among dendritic chain protons, information about through space interactions between protons on different parts of the dendrimer chain is obtained, which is directly related to the conformation of the dendrimer. These experiments also give further proof of the chemical shift assignments obtained from the HMQC-TOCSY 2D and 3D NMR experiments. The concentration effects on chemical shifts have also been observed, revealing information about the interactions between solvent and different parts of dendrimer molecules. These studies clearly show for DAB dendrimers, that folded chain conformations can occur in nonpolar solvents such as benzene and extended chain conformations are predominant in polar solvents such as chloroform.     

Structure and conformation of heterocycles. 13. conformational analysis of 2,3-DI(R)OXY-1,4-dioxanes: anomeric and gauche effects

A series of $\text{trans}$- and $\text{cis}$-2,3-di R)oxy-1,4-dIoxanes (R = Me,Ph, Ac) and some 2,5-disubstituted analogis were prepared and analysed by various NMR techniques. The $\text{trans}$ isomers occur in more than 96% as diaxial conformers. Molecular mechanics calculations largely confirm these findings, which are interpreted -in terms of combined anomeric and gauche effects.     

Comparison of solution and crystal structures of preQ1 riboswitch reveals calcium-induced changes in conformation and dynamics

Riboswitches regulate gene expression via specific recognition of cognate metabolites by their aptamer domains, which fold into stable conformations upon ligand binding. However, the recently reported solution and crystal structures of the Bacillus subtilis preQ(1) riboswitch aptamer show small but significant differences, suggesting that there may be conformational heterogeneity in the ligand-bound state. We present a structural and dynamic characterization of this aptamer by solution NMR spectroscopy. The aptamer-preQ(1) complex is intrinsically flexible in solution, with two regions that undergo motions on different time scales. Three residues move in concert on the micro-to-millisecond time scale and may serve as the lid of the preQ(1)-binding pocket. Several Ca(2+) ions are present in the crystal structure, one of which binds with an affinity of 47 ± 2 μM in solution to a site that is formed only upon ligand binding. Addition of Ca(2+) to the aptamer-preQ(1) complex in solution results in conformational changes that account for the differences between the solution and crystal structures. Remarkably, the Ca(2+) ions present in the crystal structure, which were proposed to be important for folding and ligand recognition, are not required for either in solution.     

Mechanism of 1,4,5,8-naphthalene tetracarboxylic acid dianhydride hydrolysis and formation in aqueous solution

The study of highly conjugated, carbonyl-containing molecules such as 1,4,5,8-naphthalene tetracarboxylic dianhydride, III, is of interest since reactivity differences and transmission of electronic effects through the conjugated framework can be evidenced. The kinetics of hydrolysis of III in aqueous solution were determined from 5 M acid to pH 10. In basic solution hydrolysis of III yields, sequentially, 1,4,5,8-naphthalene diacid monoanhydride, II, and 1,4,5,8-naphthalene tetracarboxylic acid, I. The second order rate constant for alkaline hydrolysis is 200 fold higher for the first ring opening. The water-catalyzed hydrolysis of III yields a pH-dependent mixture of ionic forms of I and II. The rate constant for water-catalyzed hydrolysis of III is 25 fold higher than that for II. In concentrated acid the rates for reaching equilibrium (I, II and III) increase and III is the major product. The pK(a)s of I (3.24, 5.13 and 6.25) and II (3.05, 5.90) were determined by potentiometric, fluorescence and UV spectroscopy titrations and by quantitative fit of the kinetic and equilibrium data. The apparent, pH-dependent, equilibrium constants, K(EqII), for anhydride formation between I and II were obtained from the UV spectra. The quantitative fit of kinetic and equilibrium data are consistent with the assumption that anhydride formation only proceeds with the fully protonated species for both I and II and permitted the estimation of the equilibrium constants for anhydride formation, K(EqII). The value of K(EqII) (I <==> II) between pH 1 and 6 was ca. 5. Geometry optimization calculations in the gas phase of the reactions of III in alkaline, neutral and acid conditions, at the DFT level of theory, gave electronic distributions that were qualitatively consistent with the experimental results.     

Structure elucidation and conformational analysis of a fused cyclopentanopyrazolidinol

From the reaction of 2‐acetylcyclopentanone with benzoylhydrazine, the cyclopentanopyrazole derivative 4 was obtained as the only product. The structural assignment of this compound and also of the hydroxypyrazoline 3 , used as a model compound, was established by analysis of their NMR spectra (¹H, ¹³C, COSY, NOESY, HETCOR and COLOC). Copyright © 2002 John Wiley & Sons, Ltd.