Absolute configuration of C76 from optical rotatory dispersion.

The absolute configuration of C76 has been determined as (+)589-(fC)-C76 , for the first time, by comparing the experimental and predicted optical rotatory dispersion (ORD) patterns. The experimental ORD pattern was derived from the experimental electronic circular dichroism (ECD) spectrum using the Kramers-Kronig (KK) transform. The theoretical ORD spectra were calculated in the resonant region using linear response theory, and also using the KK transform of the theoretical ECD spectrum, at different theoretical levels, namely BHLYP/6-31G*, B3LYP/6-31G*, BLYP/6-31G*, and HF/6-31G*. Good agreement noted between experimental and predicted spectra allows for an unambiguous determination of the absolute configuration.     

Discussion of absolute configuration for bioactive Griseusins by comparing computed optical rotations and electronic circular dichroism with the experimental results

Absolute configurations of seven bioactive natural Griseusins were investigated. Optical rotation and electronic circular dichroism were calculated at the B3LYP/6-311++G(2d,p)//PCM/B3LYP/6-311++G(2d,p) or other levels in the gas phase and/or in solution. Computational results exhibited that the early reported absolute configuration of four among the seven may not be the best structures after comparing the computed optical rotations, electron circular dichroisms to the experimental data. Then four favorable structures are suggested based on the comparison of predicted optical rotations and electronic circular dichroisms to the experimental results. It is the first time to find that the different position of carbonyl group on aromatic ring (planar structure changes) in Griseusins can lead to the ECD curve reversed instead of the stereogenic center changes. In traditional opinion, ECD curve reversal happens only when stereogenic center configuration reverses, such as from AC of (R) to (S).     

Absolute configuration of Buagafuran:An experimental and theoretical electronic circular dichroism study

Buagafuran is a novel drug candidate derived from natural product.Its absolute configuration has been confirmed by electronic circular dichroism combined with modern quantum-chemical calculation using time-dependent density functional theory.The predicted UV absorbance peak is underestimated by several nanometers compared with the experimental data.The applicability of empirical rule for the C=C-C-O system in Buagafuran has also been discussed.Our results show that electronic circular dichroism could be a useful tool for the absolute configuration assignment of chiral drugs,especially for the oily or semisolid substances,whose crystal structures are impossible to obtain.     

Enzyme-catalysed synthesis and absolute configuration assignments of cis-dihydrodiol metabolites from 1,4-disubstituted benzenes

A series of ten cis-dihydrodiol metabolites has been obtained by bacterial biotransformation of the corresponding 1,4-disubstituted benzene substrates using Pseudomonas putida UV4, a source of toluene dioxygenase (TDO). Their enantiomeric excess (ee) values have been established using chiral stationary phase HPLC and 1H NMR spectroscopy. Absolute configurations of the majority of cis-dihydrodiols have been established using stereochemical correlation and X-ray crystallography and the remainder have been tentatively assigned using NMR spectroscopic methods but finally confirmed by circular dichroism (CD) spectroscopy. These configurational assignments support and extend the validity of an empirical model, previously used to predict the preferred stereochemistry of TDO-catalysed cis-dihydroxylation of ten 1,4-disubstituted benzene substrates, to more than twenty-five examples.     

Absolute Configuration Assignment from Optical Rotation Data by Means of Biphenyl Chiroptical Probes

A non-empirical approach for the assignment of the absolute configuration of chiral 2-alkyl-substituted carboxylic acids and primary amines by [α]_D measurements has been developed. The method requires the conversion of the chiral acids or amines into the corresponding 4,4′-disubstituted biphenylamides or biphenylazepines, respectively. In these derivatives a central-to-axial chirality transfer induces a preferred torsion in the biphenyl moiety revealed by the sign of the biphenyl A band in the ECD spectrum. By 4,4′-substitution on the biphenyl moiety a redshift of the A band is obtained, leading to an increase of its relative contribution to optical rotation. This allows to reliably establish a direct correlation between the [α]_D sign, the biphenyl twist and, then, the substrate absolute configuration. This approach thus constitutes a really practical and reliable method to assign the absolute configuration of chiral carboxylic acids and primary amines by simple and straightforward [α]_D measurement, readily obtainable by a routine instrumentation like the polarimeter.     

Temperature dependence of the optical rotation in six bicyclic organic molecules calculated by vibrational averaging.

The vibrational corrections and the temperature dependence of the specific rotation of six rigid organic molecules (alpha-pinene, beta-pinene, cis-pinane, camphene, camphor, and fenchone) were calculated at three wavelengths using hybrid time-dependent density functional theory (TDDFT). A technique for calculating the temperature dependence of the vibrational average of a molecular property has been applied to obtain the specific rotation of the molecules as a function of temperature. For cases in which accurate equilibrium optical rotations can be obtained as a "base value," and for which there is little effect from solvation, accurate predictions of the trends in the temperature-dependence of the specific rotations can be calculated. For other cases, the method can be used to extract purely vibrational contributions to the overall temperature dependence of optical rotation.     

Absolute configuration of bioactive furanogermacrenones from Commiphora erythraea (Ehrenb) Engl. by computational analysis of their chiroptical properties

Absolute configurations (+)-(4S), (+)-(3S,4R), (−)-(2S,4S), and (−)-(1R,2R,4S) were assigned, for the first time, to bioactive furanogermacranes extracted from Commiphora erythraea resin by DFT computational analysis of their ORD curves and ECD spectra. This analysis established that all of these compounds share the same absolute configuration at the methyl-substituted carbon thus allowing us to hypothesize a biosynthetic relationship among these structurally related metabolites.     

Toluene Dioxygenase‐Catalyzed Synthesis of cis‐Dihydrodiol Metabolites from 2‐Substituted Naphthalene Substrates: Assignments of Absolute Configurations and Conformations from Circular Dichroism and Optical Rotation Measurements

cis‐Dihydrodiol metabolites have been isolated from naphthalene and six 2‐substituted naphthalene substrates. Their structures and absolute configurations have been determined by a combination of calculated (TDDFT) and experimentally based circular dichroism (CD) and optical rotation (OR) methods. The “inverse” styrene helicity rule is shown to be incorrect for the interpretation of the CD spectra of cis‐dihydrodiols. A striking conclusion is that CD spectra correlate directly with the helicity of the styrene chromophore: that is, the sign of the long‐wavelength Cotton effect is identical with the sign of styrene torsion angle, whereas the OR sign is dependent on the absolute configuration of the allylic carbon atom. The results demonstrate that a predictive model previously used for the determination of preferred regio‐ and stereoselectivity associated with TDO‐catalyzed cis‐dihydroxylation of substituted benzene substrates can now be successfully extended to substituted naphthalene substrates.     

Determination of the Absolute Configuration of Perylene Quinone‐Derived Mycotoxins by Measurement and Calculation of Electronic Circular Dichroism Spectra and Specific Rotations

Altertoxins I–III, alterlosins I and II, alteichin (alterperylenol), stemphyltoxins I–IV, stemphyperylenol, stemphytriol, 7‐epi‐8‐hydroxyaltertoxin I, and 6‐epi‐stemphytriol are mycotoxins derived from perylene quinone, for which the absolute configuration was not known. Electronic circular dichroism (ECD) spectra were calculated for these compounds and compared with measured spectra of altertoxins I–III, alteichin, and stemphyltoxin III and with reported Cotton effects. Specific rotations were calculated and compared with reported specific rotations. The absolute configuration of all the toxins, except for stemphyltoxin IV, could thus be determined. The validity of the assignment was high whenever reported ECD data were available for comparison, and the validity was lower when the assignment was based only on the comparison of calculated and reported specific rotations. ECD spectra are intrinsically different for toxins with a biphenyl substructure and for toxins derived from dihydroanthracene.     

分子旋光度的密度泛函计算及Soman绝对构型确定

手性化合物绝对构型的确定一直是有机化学特别是手性药物合成研究过程中经常遇到的问题之一. 利用密度泛函DFT/B3LYP量子化学计算方法, 通过计算两种已知旋光度分子的旋光度, 确认计算条件和验证计算结果的可靠性, 并将此方法应用于Soman旋光度的计算. 结合文献报道的Soman分子实验旋光度测定结果, 首次采用理论计算方法确定了梭曼(Soman)分子四个异构体的绝对构型, 分别为P(R),C(S)-Soman→P(＋)C(＋), P(R),C(R)-Soman→P(＋)C(－), P(S),C(S)-Soman→P(－)C(＋), P(S),C(R)-Soman→P(－)C(－).     

Synthesis of Enantiopure Sulfonimidamides and Elucidation of Their Absolute Configuration by Comparison of Measured and Calculated CD Spectra and X‐Ray Crystal Structure Determination

Straightforward syntheses of enantiopure N‐benzoyl‐ and N‐tert‐butyloxycarbonyl‐protected sulfonimidamides, which can be used as building blocks in newly designed catalysts, are presented. Key synthetic step is a dynamic resolution of a racemic sulfinic acid sodium salt. All subsequent transformations proceed stereospecifically. The absolute configurations at the sulfur atoms of both sulfonimidamides were determined by comparison of measured and calculated CD spectra. An X‐ray crystal structure determination of a sulfonimidoylguanidine derivative confirmed this result.     

Absolute configuration of C2-symmetric spiroselenurane: 3,3,3',3'-tetramethyl-1,1'-spirobi[3 H,2,1]benzoxaselenole

The enantiomers of 3,3,3',3'-tetramethyl-1,1'-spirobi[3 H,2,1]benzoxaselenole have been separated on a chiral preparative chromatographic column. The experimental vibrational circular dichroism (VCD) spectra have been obtained for both enantiomers in CH(2)Cl(2). The theoretical VCD spectra have been obtained by means of density functional theoretical calculations with the B3 LYP density functional. From a comparison of experimental and theoretical VCD spectra, the absolute configuration of an enantiomer with positive specific rotation in CH(2)Cl(2) at 589 nm is determined to be R. This conclusion has been verified by comparing results of experimental optical rotatory dispersion (ORD) and electronic circular dichroism (ECD) to predictions of the same properties using the B3 LYP functional for the title compound.     

Origin‐independent sum over states simulations of magnetic and electronic circular dichroism spectra via the localized orbital/local origin method

Although electronic and magnetic circular dichroism (ECD, MCD) spectra reveal valuable details about molecular geometry and electronic structure, quantum‐chemical simulations significantly facilitate their interpretation. However, the simulated results may depend on the choice of coordinate origin. Previously (?těpánek and Bou?, J. Comput. Chem. 2013, 34, 1531), the sum‐over‐states (SOS) methodology was found useful for efficient MCD computations. Approximate wave functions were “resolved” using time‐dependent density functional theory, and the origin‐dependence was avoided by placing the origin to the center of mass of the investigated molecule. In this study, a more elegant way is proposed, based on the localized orbital/local origin (LORG) formalism, and a similar approach is also applied to generate ECD intensities. The LORG‐like approach yields fully origin‐independent ECD and MCD spectra. The results thus indicate that the computationally relatively cheap SOS simulations open a new way of modeling molecular properties, including those involving the origin‐dependent magnetic dipole moment operator. © 2015 Wiley Periodicals, Inc.     

Phenyl‐(2‐pyridyl)‐(3‐pyridyl)‐(4‐pyridyl)methane: Synthesis,Chiroptical Properties,and Theoretical Calculation of Its Absolute Configuration

The title compound, a prototypical chiral molecule based on a tetraarylmethane framework, has been synthesized in five steps from (2‐pyridyl)‐(3‐pyridyl)ketone. X‐ray crystallographic analysis revealed the tetraarylmethane framework of the molecule but did not determine the positions of the nitrogen atoms because the crystal is a racemic compound and the aryl groups are disordered in the crystal. The optical resolution of the title compound was achieved by chiral HPLC with a Chiralcel OD column. The CD spectra of the two fractions in acetonitrile exhibited opposite signs as expected for a pair of enantiomers. Their CD spectra are changed in 2 M HCl due to protonation. The calculated CD curve for the target molecule based on time‐dependent density functional theory (TDDFT) reproduces the experimental result very well, thus suggesting that the first eluted fraction is the R isomer in terms of absolute configuration.     

Time‐dependent density functional theory calculations on the chiroptical properties of rubroflavin: Determination of its absolute configuration by comparison of measured and calculated CD spectra

The absolute configuration of rubroflavin has been determined by comparison of its measured and calculated CD spectra. For this purpose the structures of 30 plausible isomers of the title compound have been optimized with density functional theory (DFT/BP86) using a triple‐zeta valence basis set. The absolute (S) configuration at the ? S(?O)CH₃ group has been assumed in these calculations. One quinoid isomer, which is separated from all other structures by an energy gap of about 4 kcal/mol, was found to be the most stable species and to dominate the CD spectrum. The structure of this isomer has been reoptimized under the influence of a solvent using an electrostatic model (COSMO). Based on the geometries of the most stable isomer obtained in the presence and absence of the solvent the excitation energies and oscillator as well as rotational strengths have then been calculated using time‐dependent DFT (TDDFT/TZVP/BP86). Comparison of the measured CD spectrum with that calculated for the energetically lowest isomer shows that especially the long wavelength parts of the spectra agree fairly well as far as the wavelengths and the signs of the Cotton effects are concerned while the correspondence between calculated and measured intensities is less satisfying. The agreement between the measured and calculated spectrum is better if the geometry optimized under the influence of the solvent is used. A detailed analysis of the spectra led us to the conclusion that the absolute configuration of rubroflavin is (S). These results support earlier assignments based on semiempirical and ab initio studies on a thermal decomposition product of rubroflavin. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 265–270, 2003     

Three Types of Induced Tryptophan Optical Activity Compared in Model Dipeptides: Theory and Experiment

The tryptophan (Trp) aromatic residue in chiral matrices often exhibits a large optical activity and thus provides valuable structural information. However, it can also obscure spectral contributions from other peptide parts. To better understand the induced chirality, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA) spectra of Trp‐containing cyclic dipeptides c‐(Trp‐X) (where X=Gly, Ala, Trp, Leu, nLeu, and Pro) are analyzed on the basis of experimental spectra and density functional theory (DFT) computations. The results provide valuable insight into the molecular conformational and spectroscopic behavior of Trp. Whereas the ECD is dominated by Trp π–π* transitions, VCD is dominated by the amide modes, well separated from minor Trp contributions. The ROA signal is the most complex. However, an ROA marker band at 1554 cm^?1 indicates the local χ₂ angle value in this residue, in accordance with previous theoretical predictions. The spectra and computations also indicate that the peptide ring is nonplanar, with a shallow potential so that the nonplanarity is primarily induced by the side chains. Dispersion‐corrected DFT calculations provide better results than plain DFT, but comparison with experiment suggests that they overestimate the stability of the folded conformers. Molecular dynamics simulations and NMR results also confirm a limited accuracy of the dispersion‐DFT model in nonaqueous solvents. Combination of chiral spectroscopies with theoretical analysis thus significantly enhances the information that can be obtained from the induced chirality of the Trp aromatic residue.     

Determination of molecular stereochemistry using vibrational circular dichroism spectroscopy: absolute configuration and solution conformation of 5-formyl-cis,cis-1,3,5-trimethyl-3-hydroxymethylcyclohexane-1-carboxylic acid lactone

The determination of the absolute configuration of chiral molecules is an important aspect of molecular stereochemistry. Vibrational circular dichroism (VCD) is the extension of electronic CD into the infrared region where fundamental vibrational transitions occur. VCD has a number of advantages over all previous methods of absolute configuration assignment. The absolute configuration and predominant solution-state conformation in CDCl(3) of the chiral lactone, 5-formyl-cis,cis-1,3,5-trimethyl-3-hydroxymethylcyclohexane-1-carboxylic acid lactone, 1, obtained by the comparison of measured and calculated VCD spectra, are reported. It is found that (-)-1 corresponds to the absolute configuration (1S,3S,5R)-1.     

Vibrational Circular Dichroism and Theoretical Study of the Conformational Equilibrium in (−)‐S‐Nicotine

We report an extensive study of the molecular and electronic structure of (?)‐S‐nicotine, to deduce the phenomenon that controls its conformational equilibrium and to solve its solution‐state conformer population. Density functional theory, ab initio, and molecular mechanics calculations were used together with vibrational circular dichroism (VCD) and Fourier transform infrared spectroscopies. Calculations and experiments in solution show that the structure and the conformational energy profile of (?)‐S‐nicotine are not strongly dependent on the medium, thus suggesting that the conformational equilibrium is dominated by hyperconjugative interactions rather than repulsive electronic effects. The analysis of the first recorded VCD spectra of (?)‐S‐nicotine confirmed the presence of two main conformers at room temperature. Our results provide further evidence of the hypersensitivity of vibrational optical activity spectroscopies to the three‐dimensional structure of chiral samples and prove their suitability for the elucidation of solution‐state conformer distribution.