首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
Chiroptical techniques are increasingly employed for assigning the absolute configuration of chiral molecules through comparison of experimental spectra with theoretical predictions. For assignment of natural products, electronic chiroptical spectroscopies such as electronic circular dichroism (ECD) are routinely applied. However, the sensitivity of electronic spectral parameters to experimental conditions and the theoretical methods employed can lead to incorrect assignments. Vibrational chiroptical methods (vibrational circular dichroism, VCD, and Raman optical activity, ROA) provide more reliable assignments, although they, in particular ROA, have been little explored for assignments of natural products. In this study, the ECD, VCD, and ROA chiroptical spectroscopies are evaluated for the assignment of the absolute configuration of a highly flexible natural compound with two stereocenters and an asymmetrically substituted double bond, the marine antibiotic Synoxazolidinone A (SynOxA), recently isolated from the sub-Arctic ascidian Synoicum pulmonaria. Conformationally averaged nuclear magnetic resonance (NMR), ECD, Raman, ROA, infrared (IR) and VCD spectral parameters are computed for the eight possible stereoisomers of SynOxA and compared to experimental results. In contrast to previously reported results, the stereochemical assignment of SynOxA based on ECD spectral bands is found to be unreliable. On the other hand, ROA spectra allow for a reliable determination of the configuration at the double bond and the ring stereocenter. However, ROA is not able to resolve the chlorine-substituted stereogenic center on the guanidinium side chain of SynOxA. Application of the third chiroptical method, VCD, indicates unique spectral features for all eight SynOxA isomers in the theoretical spectra. Although the experimental VCD is weak and restricted by the limited amount of sample, it allows for a tentative assignment of the elusive chlorine-substituted stereocenter. VCD chiroptical analysis of a SynOxA derivative with three stereocenters, SynOxC, results in the same absolute configuration as for SynOxA. Despite the experimental challenges, the results convincingly prove that the assignment of absolute configuration based on vibrational chiroptical methods is more reliable than for ECD.  相似文献   

2.
We present the determination of the conformational properties of aeroplysinin-1 in aqueous solution by means of a combined experimental and theoretical Raman optical activity (ROA) and vibrational circular dichroism (VCD) study. Aeroplysinin-1 is an antiangiogenic drug extracted from the sponge Aplysina cavernicola which has been proved to be a valuable candidate for the treatment of cancer and other antiangiogenic diseases. Our study shows that this molecule possesses the 1S,6R absolute configuration in aqueous solution, where only two conformers are present to a significant level. We discuss in detail the relationships between the chiro-optical ROA and VCD features, and the structural properties of various energy accessible conformers are described. The present work is one of the first studies in which both ROA and VCD have been used as complementary tools for the determination of absolute configuration and dominant solution-state conformations of an unknown therapeutically significant molecule.  相似文献   

3.
Determining the absolute stereochemistry of organic compounds in solution remains a challenge. We investigated the use of Raman optical activity (ROA) spectroscopy to address this problem. The absolute configurations of (+)-(R)- and (-)-(S)-limonene were determined by ROA spectroscopy, which can be applied to smaller amounts of sample as compared with vibrational circular dichroism (VCD) spectroscopy. This ROA method was also applied to (+)-(E)-alpha-santalol and shown to be successful in the determination of the absolute configuration of this compound. ROA spectroscopy shows promise as a useful tool for determining the absolute stereochemistry of many natural compounds.  相似文献   

4.
Vibrational circular dichroism (VCD) measurements and density functional theory (DFT) calculations were used to obtain the absolute configuration of optically pure cryptophane-A molecule. This large molecule (120 atoms) that possess a globular shape, but no chiral centers, exceeds the molecular size of published structures for which VCD has been used to determine the absolute configuration. VCD spectra recorded in CDCl(3) solution for the two resolved enantiomers are near mirror images, and very good agreement between the observed IR and VCD spectra and intensity calculations performed at the DFT (B3PW91/6-31G) level establish, besides the absolute configuration, the preferential anti conformation of the aliphatic linkers of the chloroform-cryptophane-A complex. Experiments performed in CD(2)Cl(2) and C(2)D(2)Cl(4) solutions show no significant modifications in the IR and VCD spectra, indicating that the conformation of the aliphatic linkers is similar for empty (C(2)D(2)Cl(4) solution) and encaged (CDCl(3) and CD(2)Cl(2) solutions) cryptophane-A molecules.  相似文献   

5.
The absolute configuration and conformation of 1-phenylethanol (1-PhEtOH) have been determined by matrix-isolation infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. Quantum chemical calculations have identified that there are three conformers, namely, I, II, and III, in which characteristic intramolecular interactions are found. The IR spectrum-conformation correlation for 1-PhEtOH has been developed by the Ar matrix-isolation IR measurement and used for the assignments of the observed IR bands. In a dilute CCl(4) solution, 1-PhEtOH exists predominantly as conformer I along with a trace amount of conformer II. By considering conformations and intermolecular hydrogen-bonding in the spectral simulation for (S)-1-PhEtOH, we have successfully reproduced the VCD spectrum of (-)-1-PhEtOH observed in a dilute CS(2) solution. Thus, (-)-1-PhEtOH is of S-configuration and conformer I in the dilute solution. The same method has been applied to analyze the VCD spectra measured in the liquid state of (-)-1-PhEtOH. The absolute configuration of 1-PhEtOH in the condensed phase is enabled by identifying VCD bands that are insensitive to conformational changes and intermolecular interactions. The present work provides a combinatorial procedure for determination of both the absolute configuration and the conformation of chiral molecules in a dilute solution and condensed phase.  相似文献   

6.
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.  相似文献   

7.
Absorption and vibrational circular dichroism (VCD) spectra of the title compound, a common intermediate in synthesis of many pharmaceuticals, were measured and analyzed in order to determine its absolute configuration and prevailing conformations. The analysis was combined with a systematic conformer search based on relative energies as well as with comparison of experimental and computed NMR shifts. The spectra were interpreted on the basis of ab initio simulations. The results indicate that the compound adopts exclusively a chair conformation of the piperidine ring with all the fluorophenyl, hydroxymethyl, and methyl substituents attached in equatorial positions. A limited rotation of the hydroxymethyl group is most consistent with the observed VCD pattern. VCD parameters were found significantly more sensitive to conformational changes than absorption or NMR. Concentration dependence of the absorption spectra indicated aggregation in concentrated solutions, but involved hydrogen bonds probably do not influence molecular conformation.  相似文献   

8.
A combined theoretical and experimental study of the vibrational absorption (VA)/IR, vibrational circular dichroism (VCD), Raman and Raman optical activity (ROA) spectra of l-histidine in aqueous solution has been undertaken to answer the questions (i) what are the species present and (ii) which conformers of the species are present under various experimental conditions. The VA spectra of l-histidine have been measured in aqueous solution and the spectral bands which can be used to identify both species (cation, zwitterion, anion) and conformer of the species have been identified and subsequently used to identify the species (zwitterion) and conformer (gauche minus minus, gauche minus plus for the side chain dihedral angles) present in solution at pH 7.6. The VCD spectral intensities have been used subsequently in combination with further theoretical studies to confirm the conclusions that have been arrived at by only analyzing the VA/IR spectra. Finally a comparison of measured Raman and ROA spectra of l-histidine with Raman and ROA spectral simulations for the conformers and species derived from the combined VA/IR and VCD experimental and theoretical work is presented as a validation of the conclusions arrived at from VA/IR and VCD spectroscopy. The combination of VA/IR and VCD with Raman and ROA is clearly superior and both sets of experiments should be performed.  相似文献   

9.
In this work we present the experimental and theoretical vibrational absorption (VA) and the theoretical vibrational circular dichroism (VCD) spectra for aframodial. In addition, we present the theoretical VA and VCD spectra for the diasteriomers of aframodial. Aframodial has four chiral centers and hence has 24 = 16 diasteriomers, which occur in eight pairs of enantiomers. In addition to the four chiral centers, there is an additional chirality due to the helicity of the entire molecule, which we show by presenting 12 configurations of the 5S,8S,9R,10S enantiomer of aframodial. The VCD spectra for the diasteriomers and the 12 configurations of one enantiomer are shown to be very sensitive not only to the local stereochemistry at each chiral center, but in addition, to the helicity of the entire molecule. Here one must be careful in analyzing the signs of the VCD bands due to the ‘non-chiral’ chromophores in the molecule, since one has two contributions; one due to the inherent chirality at the four chiral centers, and one due to the chirality of the side chain groups in specific conformers, that is, its helicity. Theoretical simulations for various levels of theory are compared to the experimental VA recorded to date. The VCD spectra simulations are presented, but no experimental VCD and Raman spectra have been reported to date, though some preliminary VCD measurements have been made in Stephens’ lab in Los Angeles. The flexible side chain is proposed to be responsible for the small size of the VCD spectra of this molecule, even though the chiral part of the molecule is very rigid and has four chiral centers. In addition to VCD and Raman measurements, Raman optical activity (ROA) measurements would be very enlightening, as in many cases bands which are weak in both the VA and VCD, may be large in the Raman and/or ROA spectra. The feasibility of using vibrational spectroscopy to monitor biological structure, function and activity is a worthy goal, but this work shows that a careful theoretical analysis is also required, if one is to fully utilize and understand the experimental results. The reliability, reproduceability and uniqueness of the vibrational spectroscopic experiments and the information which can be gained from them is discussed, as well as the details of the computation of VA, VCD and Raman (and ROA) spectroscopy for molecules of the complexity of aframodial, which have multiple chiral centers and flexible side chains. Festschrift in Honor of Philip J. Stephens’ 65th Birthday.  相似文献   

10.
The determination of absolute configurations of chiral compounds using VCD is performed by comparing measured vibrational circular dichroism (VCD) spectra with calculated spectra. The process is based on two facts: the two enantiomers have rotational strengths of opposite sign, and the absolute configuration of the molecule used in the calculation is known. However, calculations on isolated molecules very often predict VCD intensities of very different magnitude or even different signs compared to the spectra measured in solution. Therefore, we have carefully analyzed what type of changes are induced by complexation of a solvent molecule to a solute. In the theoretical example of benzoyl-benzoic acid (in a particular chiral conformation) hydrogen bonded to the achiral NH3, we distinguish six cases, ranging from no or very small changes in the rotational strengths of solute modes (case A) to changes of sign of rotational strengths (case B), changes in magnitude (case C), nonzero rotational strengths for modes of the achiral solvent ("transfer of chirality", case D), large frequency shifts accompanied by giant enhancements of the IR and VCD intensities of modes involved in hydrogen bonding (case E), and emergence of new peaks (case F). In this work, all of these situations will be discussed and their origin will be elucidated. On the basis of our analysis, we advocate that codes for VCD rotational strength calculation should output for each mode i the angle xi(i) between the electric and magnetic transition dipole moments because only "robust modes" with xi far from 90 degrees should be used for the determination of the absolute configuration.  相似文献   

11.
The enantiomers of tert-butyl(dimethylamino)phenylphosphine-borane complex 2 have been separated by HPLC using cellulose tris-p-methylbenzoate as chiral stationary phase. The borane protection could be removed without racemization and the P-configuration of the free aminophosphine 1 has shown to be stable in solution. Infrared (IR) and vibrational circular dichroism (VCD) spectra have been measured in CD2Cl2 solution for both enantiomers. B3LYP/6-31+G(d) DFT calculations allowed a prediction that complex (S)-2 exists as three conformers in equilibrium and computed population-weighted IR and VCD spectra. Predicted and experimental IR and VCD spectra compared very well and indicate that enantiomer (+)-2 has the S absolute configuration. This assignment has been confirmed by an X-ray diffraction study on a single crystal of (+)-2. The crystal structure of enantiomerically pure 2 appears to be very close to the most stable computed conformer which proved to be predominant in solution.  相似文献   

12.
振动圆二色谱: 一种确定手性分子绝对构型的新方法   总被引:2,自引:0,他引:2  
甘礼社  周长新 《有机化学》2009,29(6):848-857
手性分子绝对构型的确定是一个极其重要且长期存在的问题. 振动圆二色谱是在红外波长区域测定分子圆二色性的一种新方法, 极大地扩展了圆二色谱的应用范围. 振动圆二色谱法通过构象搜索、量子化学计算等手段准确预测手性分子的振动圆二色谱图, 进而与实测谱图进行比较确定其绝对构型. 该方法已经得到了越来越广泛的应用, 必将成为一种有效测定手性分子绝对构型的常规方法.  相似文献   

13.
Mid-infrared vibrational unpolarised absorption and vibrational circular dichroism (VCD) spectra of CCl4 solutions of tert-butyl methyl sulfoxide (1) are reported. The spectra are compared to ab initio density functional theory (DFT) calculations carried out using two functionals, B3PW91 and B3LYP, and two basis sets, 6-31G* and TZ2P. The VCD spectra are calculated using Gauge-invariant atomic orbitals (GIAOs). The analysis of the VCD spectrum confirms the R(-)/S(+) absolute configuration of 1. The advantages and disadvantages of VCD spectroscopy in determining the absolute configurations of chiral sulfoxides are discussed.  相似文献   

14.
The reliable computation of Raman‐optical‐activity (ROA) spectra of molecules of the size of the title compounds has, until now, not been possible. We show that our rarefied basis sets yield results in good agreement with the experimental data for (4S)‐4‐methylisochromane (=(4S)‐3,4‐dihydro‐4‐methyl‐1H‐2‐benzopyran; 1 ), provided the equilibrium between the pseudo‐equatorial and the pseudo‐axial conformers is taken into account. Comparison between the measured and the computed ROA back‐scattering spectra allows the unequivocal assignment of the absolute configuration of the molecule. Comparison with more‐approximate calculations for the larger (4S)‐isomers of Galaxolide® ( 2 ), which contain the (4S)‐4‐methylisochromane moiety, shows large‐scale group frequencies on the same chiral fragments of the two molecules. The data confirm that ROA can be generated by interactions extending over several bonds, i.e., over larger distances than can be probed by NMR spectroscopy. Thus, the absolute configuration at C(7) of Galaxolide® is assignable independently of that at C(4). The computation of ROA for forward‐scattering, which will soon be measurable for Galaxolide®, suggests that this scattering geometry provides additional stereochemical information that will be valuable in situations where absolute configurations at several stereogenic centers have to be assigned.  相似文献   

15.
Vibrational absorption (IR) and circular dichroism (VCD) measurements of trans-(3S,4S)-d6-cyclopentene in the gas phase were performed in the C-H, C-D, and mid-infrared regions. In this study, we report the first VCD spectra recorded at high spectral resolution (up to 0.5 cm(-1)) with a very good signal-to-noise ratio (differential absorbance lower than 5 x 10(-6)). The quality of the experimental spectra allows us the observation of the vibration-rotation structure of the bands in both absorption and VCD spectra. Experimental spectra have been compared with the density functional theory (DFT) absorption and VCD spectra, calculated using B3LYP functional and cc-pVTZ basis set for the axial, equatorial, and planar conformers. Lorentzian and PQR band profiles have been used to convert the calculated dipolar and rotational strengths. In the mid-infrared (<2000 cm(-1)) region, predicted (population-weighted) spectra were in excellent agreement with experiment, allowing the determination of the absolute configuration of this molecule. Above 2000 cm(-1), a reasonable agreement was obtained even if anharmonicity was not considered and if Fermi resonance occurs in the C-D stretching region. Finally, a more precise analysis of the absorption spectrum has been achieved by taking into account anharmonicity of the C-H stretching and its coupling with the ring-puckering motion.  相似文献   

16.
New enantiopure cryptophanes 3-7 having C(1)-symmetry have been synthesized. Electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) have been used to investigate their chiroptical properties, and the results are compared to those obtained for cryptophane-A (1) having D(3)-symmetry. The ECD spectra of compounds 3-7 show Cotton effects that differ from those of cryptophane-A. However, our results suggest that a confident determination of the absolute configuration of the monofunctionalized cryptophanes can be made using ECD spectroscopy. Interestingly, we have found that the ECD spectra of cryptophanes, especially the (1)L(b) transition, are very sensitive to the nature of the solvent. These spectral modifications are essentially due to bulk solvent properties rather than the ability of a particular solvent to insert into the cavity of cryptophanes. On the other hand, VCD spectra of the monofunctionalized cryptophanes have not revealed significant spectral modifications with respect to the VCD spectrum of the CHCl(3) at cryptophane-A complex, except for CHCl(3) at 7 and to a smaller extent for CHCl(3) at 6. These spectral modifications, which essentially consist in lower intensities of VCD bands associated with the cryptophane backbone, were perfectly reproduced by ab initio calculations performed at DFT (B3PW91/6-31G*) level. These results clearly demonstrate that VCD measurements associated with DFT calculations allow an easy determination of the absolute configuration of cryptophane-A derivatives.  相似文献   

17.
Recently, it was observed that infrared (IR) and vibrational circular dichroism (VCD) calculations including deuterated hydroxyl groups in phenolic and saccharide moieties improved significantly the agreement with experimental data obtained in methanol-d4. In the present study, the relative and absolute configurations of three methanol-soluble caffeic acid ester derivatives 13, isolated from Tithonia diversifolia, were established by a combined use of experimental and calculated 13C NMR chemical shifts, as well as electronic circular dichroism (ECD) and VCD spectroscopies. Interestingly, the attempt to reproduce the deuteration pattern arising from possible isotopic exchange in methanol-d4 solution led to nearly mirror image calculated VCD spectra for 1 when compared to the non-deuterated molecule with the same absolute configuration. This latter fact can potentially lead to absolute configuration misassignments. A closer inspection of the vibrational chiroptical properties of 1 revealed that the deuteration status of the tertiary hydroxyl group at C-2 is critical for the correct reproduction of experimental VCD data in protic solvents. Therefore, in the case of stereochemical analysis of polar chiral natural product molecules, a combination of VCD and ECD is recommended.  相似文献   

18.
A vibrational Raman optical activity (ROA) study of a series of alanine peptides in aqueous solution is presented. The seven-alanine peptide Acetyl-OOAAAAAAAOO-Amide (OAO), recently shown by NMR and UVCD to adopt a predominantly poly(l-proline II) (PPII) helical conformation in aqueous solution, gave an ROA spectrum very similar to that of disordered poly(l-glutamic acid) which has long been considered to adopt the PPII conformation, both being dominated by a strong positive extended amide III ROA band at approximately 1319 cm-1 together with weak positive amide I ROA intensity at approximately 1675 cm-1. A series of alanine peptides Ala2-Ala6 studied in their cationic states in aqueous solution at low pH displayed ROA spectra which steadily evolved toward that of OAO with increasing chain length. As well as confirming that alanine peptides can support the PPII conformation in aqueous solution, our results also confirm the previous ROA band assignments for PPII structure, thereby reinforcing the foundation for ongoing ROA studies of unfolded and partially folded proteins.  相似文献   

19.
The absolute configuration of jatropholone A 1 and B 2, including the possibility to observe the vibrational circular dichroism (VCD) capacity to differentiate between two epimeric compounds in the presence of an inherently dissymmetric chromophore, which normally dominates VCD and electronic circular dichroism (ECD) spectra, followed after comparison of their experimental and DFT calculated VCD spectra, allowed us to conclude that although non-local (M/P) chirality generated by atropisomerism dominates over local chirality generated by an (R/S) change, the stereogenic center can confidently be assigned by VCD after DFT calculations. In addition, the absolute configurations of jatrophatrione 3 and citlalitrione 4, a compound proposed as a taxonomic marker for the genus Jatropha, were assigned by contrasting their respective calculated and experimental IR and VCD spectra. The evaluation of Flack and Hooft parameters obtained from the single-crystal X-ray diffraction data of jatropholone B acetate 6, and of 4 independently confirmed the absolute configurations of these molecules.  相似文献   

20.
Jacob CR 《Chemphyschem》2011,12(17):3291-3306
Raman optical activity (ROA) spectroscopy is a promising analytical method for studying the structure and conformation of polypeptides and proteins in solution. However, the structural information obtained from such vibrational spectra is only indirect and theoretical studies are often necessary to identify how the structure determines the observed spectra. One particular target is the identification and discrimination of different helical secondary structure elements. Herein, a theoretical investigation of the ROA spectra of a series of 3(10)-helical polypeptides is presented. In particular, the effect of chain length, C(α)-substitution pattern, the introduction of larger aliphatic side chains, and the variation of their conformation on the ROA spectra is studied. To extract general principles from these calculations, the positions, intensities, and shapes of the ROA bands are analyzed in terms of localized modes, which makes it possible to identify possible ROA signatures of 3(10) -helical structures, but also provides fundamental insight into the generation of ROA signals in complex polypeptides. Finally, the calculated spectra can be compared to the previously reported ROA spectrum of a specifically designed 3(10) -helical heptapeptide. This allows most of the features in the experimental spectrum to be assigned.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号