Determination of the Absolute Configuration of Rohitukine

The absolute configuration of rohitukine, isolated from the stem-bark of Dysoxylum binectariferum, was determined to be 5,7-dihydroxy-2-methyl-8-[4-(3S, 4R-3-hydroxy-1-methyl)-piperidinyl]-4H-l-benzopyran-4-one by X-ray crystallographic analysis on the crystal of,4-bromobenzoyl derivatives of rohitukine. At the same time, the modified Mosher method was proved to be unsuitable for determining the absolute configuration of C-3‘ position in rohitukine.     

Scobidiynediol的合成及绝对构型

本文报道了以光学活性乳酸为手性元对目标化合物的所有可能的四个异构体所进行的合成。根据合成样品与天然产物的核磁及旋光数据比较，标题化合物的相对及绝对构型都得以完全确立，其完整结构定为(2S,3S)-4,6-庚二炔-2,3-二醇。     

Absolute Configuration of Small Molecules by Co-Crystallization

The most reliable method to determine the absolute configuration of chiral molecules is X-ray crystallography, but small molecules can be difficult to crystallize. We report rapid co-crystallization of tetraaryladamantanes with small molecules as different as n-decane to nicotine to produce crystals for X-ray analysis and the assignment of absolute configuration when the molecules are chiral. A screen of 52 diverse compounds gave inclusion in co-crystals for 88 % of all cases and a high-resolution structure in 77 % of cases. Furthermore, starting from three milligrams of analyte, a combination of NMR spectroscopy and X-ray crystallography produced a full structure in less than three days using an adamantane crystallization chaperone that encapsulates the analyte at room temperature.     

Synthesis, Crystal Structure and AbsoluteConfiguration of （＋）-O-Phenyl Cyclophosphorodiamidate

The title compound, ( )-O-phenyl cyclophosphorodiamidate (C28H33N202P, Mr=460.53), has been synthesized and characterized by 31p NMR, 1H NMR and elemental analysis. X-ray diffraction analysis at 273(2) K indicates that it belongs to orthorhombic system, space group P212121 with a=11.518(4), b=13.449(4), c=16.539(5)A, V=2562(1)A3, Z=4, Dc=1.194g/cm3, F(000)=984 and μ(MoKα)=0.134mm-l. The structure parameters were refined by full-matrix least-squares on F2 to R=0.0459 and wR=0.0640. The flack χ parameter is 0.03(10), and the absolute configuration of the phosphorus atom in the title compound is S.     

Absolute Configuration of Small Molecules by Co‐Crystallization

The most reliable method to determine the absolute configuration of chiral molecules is X‐ray crystallography, but small molecules can be difficult to crystallize. We report rapid co‐crystallization of tetraaryladamantanes with small molecules as different as n‐decane to nicotine to produce crystals for X‐ray analysis and the assignment of absolute configuration when the molecules are chiral. A screen of 52 diverse compounds gave inclusion in co‐crystals for 88 % of all cases and a high‐resolution structure in 77 % of cases. Furthermore, starting from three milligrams of analyte, a combination of NMR spectroscopy and X‐ray crystallography produced a full structure in less than three days using an adamantane crystallization chaperone that encapsulates the analyte at room temperature.     

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.     

振动圆二色谱: 一种确定手性分子绝对构型的新方法

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.     

手性溶解剂在NMR法测定对映体比率和绝对构型的研究进展

综述了手性溶解剂在NMR法测定对映体比率及绝对构型的研究进展.按照手性溶解剂的结构类型,包括胺、酰胺、羧酸、醇、氨基醇、大环化合物,对手性溶解剂的结构特点与手性识别性能进行了详细的介绍.     

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(－).     

Determination of the Absolute Configuration of the Pseudo‐Symmetric Natural Product Elatenyne by the Crystalline Sponge Method

Elatenyne is a marine natural product that was isolated in 1986. Despite its simple 2,2′‐bifuranyl backbone, its relative structure was only recently determined. The absolute configuration of elatenyne has still not been unequivocally confirmed because of its pseudo‐meso core structure, which results in a specific rotation, [α]_D , of almost zero. In this work, the structure of natural elatenyne was determined by the crystalline sponge method and the use of a porous coordination network (a crystalline sponge) capable of absorbing organic guests; in the sponge, the absorbed guests are ordered and crystallographically observable. The crystalline sponge could differentiate between the two very similar alkyl side chains, and the absolute structure of elatenyne was thus reliably determined. The total amount required for the experiments was only approximately 100 μg, and the majority (95 μg) could be recovered after the experiments.     

Synthesis,Crystal Structure and Absolute Configuration of (+)-(a-Hydroxybenzyl)phenylphosphinic acid

1 INTRODUCTION a-Hydroxyphosphonic acids and their esters are known to possess broad-based physiological activities and there is close links between biological efficacy and stereochemistry[1~3]. Optical active a-hydroxyphosphonic esters can also serve as useful precursors in organic synthesis[4, 5]. Here we will report the synthesis of optical active a-hydroxyphosphinic acid, (+)-(a-hydroxybenzyl)- phenylphosphinic acid and its crystal structure and the absolute configuration of its a-ca…     

Configurationally Stable Chiral Dithia‐Bridged Hetero[4]helicene Radical Cation: Electronic Structure and Absolute Configuration

A stable chiral hetero[4]helicene radical cation was synthesized and characterized by UV/Vis absorption and EPR spectroscopy, as well as X‐ray crystallography. For the first time, a combination of chiroptical methods involving ECD, ORD, and VCD, supported by quantum mechanical predictions, enabled the elucidation of the absolute configuration of such open‐shell helical species.     

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.     

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.     

Synthesis, Crystal Structure and Absolute Configuration of (+)-(а-Hydroxybenzyl)phenylphosphinic acid

The title compound (+)-((-hydroxybenzyl)phenylphosphinic acid (C13H13O3P, Mr = 248.20) has been synthesized and characterized by 31P NMR, 1H NMR and elemental analysis. X-ray diffraction analysis at 293(2) K indicates that the compound belongs to monoclinic system, space group C2 with cell parameters: a = 23.560(8), b = 6.947(2), c = 7.854(3) (A。）, β = 91.273(6)°, V = 1285.2(7) (A。）3, Z = 4, Dc = 1.283 g/cm3, F(000) = 520 and ((MoK() = 0.207 mm-1. The number of independent reflections amounts to 1991, of which 1507 are observed reflections. The crystal structure has been determined by direct methods (SHELXL-97). The structure parameters are refined by full-matrix least-squares on F2 to R = 0.0437 and wR = 0.0893. The flack x parameter is - 0.0001. The absolute configuration of the (-carbon in the title compound is S.     

Absolute Configuration from Different Multifragmentation Pathways in Light‐Induced Coulomb Explosion Imaging

The absolute configuration of individual small molecules in the gas phase can be determined directly by light‐induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X‐ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break‐up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light‐induced CEI.     

Determination of the Absolute Configuration of Pentacoordinate Chiral Phosphorus Compounds in Solution by Using Vibrational Circular Dichroism Spectroscopy and Density Functional Theory

Vibrational circular dichroism (VCD) spectroscopic measurements and density functional theory (DFT) calculations have been used to obtain the absolute structural information about four sets of diastereomers of pentacoordinate spirophosphoranes derived separately from l‐ (or d‐ ) valine and l‐ (or d‐ ) leucine for the first time. Each compound contains three stereogenic centers: one at the phosphorus center and two at the amino acid ligands. Extensive conformational searches for the compounds have been carried out and their vibrational absorption (VA) and VCD spectra have been simulated at the B3LYP/6‐311++G** level. Although both VA and VCD spectra are highly sensitive to the structural variation of the apical axis, that is, the O? P? O or N? P? O arrangement, the rotamers generated by the aliphatic amino side chains show little effect on both. The dominant experimental VCD features in the 1100–1500 cm^?1 region were found to be controlled by the chirality at the phosphorus center, whereas those at the C?O stretching region are determined by the chirality of the amino acid ligands. The good agreement between the experimental VA and VCD spectra in CDCl₃ solution and the simulated ones allows us to assign the absolute configurations of these pentacoordinate phosphorus compounds with high confidence. This study shows that the VCD spectroscopy complemented with DFT calculations is a powerful and reliable method for determining the absolute configurations and dominating conformers of synthetic phosphorus coordination complexes in solution.     

Synthesis,Chiral Resolution and Enantiomers Absolute Configuration of 4-Nitropropranolol and 7-Nitropropranolol

We recently identified 6-nitrodopamine and other nitro-catecholamines (6-nitrodopa, 6-nitroadrenaline), indicating that the endothelium has the ability to nitrate the classical catecholamines (dopamine, noradrenaline, and adrenaline). In order to investigate whether drugs could be subject to the same nitration process, we synthesized 4-nitro- and 7-nitropropranolol as probes to evaluate the possible nitration of the propranolol by the endothelium. The separation of the enantiomers in very high yields and excellent enantiopurity was achieved by chiral HPLC. Finally, we used Riguera’s method to determine the absolute configuration of the enantiomers, through double derivatization with MPA and NMR studies.