Synthesis and sensory evaluation of all stereoisomers of sedanolide

Synthesis and sensory evaluation of all stereoisomers of sedanolide (1) are described. The asymmetric synthesis was achieved with using the all stereoisomers of bromoalcohol (3) prepared by enzymatic resolution and inversion of the secondary alcohol. All four stereoisomers of 1 were obtained in high enantiomeric purities (>99% ee). Their sensory evaluation revealed that there were distinct differences among the stereoisomers.     

Linalool and lilac aldehyde/alcohol in flower scents. Electrophysiological detection of lilac aldehyde stereoisomers by a moth

The stereoisomers of linalool and lilac aldehyde/alcohol were determined in the flower scent of 15 plant species using enantioselective multidimensional gas chromatography/mass spectrometry (enantio-MDGC/MS). Both linalool and all 8 stereoisomers of lilac alcohol and lilac aldehyde were detected, and there was a species-specific pattern. Single stereoisomers were collected by micropreparative-enantio-MDGC and were electrophysiologically tested on antennae of the noctuid moth Hadena bicruris, a species known to rely on lilac aldehyde for finding its host plant. The moth responded to all 8 stereoisomers, though only four stereoisomers were found in the scent of its host plant. The moth was less sensitive to some isomers than to others.     

环斑铂立体异构体与DNA的作用

研究了环斑铂的三种立体异构体（RSRR和SS）与小牛胸腺DNA的作用．用等温滴定量热法（ITC）测得三种化合物与DNA在298．15K时相互作用的摩尔烙变分别为-1．1,－7．2和16KJ·mol－1;差示扫描量热法（DSC）结果证实三种化合物与DNA作用使得其解链温度分别升高3．56,7.66和8．53K;而圆二色性波谱研究（CD）则显示出在室温时三种化合物与DNA间的作用使得其摩尔椭圆度发生了不等的微弱变化;核磁共振波谱法（NMR）结果告诉我们在室温时DNA的加入未使SS-环斑铂1H谱的化学位移及峰型出现明显的改变．综合热力学及波谱实验结果,对环斑钥立体异构体与DNA作用及结合的方式进行了讨论．     

Note on the application of low voltage mass spectrometry to stereochemical problems

Using the stereoisomeric 1,2-dimethyl-4-alkyldecahydroquinol-4-ols and various examples described elsewhere it was shown that there are many cases when decreasing of the electron energy does not lead to an increase in the quantitative differences between the mass spectra of stereoisomers.     

Gas chromatographic separation of the stereoisomers of organophosphorus chemical warfare agents using cyclodextrin capillary columns

The synthesis of the organophosphorus nerve agents sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) produces a mixture of two stereoisomers except for soman where four stereoisomers are produced. Significant differences exist in the reported toxicity and AChE inhibition rates of the various stereoisomers. This makes the ability to distinguish between the different stereoisomers desirable. Five different derivatized cyclodextrin stationary phases developed for gas chromatography were tested for their ability to resolve the nerve agent stereoisomers using a gas chromatograph interfaced to an atomic emission detector. Of the five columns that we examined, only the 2,6-di-O-pentyl-3-O-trifluoroacetyl or 2,6-di-O-pentyl-3-O-butyryl γ-cyclodextrins were able to successfully resolve all four soman stereoisomers. The elution order for each column was determined using solutions of isolated soman stereoisomers. Enantiomers of sarin, tabun, and GF were resolved with varying degrees of success on the different cyclodextrin stationary phases. Only the butyryl γ-cyclodextrin was able to separate the enantiomers of all four of the nerve agents examined in this study. The capacity (k) and selectivity (α) factors were determined for each of the chemical warfare agents successfully separated. The TNO Prins Maurits Laboratory in the Netherlands has previously developed several different chromatographic methods to resolve the stereoisomers of soman, sarin, and tabun. The advantage of the method described here is that commercially available cyclodextrin gas chromatography columns were used to resolve the stereoisomers, thereby facilitating rapid and routine analysis of organophosphorus nerve agents.     

Efficient enumeration of stereoisomers of tree structured molecules using dynamic programming

Nonredundant and exhaustive generation of stereoisomers of a chemical compound with a specified constitution is one of the important tools for molecular structure elucidation and molecular design. In this paper, we deal with chemical compounds composed of carbon, hydrogen, oxygen and nitrogen atoms whose graphical structures are tree-like graphs because these compounds are most fundamental, and consider stereoisomers that can be generated by asymmetric carbon atoms and double bonds between two adjacent carbon atoms. Based on dynamic programming, we propose an algorithm of generating all stereoisomers without duplication. We treat a given tree-like graph as a tree rooted at its structural center. Our algorithm first computes recursively the numbers of stereoisomers of the subgraphs induced by the descendants of each vertex, and then constructs each stereoisomer by backtracking the process of computing the numbers of stereoisomers. Our algorithm correctly counts the number of stereoisomers in O(n) time and space, and correctly enumerates all the stereoisomers in O(n) space and in O(n) time per stereoisomer, where n is the number of atoms in a given structure. The source code of the program implementing the proposed algorithm is freely available for academic use upon request.     

Efficient enumeration of stereoisomers of outerplanar chemical graphs using dynamic programming

Exhaustive and nonredundant generation of stereoisomers of a chemical compound with a specified constitution is an important tool for molecular structure elucidation and molecular design. It is known that many chemical compounds have outerplanar graph structures. In this paper we deal with chemical compounds composed of carbon, hydrogen, oxygen, and nitrogen atoms whose graphical structures are outerplanar and consider stereoisomers caused only by asymmetry around carbon atoms. Based on dynamic programming, we propose an algorithm of generating all stereoisomers without duplication. We treat a given outerplanar graph as a graph rooted at its structural center. Our algorithm first recursively computes the number of stereoisomers of the subgraph induced by the descendants of each vertex and then constructs each stereoisomer by backtracking the process of computing the numbers of stereoisomers. Our algorithm correctly counts the number of stereoisomers in O(n) time and space and correctly enumerates all of the stereoisomers in O(n3) time per stereoisomer on average and in O(n) space, where n is the number of atoms in a given structure.     

A Cheminformatics Study Regarding the Human Health Risks Assessment of the Stereoisomers of Difenoconazole

Difenoconazole is a chemical entity containing two chiral centers and having four stereoisomers: (2R,4R)-, (2R,4S)-, (2S,4R)- and (2S,4S)-difenoconazole, the marketed product containing a mixture of these isomers. Residues of difenoconazole have been identified in many agricultural products and drinking water. A computational approach has been used to evaluate the toxicological effects of the difenoconazole stereoisomers on humans. It integrates predictions of absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles, prediction of metabolism sites, and assessment of the interactions of the difenoconazole stereoisomers with human cytochromes, nuclear receptors and plasma proteins by molecular docking. Several toxicological effects have been identified for all the difenoconazole stereoisomers: high plasma protein binding, inhibition of cytochromes, possible hepatotoxicity, neurotoxicity, mutagenicity, skin sensitization potential, moderate potential to produce endocrine disrupting effects. There were small differences in the predicted probabilities of producing various biological effects between the distinct stereoisomers of difenoconazole. Furthermore, there were significant differences between the interacting energies of the difenoconazole stereoisomers with plasma proteins and human cytochromes, the spectra of the hydrogen bonds and aromatic donor–acceptor interactions being quite distinct. Some distinguishing results have been obtained for the (2S,4S)-difenoconazole: it registered the highest value for clearance, exposed reasonable probabilities to produce cardiotoxicity and carcinogenicity and negatively affected numerous nuclear receptors.     

用毛细管色谱法分析14种拟除虫菊酯立体异构体

用石英毛细管柱分离了14种拟菊酯的立体异构体。柱1用QF-1固定液10m×0.53mm×1.0μm膜厚,柱温在180℃～260℃之间,可完全分离右旋丙炔菊酯等10种拟菊酯的立体异构体。往2为HP-525m×0.53mm×1.0μm膜厚,用合适的住温可分离百治菊酯等4种拟菊酯的异构体。     

Analytical and semipreparative chiral separation of cis‐itraconazole on cellulose stationary phases by high‐performance liquid chromatography

cis‐Itraconazole is a chiral antifungal drug administered as a racemate. The knowledge of properties of individual cis‐itraconazole stereoisomers is vital information for medicine and biosciences as different stereoisomers of cis‐itraconazole may possess different affinity to certain biological pathways in the human body. For this purpose, either chiral synthesis of enantiomers or chiral separation of racemate can be used. This paper presents a two‐step high‐performance liquid chromatography approach for the semipreparative isolation of four stereoisomers (two enantiomeric pairs) of itraconazole using polysaccharide stationary phases and volatile organic mobile phases without additives in isocratic mode. The approach used involves the separation of the racemate into three fractions (i.e. two pure stereoisomers and one mixed fraction containing the remaining two stereoisomers) in the first run and consequent separation of the collected mixed fraction in the second one. For this purpose, combination of cellulose tris‐(4‐methylbenzoate) and cellulose tris‐(3,5‐dimehylphenylcarbamate) columns with complementary selectivity for cis‐itraconazole provided full separation of all four stereoisomers (with purity of each isomer > 97%). The stereoisomers were collected, their optical rotation determined and their identity confirmed based on the results of a previously published study. Pure separated stereoisomers are subjected to further biological studies.     

Estimation of the pH-independent binding constants of alanylphenylalanine and leucylphenylalanine stereoisomers with beta-cyclodextrin in the presence of urea

The separation of stereoisomers, particularly enantiomers, is important when their physiological activity differs. We have resolved the four stereoisomers each of alanylphenylalanine (Ala-Phe) and of leucylphenylalanine (Leu-Phe) by capillary electrophoresis using beta-cyclodextrin as a buffer additive and urea to enhance its solubility. A study of the influence of pH and beta-cyclodextrin concentration on the separations showed that weak inclusion complexes were formed between the dipeptides and chiral selector. It was found that pH could alter the migration order of enantiomers L-Ala-L-Phe and D-Ala-D-Phe, as well as L-Leu-L-Phe and D-Leu-D-Phe; however, there was no change in order for the other pairs of optical isomers. Electrophoretic mobility data were used to estimate the acid dissociation constants of the dipeptide isomers at pH < 7 with no chiral selector present. By varying the concentration of beta-cyclodextrin, the chiral selector, the binding constants of Ala-Phe and Leu-Phe optical isomers in their fully protonated and zwitterionic forms were estimated. For the four Ala-Phe stereoisomers, K = 42-66 M(-1) and 4-41 M(-1) for the cationic and zwitterionic forms, respectively. For the four Leu-Phe stereoisomers, K = 43-94 M(-1) and 1-28 M(-1) for the cationic and zwitterionic forms, respectively.     

Manual construction and mathematics- and computer-aided counting of stereoisomers. The example of oligoinositols

Two methods to obtain numbers of stereoisomers and of achiral stereoisomers of a given molecular structure are detailed on the example of di- and triinositols. The first method is manual exhaustive construction free of redundance of all stereoisomers, which is rendered feasible by symmetry considerations despite the large number of isomeric triinositols (82176). The second method is counting without constructing, made possible by use of a mathematical tool, the Cauchy-Frobenius lemma, which actually is a formalized manner of considering symmetry. The results are compared to those obtained by computer-aided stereoisomer generation using the program MOLGEN 3.5. It is demonstrated that in their results all three methods agree.     

High-performance liquid chromatographic analysis of the (cyanoaquo) stereoisomers of several putative vitamin B12 precursors

The cyanoaquo and aquocyano stereoisomers of several putative vitamin B12 precursors are reversibly formed and can be separated using analytical high-performance liquid chromatographic methods. The behavior of these stereoisomers varies somewhat depending on the type of column used and the chromatographic conditions employed. Both reversed-phase and ion-exchange columns can be used to observe the reversible formation and separation of the stereoisomers of (H2O,CN)cobyric acid, cobinamide and the cobinic acid pentaamide-1, -2 and -3 structural isomers. The greatest differences in retention times are seen when the pH of the eluting buffer is less than 4.0 and the buffer contains no KCN.     

Syntheses of cystothiazole A and its stereoisomers: importance of stereochemistry for antifungal activity

The enantiocontrolled total syntheses of all the stereoisomers of a myxobacterial antibiotic, cystothiazole A, are described. The natural syn stereochemistry at the C4-C5 position was controlled by the asymmetric Evans aldol process, whereas the anti relationship was introduced by a modified Evans aldol methodology. Starting with a known aldehyde, the common substrate of the aldol reactions, cystothiazole A and its three stereoisomers were synthesized in 9 steps. All three stereoisomers did not show antifungal activity even at a dosage 2500-fold that of cystothiazole A.     

Enantioselective separation and pharmacokinetic dissipation of cyflumetofen in field soil by ultra‐performance convergence chromatography with tandem mass spectrometry

Little data on the enantioselective separation of cyflumetofen exists, despite the fact that such data are essential to the assessment of the fate and potential toxic effects of cyflumetofen enantiomers. To address this issue, a simple and sensitive method for the enantioselective determination of cyflumetofen enantiomers in soil has been established using ultra performance convergence chromatography tandem triple quadrupole mass spectrometry. The effects of the chiral stationary phases, mobile phase, auto backpressure regulator pressure, column temperature, flow rate of the mobile phase, and compensation pump solvent were evaluated. The proposed method was applied to the study of the pharmacokinetic dissipation of cyflumetofen stereoisomers in soil under greenhouse conditions. The estimated half‐life of cyflumetofen isomers ranged from 12.2 to 13.6 days, and statistically significant enantioselective degradation was observed. This study not only demonstrates that there is an efficient and sensitive method for cyflumetofen enantioseparation, but also provides the first experimental evidence of the pharmacokinetic dissipation of cyflumetofen stereoisomers in the environment.     

Synthesis of optically active vomifoliol and roseoside stereoisomers

A synthesis of optically active vomifoliol stereoisomers 1-4 and their glucosides, roseoside stereoisomers 5-8, was accomplished via alpha-acetylenic alcohol 11a or 11b effectively prepared by an asymmetric transfer hydrogenation of alpha,beta-acetylenic ketone 10. Simultaneous separation of these stereoisomers by HPLC was also performed.     

Control of Vicinal Stereocenters through Nickel-Catalyzed Alkyl–Alkyl Cross-Coupling

Vicinal stereocenters are found in many natural and unnatural compounds. Although metal-catalyzed cross-coupling reactions of unactivated alkyl electrophiles are emerging as a powerful tool in organic synthesis, there have been virtually no reports of processes that generate, much less control, vicinal stereocenters. In this investigation, we establish that a chiral nickel catalyst can mediate doubly stereoconvergent alkyl–alkyl cross-coupling, specifically, reactions of a racemic pyrrolidine-derived nucleophile with cyclic alkyl halides (as mixtures of stereoisomers) to produce vicinal stereocenters with very good stereoselectivity.     

An NMR study of optical isomers in solution

NMR ³¹P-{¹H} spectra of stereoisomeric N - [S - (methylethoxyphosphinyl) - thioglycolyl]valines in solution to reveal association of the molecules, and interaction of the chiral centres. Under fast inter-associate exchange in achiral media, these interactions lead to the following: (i) The chemical shift of the racemic mixture of enantiomers deviates from the shift of the individual species; (ii) the spectra of non-racemic mixtures are doublets; (iii) there are 2ⁿ lines in the spectrum of a mixture containing unequal concentrations of stereoisomers with n asymmetric centres. The integrated intensity ratio is equal to the concentration ratio in all cases. The concept of statistically controlled associate diastereomerism (SCAD) is introduced and the respective formalism is given to describe the spectral effects accompanying variations of temperature and concentration. It is also shown applicable to more complicated cases involving ion exchange of chiral fragments between stereoisomers.     

Isomeric differentiation of green tea catechins using gas-phase hydrogen/deuterium exchange reactions

Hydrogen/deuterium exchange reactions in a quadrupole ion trap mass spectrometer are used to differentiate galloylated catechin stereoisomers (catechin gallate and epicatechin gallate; gallocatechin gallate and epigallocatechin gallate) and the nongalloylated analogs (catechin and epicatechin, gallocatechin and epigallocatechin). Significant differences in the hydrogen/deuterium exchange behavior of the four pairs of deprotonated catechin stereoisomers are observed upon reaction with D(2)O. Interestingly, the nongalloylated catechins undergo H/D exchange to a much greater extent than the galloylated species, incorporating deuterium at both aromatic/allylic and active phenolic sites. Nongalloylated catechin isomers are virtually indistinguishable by their H/D exchange kinetics over a wide range of reaction times (0.05 to 10 s). Our experimental results are explained using high-level ab initio calculations to elucidate the subtle structural variations in the catechin stereoisomers that lead to their differing H/D exchange kinetics.     

高异三尖杉酯碱的合成及其立体异构体的分离鉴定

2-氧代-6-甲基庚酰基三尖杉碱(3)与0-(1-甲氧基异丙基)羟基乙酸甲酯(4)在强碱性试剂二异丙胺锂(LDA)存在下,起亲核加成反应,反应中间体5在室温用酸性丙酮水解,得到一种新的三尖杉酯类生物碱一一高异三尖杉酯碱(6c)及其立体异构体(6a、6b、6d)的混合物,产率56%、通过制备薄层层析分得这四个立体异构体,它们的1H NMR和异三尖杉酯碱及其立体异构体的1H NMR类似,推定了它们的绝对构型。初步药理试验表明,高异三尖杉酯碱及其立体异构体的混合物对白血病L7712的DNA合成有明显的抑制作用。