圆二色谱中的激子手性法在有机化学中的应用

激子手性法是圆二色谱领域内,近一、二十年内发展的一种测定有机化合物绝对构型的可靠方法。本文对其基本原理及规律作一简要介绍。并以邻二醇、共轭烯酮,共轭二烯及丙烯醇为例,介绍本法在测定绝对构型中的应用。此外,本法也可用于糖类的结构研究。     

光谱法鉴定手性化合物的绝对构型——从仪器表征到理论计算

手性化合物的结构确定,尤其是新型手性化合物的绝对构型测定一直是不对称研究的重要工作.除单晶测试外,光谱学方法近年来被广泛应用于手性分子结构鉴定,主要包括电子和振动圆二色谱、旋光光谱、旋光拉曼谱等.本文对上述测试方法的原理、应用范围和相关理论计算方法做了介绍.把谱学测试与理论计算相结合,将成为手性分子结构鉴定的重要发展方向.     

5-烷氧基-4-环胺基-3-卤-2(5H)-呋喃酮的合成与表征

在氟化钾作用下,亲核试剂环状仲胺与5-烷氧基-3,4二卤-2(5H)-呋喃酮在室温下发生串联的迈克尔加成-消除反应,合成了17个新化合物.通过旋光度,UV-Vis,IR,1H NMR,13C NMR,MS,元素分析和X射线单晶衍射等表征方法,确定了目标化合物的化学结构和绝对构型.     

水溶液中锌粉促进邻二醇合成的研究

邻二醇是有机合成中重要的合成子,是合成烯烃、酮类化合物的重要中间体,广泛用于农药、医药等精细化工品的合成.合成邻二醇最有效的方法是羰基化合物的还原偶联,通常由羰基化合物与相应的金属试剂或金属络合物作用而实现,往往反应时间长,要求的条件苛刻,有的收率比较低.     

高效液相色谱圆二色检测技术在手性化合物分析中的应用

对近年来高效液相色谱圆二色检测技术在手性化合物分析中的应用进展进行综述,简单介绍了高效液相色谱圆二色检测器的原理和特点,着重介绍了非手性色谱条件下圆二色检测技术在手性化合物对映体纯度测定、复杂基质中手性化合物分析以及在手性化合物绝对构型测定中的应用,并讨论了它的应用前景。     

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.     

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。     

振动圆二色谱在轴手性β-双咔啉N—O衍生物立体化学研究中的应用

采用振动圆二色谱(VCD)方法研究了一个具有高度催化活性的轴手性结构的双咔啉N—O化合物的立体化学结构. 在B3LYP/6-311+G(d)水平上得到的计算结果表明, 对于具有负旋光值的双咔啉N—O化合物化合物, 其绝对构型是aS. 同时, 分别计算了双咔啉N—O化合物的电子圆二色谱(ECD)和旋光值, 并与实验结果进行了比较. 在化合物结构完全正确条件下, VCD, ECD和旋光数据均表明, 具有负旋光值的该化合物的绝对构型是aS.     

手性芳基邻二醇的不对称合成

具有特定功能基团的手性芳基邻二醇是许多具有特殊功能的药物、农药和信息素的重要中间体,近年来手性芳基邻二醇类化合物的合成与应用研究引起了人们的广泛关注。本文从生物催化不对称合成和化学催化不对称合成两方面综述了近年来手性芳基邻二醇的合成进展,概述了前手性底物上取代基的电子效应和空间效应、手性催化剂的种类和反应体系等因素对合成手性芳基邻二醇产率及光学活性的影响,并对手性芳基邻二醇不对称合成的发展趋势进行了展望。     

三甲基溴代硅烷促进的非环状与环状缩醛(酮)的合成

以三甲基溴代硅烷作为反应促进剂, 在室温和原甲酸酯或原乙酸酯存在的条件下, 利用醇、二醇处理羰基化合物, 高收率地实现了一系列非环状与环状缩醛(酮)的合成. 产物结构经1H NMR、元素分析等进行了表征.     

Practical method for the absolute configuration assignment of tert/tert 1,2-diols using their complexes with Mo2(OAc)4

We describe here an application of the practical, simple, and reliable approach for the determination of the absolute configuration of sterically demanding tert/tert vic-diols. According to this method, it is only necessary to mix dimolybdenum tetraacteate and a chiral diol in DMSO and record the CD spectra in the 250-650 nm spectral range. From the sign of the CD bands occurring at around 310, 350, and 400 nm, it is possible to establish the chirality of the diol unit expressed by the sign of the O-C-C-O torsion angle. Because the preferred conformation of the diol in the formed complex is known, we are able to determine the absolute configuration of the carbon atoms in the diol subunit even in flexible tert/tert vic-diols.     

Synthesis of a new chiral oxazolidinone auxiliary based on d-xylose and its application to the Staudinger reaction

The synthesis of a new chiral oxazolidinone auxiliary based on d-xylose is described which is employed in diastereoselective Staudinger-type β-lactam syntheses. Using 2-chloro-1-methylpyridinium iodide as the dehydrating reagent, the reaction of auxiliary tethered acetic acid with acyclic or cyclic imines gave the desired β-lactams in good yields with excellent cis- or trans-selectivity depending on the geometry of the imine. X-Ray structure determination of one of the obtained compounds corroborated the absolute configuration for all cis products.     

Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus

Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in 1 were chemically elucidated in this study. First, four small fragment molecules were prepared from 1 or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2, 4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from 1 by NaIO(4) oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of (3)J(H,H) and (2,3)J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of 1 were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.     

Facile oxidative hydrolysis of acetals to esters using hypervalent iodine(III)/LiBr combination in water

The combination of (diacetoxy)iodobenzene (PhI(OAc)₂, DIB) and lithium bromide (LiBr) efficiently oxidized cyclic and acyclic acetals to the corresponding hydroxyalkyl carboxylic esters and simple esters in good to excellent yields. The merits of this reaction are that it employs commercially available and non-explosive hypervalent iodine(III) reagent, water as the solvent, a short reaction time, and mild reaction conditions.     

Catalytic asymmetric bromination and chlorination of beta-ketoesters

The first general catalytic asymmetric bromination and chlorination of beta-ketoesters has been developed. The reactions proceed for both acyclic and cyclic beta-ketoesters catalyzed by chiral bisoxazolinecopper(II) complexes giving the corresponding optically active alpha-bromo- and alpha-chloro-beta-ketoesters in high yields and moderate to good enantioselectivities. For the optically active chlorinated products the isolated yields are in the range of 88-99 % and the enantiomeric excesses up to 77 % ee, while the optically active brominated adducts are formed in 70-99 % isolated yield and up to 82 % ee. Based on the absolute configuration of the optically active products, the face selectivity for the catalytic enantioselective halogenation is discussed based on a bidentate coordination of the beta-ketoester to the chiral catalyst and a X-ray structure of chiral alpha,gamma-diketoesterenolatebisoxazolinecopper(II) complex.     

The development for the synthesis of chiral acyclic nucleosides and their phosphonates

Acyclic nucleosides and their phosphonates possess significantly antiviral and cytostatic activities. For acyclic nucleosides and their phosphonates, the introduction of a chiral group to their side chain or the absolute configuration of the chiral atom could affect their biological activities obviously. Thus, the asymmetric synthesis of chiral acyclic nucleosides and their phosphonates has received continuous attention. The previous reports mainly focus on employing the chiral pool and chiral auxiliary methods for the synthesis of chiral acyclic nucleosides and their phosphonates. In contrast, the asymmetric catalysis methods for the synthesis of acyclic nucleosides and their phosphonates are still in the beginning. This digest paper will serve to highlight the significant progress that has been made in these areas.     

Determination of Absolute Configuration of Acyclic 1,2‐Diols with [Mo2(OAc)4], Part 2: New Structural Evidence toward a Rationale of the Method: What Remains of [Mo2(OAc)4] in DMSO Solution?

The nature of the CD-active species obtained by mixing dimolybdenum tetraacetate and a chiral 1,2-diol in DMSO has been studied by different techniques (1D and 2D (1)H NMR, CD, UV/Vis) with two substrates, (R)-phenyl-1,2-ethanediol (1) and (R,R)-butane-2,3-diol (2). The diol/dimolybdenum adducts have diagnostic CD spectra whose sign correlates with the absolute configuration of the organic substrate. It is demonstrated that, in DMSO solution, the acetate ligands of [Mo(2)(OAc)(4)] dissociate to a large extent under the action of the dissolved water, yielding acetic acid and a polyhydrated dimolybdenum species. Addition of a 1,2-diol leads to chelation with formation of one main active species for 2 and two for 1, all with 1:1 stoichiometries at diol/dimolybdenum molar ratios less than 1.5. Only a small fraction (less than 20 %) of the 1,2-diol is bound. The structures of the active complexes are estimated on the basis of NMR spectra, by correlating the observed chemical shifts with the quadruple bond diamagnetic anisotropy. In the predominating complexes for 1 and 2, the 1,2-diol moiety bridges the Mo(2) core forming a six-membered ring.     

(18-Crown-6)-2,3,11,12-tetracarboxylic acid as a chiral NMR solvating agent for determining the enantiomeric purity and absolute configuration of β-amino acids

(18-Crown-6)-2,3,11,12-tetracarboxylic acid is an excellent chiral NMR solvating agent for cyclic β-amino acids and acyclic derivatives with aliphatic, aromatic, and heterocyclic aromatic moieties. The β-amino acids are mixed with the crown ether in methanol-d₄ in either their neutral or protonated form. Substantial enantiomeric discrimination typically occurs for the resonances of the α-methylene and β-methine hydrogen atoms. Resonances of the substituent group of the β-amino acid often exhibit enantiomeric discrimination. The enantiomeric discrimination of the α-methylene and β-methine resonances of specific groups of compounds shows consistent patterns that correlate with the absolute configuration.     

The use of MPA amide for the assignment of absolute configuration of a sterically hindered cyclic secondary amine by 'mix and shake' NMR method

We present here a new method using methoxyphenylacetic acid (MPA) as the chiral derivatizing agent (CDA) for the assignment of absolute configuration of cyclic secondary amines. The MPA amides were prepared using the purification-free 'mix and shake' method. A detailed conformational analysis for the two diastereomeric amides was conducted by 2D NMR experiments and molecular mechanics calculations. We have established that, in the most stable conformation of each syn rotamer of MPA amides, the H-alpha in the MPA moiety is oriented toward the bulky substituent group at the asymmetric carbon in the chiral amine, presumably to avoid steric and/or electrostatic interactions. The observed NMR data were correlated with the conformational model to allow unambiguous assignment of absolute configuration of secondary amines. The results demonstrate that the MPA can be used as a useful CDA in the case of sterically crowded cyclic secondary amines from which the MTPA amides are usually difficult to make.     

NMR determination of absolute configuration of butenolides of annonaceous type

We report herein the first determination of the absolute configuration of the annonaceous butenolides by a NMR method. This technique uses a chiral solvating agent (CSA), the so-called Pirkle's reagent, at low temperature and low concentration, allowing one to apply this method to other natural products as well. Indeed, the presence of basic sites (e.g. tetrahydrofuran, hydroxyl) did not interfere with the major solvation of the reagent with the lactone moiety. A new model is proposed which allowed us to confirm the (S) absolute configuration of the butenolide of annonaceous acetogenins. Furthermore this method can be successfully applied to the measure of the diastereomeric (or enantiomeric) excess of the same butenolide containing compounds.