手性合成要點緒論課件

1、Principles and Applications of Asymmetric Synthesis CHAPTER 1Introduction The universe is dissymmetrical; for if the whole of the bodies which compose the solar system were placed before a glass moving with their individual movements,the image in the glass could not be superimposed on reality. . . .

2、 Life is dominated by dissymmetrical actions. I can foresee that all living species are primordially, in their structure, in their external forms, functions of cosmic dissymmetry. Louis PasteurBrief history 1801, Hauy :quartz crystals exhibited hemihedral phenomena; 1809, Malus,:quartz crystals coul

3、d induce the polarization of light; 1812, Biot:Right and left forms of quartz crystals rotated the plane of the polarized light in in different directions. 1815. Biot: differences between the rotation caused by quartz crystals and that caused by the solutions of organic compounds1822, John Herschel:

4、 there was a correlation between hemihedralism and optical rotation. 1846-1848, Pasteur:the rotation of polarized light caused by different tartaric acid salt crystals was the property of chiral molecules. 1874. independent publications by J. H. vant Hoff and J. A. Le Bel dated the actual birth of s

5、tereochemistry 1.1 THE SIGNIFICANCE OF CHIRALITY AND STEREOISOMEIC DISCRIMINATION An object is chiral if it cannot be superimposed on its mirrorimage. In such a case, there are two possible forms of the same object, which are called enantiomers, and thus these two forms are said to be enantiomeric w

6、ith each other.Enantiomers:have identical chemical and physical properties in the absence of an external chiral infuence. optical activity:The property of rotating plane-polarized light.stereoisomeric discrimination is very striking in biological systemsFour different behaviors of chiral compounds:(

7、1) only one enantiomer has the desired biological activity, and the other one does not show significant bioactivity; (2) both enantiomers have identical or nearly identical bioactivity; (3)the enantiomers have quantitatively different activity; (4) the two enantiomers have different kinds of biologi

8、cal activity.Example:l-DOPA .for Parkinsons diseaseasymmetry (or chirality) plays an important role in life sciences.Other examples:1.2.1.NomenclatureFischers Convention: R-CHX-R If the X group (usually OH, NH2, or a halogen) is on the right side, the relative configuration is designated D; otherwis

9、e the configuration is designated L.The Cahn-Ingold-Prelog Convention. In the nomenclature system, atoms or groups bonded to the chiral center are prioritized first, based on the sequence rules. (1) An atom having a higher atomic number has priority over one with a lower atomic number; for isotopic

10、atoms, the isotope with a higher mass precedes the one with the lower mass. (2) If two or more of the atoms directly bonded to the asymmetric atom are identical, the atoms attached to them will be compared, according to the same sequence rule. Thus, if there is no heteroatom involved, alkyl groups c

11、an be sequenced as tertiary secondary primary. When two groups have different substituents, the substituent bearing the highest atomic number on each group must be compared first. The sequence decision for these groups will be made based on the sequence of the substituents, and the one containing pr

12、ior substituents has a higher precedence. A similar rule is applicable in the case of groups with heteroatoms. .Central Chirality.Axial Chirality.Planar Chirality.Helical Chirality.Octahedral Structures.Pseudochiral Centers.Different types according to spatial orientation.1.3 DETERMINING ENANTIOMER

13、COMPOSITION enantiomer excess diastereomer excess1.3.2 The Nuclear Magnetic Resonance MethodNuclear Magnetic Resonance Spectroscopy Measured in a Chiral Solvent or with a Chiral Solvating Agent.Nuclear Magnetic Resonance with a Chiral Chemical Shift Reagent.Chiral Derivatizing Agents for Nuclear Mag

14、netic Resonance Analysis.Various chiral derivatizing agents1.3.4 Chromatographic Methods Using Chiral Columns: Gas Chromatography. The method is based on the principle that molecular association between the chiral stationary phase and the sample may lead to some chiral recognition and sufficient res

15、olution of the enantiomers. Liquid Chromatography. If the compound has a high boiling point, or the compound tends to decompose or racemize at high temperature, HPLC using either a chiral stationary phase or a chiral mobile phase would be the choice of separation.1.3.5.Capillary Electrophoresis with

16、 Enantioselective Supporting ElectrolytesElectrophoresis is based on the transport of electrically charged compounds in a gel or a buffer solution under the influence of an electric field.It should be noted that in electrophoresis no mobile phase is used. The method depends on the different migratio

17、n rates of charged enantiomers in a chiral supporting electrolyte.1. X-Ray Diffraction Methods1.4 DETERMINING ABSOLUTE CONFIGURATION2 Chiroptical Methods3 The Chemical Interrelation Method:The chemical interrelation method for determining the absolute configuration of a compound involves the convers

18、ion of this compound to a compound with a known configuration, and then the absolute configuration is deduced from the resulting physical properties, such as optical rotation or GC behavior.4 Prelogs Method:In 1953, Prelog put forward an empirical rule from which the absolute configuration of an optically active secondary alcohol can be deduced. 5 Horeaus Method :based on kinetic resolution.(2) Modified Moshers Method for Determining the Absolute Con-figuration.This method involves converting chiral alcohols (or amines) to their corresponding MTPA esters (or amides), followed