Asymmetric Synthesis - OoCities - Geocities Archive Geocities 不对称合成oocities - GeoCities档案地理.ppt

Asymmetric Synthesis Introduction Outline Introduction Principles Addition to carbonyl compounds α-Substitution using chiral enolates Asymmetric aldol reactions Additions to C=C bonds Reduction and oxidation Rearrangements Hydrolysis and esterification Vancomycin Vancomycin models Definitions Stereospecific reaction A reaction in which the configuration of the substrate influences the configuration of the product, or A reaction in which only a specific isomer reacts, in such a way that its configuration influences the configuration of the product. Stereoselective reaction A reaction in which one specific isomer is formed to a greater extent than any other. Asymmetric synthesis A synthesis in which the stereoisomers of a chiral molecule are formed in unequal quantities. Stereodifferentiation Enantiodifferentiating reaction Differentiation is provided by the reagent or reaction environment, and refers to the reagent’s ability to differentiate between enantiofaces, enantiotopes, or enantiomers. Diastereodifferentiating reaction Reactions are influenced by chirality in the substrate and form diastereomers in unequal quantities. May differentiate between diastereofaces, diastereotopes, or diastereomers. Introduction Biologically active molecules are also chiral Enantiomers possess different types of activity Both are active, have different potencies Both have similar activity Both are active but type of activity is different. Only one enantiomer is active, other is devoid of activity Examples Hypertensive agent L-Methyldopa Propoxyphene – both enantiomers are biologically active. D isomer is an analgesic while L isomer has antitussive property Potential Problems of Enantiomers their Solution In the racemic mixture only half may have beneficial result so the dosage must be increased to reach the therapeutic window one enantiomer may have adverse effect when taken To get pure enantiomers Resolution of the racemate or intermediate in the synthetic route – expensive