Chiral Pyridoxal Catalyzed The Biomimetic Asymmetric Aldol Reaction Of Trifluoromethyl Ketone At The ? Position Of Glycine Tert-butyl Ester

?-Hydroxy-?-amino acids and their derivatives display good biological activities and already have many important applications in medicinal chemistry.So far,many methods have been reported for the synthesis of this type of compounds,however,the synthesis often suffered from long synthetic steps,harsh reaction conditions,or environmental pollutions.Therefore,development of an efficient method for the synthesis of?-hydroxy-?-amino acids and their derivatives is still of great significance and highly desirable.In biological systems,the aldol addition of glycine to aldehydes is catalyzed by vitamin B₆-dependent enzymes to directly produce various chiral?-hydroxy-?-amino acids under mild conditions.The coenzyme pyridoxal is the catalytic center for the reaction.In this thesis,we designed and synthesized chiral N-methyl pyridoxals to mimic vitamin B₆-dependent enzymes for biomimetic aldol reactions.With the chiral pyridoxals as the catalysts,we developed asymmetric biomimetic aldol reaction of glycinate and trifluromethyl ketones,to give the corresponding?-hydroxy-?-amino esters in good yields with high diastereo-and enantioselectivities.The studies include the following three parts.?1?Synthesis of chiral N-methyl pyridoxals with biaryl backbones.?2?Optimization of reaction conditions,including solvent,temperature,concentration,and the additive,for the biomimetic aldol reaction of glycinate and trifluromethyl ketones.?3?Substrate screening under the optimal reaction conditions.