Development And Synthesis Of Chiral N-Methylpyridoxal Catalysts: Studies On The Asymmetric Aldol Reaction Of Glycine Esters To Aldehyde

The o-hydroxy amino acids and their derivatives have good biological activity and are key fragments of various active molecules.They have important applications in biomedical and biochemical directions.So far,although many methods have been developed for the synthesis of ortho-hydroxy amino acids and their derivatives,most of the existing synthesis methods are complicated in synthesis steps,unfriendly to the environment,and harsh in reaction conditions,so that the search for more efficient synthesis of o-hydroxy amino acids and their derivatives has been sought.The method is of great significance.In vivo,under the catalysis of vitamin B6 and its coenzymes,the α-carbon of the free amino group-containing compound glycine can be directly added to the electrophile-aldehyde to obtain the o-hydroxy amino acid.The reaction condition is mild and glycine without a protecting group participates directly in the reaction.In this reaction,the active center of the enzyme is vitamin B6,ie pyridoxal/pyridoxamine and its phosphate derivatives.Based on this,the enzymatic system in vivo is simulated and the chiral N-methyl pyridoxal derivative is used as a catalyst to catalyze the addition of the glycine tertbutyl ester to the electrophile-aldehyde to obtain a series of chiral O-hydroxy amino acid derivatives.The catalytic reaction is environment-friendly,mild reaction conditions,and simple operation.It provides a bionic,efficient,and green synthesis route for the synthesis of o-hydroxy amino acids and their derivatives.The main work of this article includes the following aspects:(1)The initial catalyst is used to optimize the reaction conditions,including the optimization of the reaction solvent,the ratio of solvent to water,the equivalent ratio of the substrate,the type of additive,and their equivalents.(2)A series of axially chiral N-methyl pyridoxal catalysts with different side chains were developed and synthesized,and the asymmetric addition reaction of glycine tert-butyl ester to aldehydes was explored.The best catalyst for the reaction.(3)Under the optimum reaction conditions,the aldehydes were extended to the substrate and better reaction results were obtained.The reaction yield was between 35% and 60%,and the product ee value was as high as 87%.(4)A reasonable estimation of this reaction mechanism was made.