Development Of Cyclohexanediamine-derived Pyridoxal Quaternary Ammonium Salt Catalyst And Its Biomimetic Catalyzed Asymmetric Addition Of Glycine Ester To Imine

As a kind of amino acids,chiral α,β-diamino acids are chemically and biologically important compounds with wide applications in many areas.The synthesis of α,β-diamino acids is still a challenge in organic synthesis and it is highly desirable to develop efficient and environment-friendly synthetic methods.In biological system,Vitamin-B6-based enzymes can catalyze direct aldol addition of glycine to aldehydes to form chiral β-hydroxy-?-amino acids.Inspired by the biological process,we focused on biomimetic asymmetric Mannich addition of glycine ester to imines to prepare chiral α,β-diamino acids by using N-quarternized chiral pyridoxals as the catalyst.The studies include the following several parts.(1)By introducing chiral cyclohexanediamine as the chiral control element,we developed a class of new chiral N-quarternized chiral pyridoxals with different side arms.The N-quarternized chiral pyridoxals are catalytically active for asymmetric Mannich addition of glycine ester to imines.(2)The reaction parameters including catalyst,solvent,the amount of water,and base were systematically investigated for the asymmetric Mannich addition of glycine ester to imines.(3)Under the optimized conditions,substrate scope was investigated.A variety of chiral β-hydroxy-?-amino acid esters were obtained in 39%-98% yields with 45%-71% ee’s and moderate diastereoselectivity.