Synthesis And Application Of Amino Acid-based Chiral Small Molecule Prodrugs

Chirality plays an important role in the life of animals and plants.All proteins,enzymes and carbohydrates are chiral.Chirality is also crucial in agriculture,pharmaceutical and chemical industries.At present,more than half of the drugs we use are chiral compounds,and the synthesis and separation of chiral compounds are the most important part of drug development.The modification of natural products,the further synthesis of chiral sources,asymmetric catalysis and the resolution of enantiomers play important roles in the separation and synthesis of chiral drugs to varying degrees.Synthesis of chiral drugs from chiral sources and asymmetric catalysis are the most basic and common methods to construct chiral compounds.Amino acids,as the key synthetic precursors of drugs and biological materials,play an important role in the modern pharmaceutical industry.Amino acids can not only be directly used as drugs,but also as necessary chiral structural units in the modification of natural products and their derivatives and the synthesis of new compounds.In addition,amino acids also play an important role in the synthesis of chiral catalysts,such as the synthesis of oxazoline ligands.Oxazoline structures are widely found in some natural products and drug molecules with physiological activities.These compounds have abundant reactivity and are widely used in organic synthesis.Therefore,the synthesis of chiral compounds containing oxazoline structure has broad application and potential in the field of drug synthesis.Based on the advantages of cheap and easy availability and wide application of amino acids,on the one hand,we synthesized a series of phosphinooxazoline drug intermediates that retained their chirality from chiral source-amino acid;on the other hand,chiral phosphinooxazoline was applied to asymmetric catalysis of known reactions to synthesize other chiral drug intermediates.This paper provides two models for the synthesis of chiral drug precursors,one based on the synthesis of chiral sources,and the other based on asymmetric catalysis of chiral catalysts.