Study On The Stereodivergent Reaction Based On Camphor And Resolution To Prepare Optically Pure Amino Acids

In the long process of Earth’s evolution and development,the nature has produced a large number of chiral molecules.However,the amount of many enantiomers of chiral compounds are difference in the natural,and some even only one enantiomer,such as biological macromolecular proteins are only composed of L-amino acids.L-amino acids can be used by organism directly.When D-amino acids are taken into the body,they need to be converted into L-amino acids before they are used or excreted directly.While intaking of D-amino acids excessively may cause the body poisoning.The enantiomers of chiral compounds show great differences in vivo.Chirality is closely related to our lives.The synthesis of chiral compounds is the focus and difficulty in the research of organic chemistry.At present,although many methods have been reported for the preparation of chiral compounds,Stereodivergent reaction and resolution method are two very effective approaches.The Stereodivergent reaction is an efficient and highly selective synthesis of multiple single optically active stereoisomers using a substrate by means of conditions or reagents,which is highly important and valuable in drug discovery.In this paper,a general and facile methodology for temperature-dependent enantiodivergent and diastereodivergent synthesis of amino acids with one or multiple chiral centers was developed.In addition,based on the classical method of resolution,this paper proposes a new resolution method based on the concept of bionics,that is a small molecule compound of organic mimicking an enzyme,just reacting with one isomer in the racemate but without the other to achieve the resolution.The small molecule of organic has a simple structure and species diversity.It is less affected by the structure of the amino acid compared to the enzyme,and it can be widely used for the resolution of various of amino acids.Using camphor as starting material,it was oxidized by selenium dioxide into camphorquinone,reduced to hydroxycamphor with sodium borohydride,reacted with Boc-Gly,and finally cyclized to give tricyclic iminolactone,which was used as a receptor.We studied its alkylation reaction with benzyl bromide,allyl bromide and other halogenated hydrocarbons,Aldol reaction with benzaldehyde and isobutyraldehyde,and asymmetric Micheal addition reaction with ethyl crotonate and tert-butyl crotonate.In the low temperature(-78°C to-40°C)reaction,the endo-side offensive substitution product is obtained,and in the high temperature(-10°C to 25°C)reaction,the substitution product in the exo direction is attacked;2-hydroxycamphor is used as a mimic enzyme.The esterification and cyclization reactions of hydroxycamphor and Boc-protected natural amino acids(Phe,Val,etc)and non-natural amino acids(naphthylalanine),the separation of D-amino acids and L-amino acids using the characteristics of different thermodynamic stability of the products,It has also achieved good research results.