Peroxidase-catalyzed Synthesis Of Chiral Propargyl Alcohol/amine And Deoxime Reaction Of Oxime Compounds

Chiral propargylic alcohols and propargyl amines are crucial chiral building blocks of organic synthesis.It is of importance structure in many drugs and natural products.Traditionally,these structural units were synthesized by chiral catalysts,which had diverse steps and complicated conditions.Biocatalysis can synthesis chiral compounds with mild conditions,green and high efficiency.Therefore,the article designed chiral propargyl alcohols and propargyl amine compounds of one-pot synthesis of enzymic catalytic reaction,which started from racemic materials.In the first part,the peroxygenase from Agrocybe aegerita can oxidate racemic propargyl alcohols to propargyl ketones with H₂O₂.The optimal reaction conditions were obtained by optimizing the conditions of hydrogen peroxide and enzyme.Substrate spectroscopy studies were then performed and 11 propargyl ketones were successfully reacted with high yield.Finally,propargyl ketones were isolated on a semi-preparative scale.The results showed that the peroxygenase can synthesis of propargyl ketones with high efficiency and green as biocatalyst.In the second part,the(R)-selective alcohol dehydrogenase from Lactobacillus kefir DSM 20587 and the(S)-selective alcohol dehydrogenase from Thermoanaerobacter brockii were successfully cascaded with peroxygenase.The optimal reaction conditions were obtained by optimizing the conditions of enzyme's concentration and cofactor.Substrate spectroscopy studies were then performed and22 chiral propargylic alcohols were successfully reacted with high yield and high enantiomeric excess.The chiral product was confirmed by HPLC.Finally,chiral propargyl alcohols were isolated on a semi-preparative scale.In the third part,(R)-selective amine transaminase from Aspergillus terreus and(S)-selective amine transaminase from Chromobacterium violaceum DSM 30191 were successfully cascaded with peroxygenase.The optimal reaction conditions were obtained by optimizing the conditions of enzyme's concentration,p H and Alanine.Substrate spectroscopy studies were then performed and 8 propargyl amine were successfully reacted with high yield and high enantiomeric excess.The chiral product was confirmed by GC.Finally,chiral propargyl amine were isolated on a semi-preparative scale.In the fourth part,to explore a new green deoximation reaction catalyzed by haloperoxidase,and expand the application scope of deoximation reaction cascaded with alcohol dehydrogenase(ADH).The optimal reaction conditions were obtained by optimizing the conditions of enzyme's concentration,p H and H₂O₂.Under the conditions,seven oximes were employed and the corresponding aldehydes and ketones were obtained smoothly with the yield of 23%-98%.Furthermore,some of the deoximation reactions as mentioned were cascaded with Tg ADH,which finally gave the resultant alcohols.In summary,the new application of two peroxidase were reported as biocatalyst,which provided new idea for the synthesis of key structural units of drug molecules.