Study On Cyclization Reaction And The Controllable Selectivity Of Aminoalcohols

The majority of pharmaceuticals and biologically active compounds are heterocycles.Simple,convenient protocols in the synthesis of heterocycles play an important role in the synthesis of heterocycles.And enzymatic methods had been more and more widely used in organic chemistry,which have potential in the selective enzymatic synthesis of biological activity compounds.In this thesis,the synthesis of heterocycles by direct cyclization and the controllable selective enzymatic synthesis of aminoalcohol derivatives were developed.The preparation of aminoalcohols fromα-amino acids and their derivatives use of convenient reduction were applied.The synthesis of theγ-aminoalcohols was start from aldehyde derivatives using one pot reaction of three components.Then the intermediate products were reduced with NaBH₄/I₂ to giveγ-aminoalcohols with a good yield.A simple and efficienct method in the synthesis of eight-membered heterocycles by direct cyclization of aminoalcohol derivatives was explored.The direct cyclization of aminoalcohol derivatives with divinyl dicarboxylates gave novel heterocycles beating both lactone and lactam functional groups.The influences of the reaction conditions and substarte structure on the direct cyclization were systematically investigated.The selective enzymatic synthesis of aminoalcohol derivatives containing hydroxyl and amidogen in non-aqueous media was developed. 2-Amino-2-phenyl-ethanol,2-amino-3-phenyl-propan-1-ol and 2-amino-3(4-chloro-phenyl)-propan-1-ol were chosen as substrates.Divinyl dicarboxylates with different length of carbon chain were used as acyl donor.Catalysis by lipase acrylic resin from Candida Antarctica(CAL-B)in acetone could facilitate the single step synthesis of O-acylaminoalcohol derivatives in moderate yields.While catalysis by Acylase "Amano" from Aspergillus oryzae(AA)in DMSO,the N-acylaminoalcohol derivatives were achieved in high yields.Moreover,the influence factors of enzymatic synthesis such as enzyme sources,reaction media,reaction time,temperature were investigated.In this thesis,45 aminoalcohol derivarives and heterocycles were synthesized. These compounds were characterized by ¹H NMR,¹³C NMR,FTIR and ESI-MS and 32 compounds have been confirmed to be new compounds.