The Synthesis Of Macrocyclic Polyamines And Its Effect On The Lipase Activity

Macrocyclic polyamine compound is a type of excellent ligand,which can be coordinate with metal ions, neutral molecules,organic cations and organic anions. They are widely used in chiral recognition, basic medical research, new materials' research, the mimicry of metalloenzyme and other aspects. Therefore, at present the research of macrocyclic polyamines and their derivatives is still one of the major research topics in chemistry, biology and basic medical research.The macrocyclic amides is a special class of macrocyclic polyamine with amide, which has the dual features of macrocyclic polyamines and oligopeptides.So they have the different coordination properties with other macrocyclic polyamines.These macrocyclic polyamines have a prosperous potential application in catalytic asymmetric synthesis, molecular recognition and the simulation of metalloenzyme. Therefore, the research of macrocyclic amides' synthesis and application has very important theoretical and practical significance.In this paper we designed and synthesised two kinds of macrocyclic amides and carried out the structural modification. We also preliminary researched the effect of these macrocyclic amides and their derivatives on the lipase activity.The main work can be divided into the following sections.In the first chapter, we briefly introduced the research background and the structral features of macrocyclic polyamines.We also simply summarized its application in the molecular recognition, the catalysis of metal complex and the drug research.The significance was also expounded about the synthesis and application of macrocyclic polyamines and their derivatives. We also simply summarized the synthesis of macrocyclic polyamines and chiral macrocyclic polyamines. The main methods about the macrocyclic polyamines are metal ion template, high degree of dilution, Richman and Atkins method, etc. Each method has itsadvantages and disadvantages. But only a few reports about the synthesis of chiral macrocyclic polyamines have appeared. The mainly reasons are the complex synthesis steps and difficult post-processing and the lower yield.In order to facilitate search,We summarized the synthesis methods about chiral macrocyclic polyamines that have been reported. In the second chapter, we mainly presented a simple and convenient approach to the synthesis of macrocyclic polyamines and their derivatives that derived from the natural amino acids.Glycine and L-alanine as the starting material, after several procedures we synthesized two kinds of macrocyclic amides. We obtained eleven kinds of N-substituted derivatives with different side chains. The structures were confirmed by MS and 1~HNMR. In the synthesis process, the N-protection with tosyl chloride was not required and the structure were easily to be modified. Therefore,our research lay a foundation for the future synthesis of macrocyclic compounds.In the third chapter, we preliminary researched the effect of macrocyclic polyamines and their derivatives on the lipase activity. Candida antarctica lipase B has a widely use. Compared with other lipases, CAL-B has a strong stereoselectivity and a high catalytic activity in aqueous and non-aqueous media. In this chapter, using 2-[(2-methyl-6-ethyl) phenyl amino]-propionic acid methyl ester as the template, the CAL-B as the catalyst and macrocyclic polyamines and their derivatives as the additives, we researched the effect on the CAL-B catalyzed hydrolysis of ester.At first, using D,L-lactic acid as the material, we synthesized the 2-[(2-methyl-6-ethyl) phenyl amino]-propionic acid methyl ester. Secondly, we researched the analysis conditions of 2-[(2-methyl-6-ethyl) phenyl amino]-propionic acid on the HPLC. The best conditions are as follows: the column is CHIRALPAK AD-H, the mobile phase is hexane:isopropanol:TFA=97:3:0.05, the flow rate is 1.0 ml/min, the detection wavelength is 254nm, the temperature is 25°C .Finally, using the macrocyclic polyamines and their derivatives as additives, Owe researched the effect on the CAL-B catalyzed hydrolysis of ester. But the results are not optimistic. The effect on the ee value and conversion rate was not great.