Synthesis Of 3,3-diaminopropionic Acid And Its Derivatives

Amino acids are the most basic structural units and physiologically active substances in organic living organisms.They are the basic units that make up the biological proteins and play a vital role in human life activities.Amino acids and their derivatives have a wide range of applications in the production of food,animal feed and medicine industries.Therefore,the synthesis and development of amino acids and their derivatives has always been a research hotspot.3,3-diaminopropionic acid derivatives have a wide range of applications because of its specificity of their structure.Such as,its ?-amino acid structural properties can be developed many uses in the aspects of medicinal.First,with the ?-amino acid to participate in the design of peptide drugs can extend the role of time and improve efficacy.Followed,3,3-diaminopropionic acid derivatives as a transit group and the original drug connected to participate in the design of their predecessors,which can change the physical and chemical properties of the original drug to improve efficacy or reduce toxicity.In addition,the nature of the structural properties of methylene diamine derivatives can also be used with transition metals to form metal organic compounds that develop coordination catalysis.So it is of practical significance to study its synthetic method and improve the synthetic route.Based on the wide application of 3,3-diaminopropionic acid derivatives in medicine and organic synthesis.In the second chapter,we use L-aspartic acid as raw material,and ?-carboxyl group was selectively methylated,then Boc protected amino,?-carboxyl groups are azide to give ?-acyl azide compounds.?-amino acids with side chains with reactive isocyanate groups are obtained by Curtius rearrangement under heating.Then isocyanate was reacted with water and benzyl alcohol to produce substituted urea and N-Boc,N'-Cbz-3,3-diaminopropionic acid methyl ester,respectively.The latter is a special gem-diamino acid derivative which having a different protecting group.This amino acid derivative can be optionally deprotected to give methyl N-Cbz-3,3-diaminopropionate and methyl N-Boc-3,3-diaminopropionate.They are ?-amino acids with one amino group free and the other amino groups with different protecting groups,which can be used in the synthesis of peptides.In the third chapter,the isocyanate was reacted with imidazole to produce N-substituted carbonyl imidazole,and then form side chain with formamide ?-amino acid under the reduction of sodium borohydride.The survey found that this is a new method of synthesizing formamide without reporting.Formamide is an important class of compounds which has a wide range of applications in medicine and organic chemistry.In addition,the formyl group is a conventional amino protecting group especially in peptide synthesis.Based on this,we synthesized the intermediate N-substituted carbonyl imidazole with amine,isocyanate or carboxylic acid as raw materials,and then synthesized 22 other formamide derivatives according to this method,which proves that the method has universal applicability.This method is suitable for the N-Boc protected amino acid or peptide feedstock compared to conventional methods.In addition,our method is economical and no expensive catalyst or special reagent is employed.Moreover,the reaction is simple,mild,fast and shows good applicability.