Update 1 of: α,β-Diamino Acids: Biological Significance and Synthetic Approaches

Abstract

The discovery of nonproteinogenic amino acids among natural products, either in native state or as fragments of complex molecules, has increased the level of interest in this family of molecules from different scientific standpoints. Compounds with valuable biological properties can be found among these atypical amino acids. In addition, they have served as building blocks for the synthesis of new molecules or as surrogates of native amino acids in known peptidic entities to modulate their biological behavior.

In this context, α,β-diamino acids and their derivatives esters and amides, have attracted a great deal of attention among organic chemists and biochemists through the years. This interest has been due to the ubiquitous nature of α,β-diamino acids as key structural fragments of biologically active compounds. Beyond this focus, the simplest compound, 2,3-diaminopropionic acid, has recently found application in the environmentally safe production of hydrogen for fuel cells, as a selective carrier of CO2 through gel membranes. Also, it has served to assemble a molecular device that produces propelling motion upon IR irradiation and, lately, in the context of food chemistry, 2,3-diaminopropionic acid has been identified as an inhibitor of polyphenol oxidase, the enzyme responsible for the browning of fruits and vegetables and as an enhancer of Maillard browning. In spite of the incidence of these molecules in an increasing number of areas, this review will deal with the biological significance, the therapeutic uses, and other interesting applications of α,β-diamino acids and their derivatives found in the existing literature.

Additionally, aside from the above considerations, the structural complexity of these molecules, having two vicinal chiral centers has also represented a challenge for synthetic organic chemists, especially the synthesis of enantiopure materials. Therefore, the aim of this article will also be to provide a deep and general view of the existing methodology for the synthesis of aliphatic α,β- or 2,3-diamino acids and their simple derivatives, esters, or amides. Among the compounds considered in this review, either of the amino groups can be acylated or contained within a heterocyclic structure. Cyclic analogues such as imidazolidines and piperazines will be included in the article; however, aziridines and 3-amino-β-lactams will be out of the scope of this review and will be only considered as intermediates in the synthesis of acyclic derivatives since extensive revisions of their chemistry already exist in the literature.