Aminophosphonic Acids and Derivatives. Synthesis and Biological Applications

Abstract

In recent years, phosphonic acids and their derivatives have received increasing attention as analogues of a series of naturally occurring phosphates and as "bio-isosteric phosphorus analogues" of amino acids. Unlike a phosphate group, the phosphonate moiety is not readily hydrolyzed, in a biological environment, by the enzymes involved in the phosphate cleavage. This feature makes these compounds extremely useful in several applications, in metabolic regulation, in enhancement or inhibition studies, in the development of potential drugs against several metabolic disorders. The great potential of these compounds in biological applications resulted in an intense effort directed to the development of efficient synthetic methods for their preparation, with particular attention to stereoselective synthesis. The purpose of this review is to give an up-to-date account of the chemistry, the synthesis and the biological activity of aminophosphonic acids and their derivatives.

Stereoselective Synthesis of α-Amino-C-phosphinic Acids and Derivatives

“…These classes of compounds are currently attracting great interest in organic and medicinal chemistry, as well as in agriculture, due to their important biological and pharmacological properties [1][2][3][4][5]. The great importance of this type of compounds has prompted organic chemists to report numerous procedures for their racemic or stereoselective synthesis [6][7][8][9][10][11].…”

Diethyl boronobenzylphosphonates as substrates in Petasis reaction

“…Frequently such efforts appeared successful and resulted in compounds of variable and promising physiological activity and in commercially available substances. [1][2][3][4][5] In addition, aminophosphonic acids and their derivatives are able to form complexes with a variety of metal ions. 6 These findings ensure that they still continue to attract wide interest.…”

In vitro Antitumour Activity, Genotoxicity, and Antiproliferative Effects of Aminophosphonic Acid Diesters and their Synthetic Precursors

“…Much attention and research efforts have concentrated on the study of the synthesis and the biological activi ties of these compounds, because they offer considerable advantages in the development of potential drugs against several metabolic disorders (Orsini et al, 2010). Their negligible mammalian toxicity, the resistance to hydrolysis by proteolytic enzymes, and the structural similarity to the natural amino acids make them extremely attractive for use as antimetabolites (Kafarski and Lejczak, 2000).…”

“…Thus, due to the tetrahedral confi guration at the phosphorus atom, amino phosphonates serve as stable analogues of the unstable tetrahedral carbon intermediates formed in enzymatic processes and therefore act as enzyme inhibitors (Rassukana et al, 2009). Numerous aminophosphonate derivatives are being used as haptens for catalytic antibodies, metabolic regulators, antibiotics, antihypertensive, antiviral and antibacterial agents (Orsini et al, 2010;Palacios et al, 2003). Moreover, some of them inhibit bone resorption, delay the progression of bone metastases, exert direct cytostatic effects on a variety of human tumour cell lines, and have found clinical application in the treatment of bone disorders and cancer (Green, 2000).…”