Remarkable Potential of the α-Aminophosphonate/Phosphinate Structural Motif in Medicinal Chemistry

<strong>Synthesis of &alpha;-aminophosphonates and related derivatives under microwave conditions</strong>

“…When cyclohexanone was applied as the oxo-reagent, a slightly higher temperature was necessary to furnish the corresponding aminophosphonate derivatives (2). Starting from paraformaldehyde, several compounds containing N-CH2-P moiety (3-6) were also prepared [19][20][21][22][23].…”

“…They are important targets in bio- [1,2], medicinal-[3-6] and pesticide chemistry [7][8][9]. One of the most common synthetic routes towards α-aminophosphonates and α-aminophosphine oxides is the Kabachnik-Fields (phospha-Mannich) reaction, involving the condensation of an amine, an oxo compound and a >P(O)H species, such as a dialkyl phosphite or a secondary phosphine oxide [10][11][12][13].…”

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

“…This is the basis for synthetic applications of these compounds as chiral precursors in several stereospecific transformations [15]. Although, different structures of phosphonic and phosphinic groups compared with the carboxylic function could a priori disrupt enzyme-ligand interactions, they frequently are recognized by enzymes or receptors as inhibitors or false substrates [16,17]. Phosphinopeptides containing C-terminal α-aminophosphinic acids have been prepared by similar methods to those used with their phosphonic analogues, for example the coupling of N-protected amino acids or their active esters with α-aminophosphinates [18], or with free α-aminophosphinic acids in organic or aqueous-organic media has been reported [19].…”

“…Moreover, they can act as simple analogues of amino acids replacing the carboxylic group by the phosphinic moiety, as nonhydrolysable phosphate analogues or as chelating agents of metal ions present in the active site of the enzymes [22]. A number of excellent reviews on various aspects of their activity in natural systems have been published [16,17].…”

“…This is the basis for synthetic applications of these compounds as chiral precursors in several stereospecific transformations [15]. Although, different structures of phosphonic and phosphinic groups compared with the carboxylic function could a priori disrupt enzyme-ligand interactions, they frequently are recognized by enzymes or receptors as inhibitors or false substrates [16,17].…”