An overview of stereoselective synthesis of α-aminophosphonic acids and derivatives

Abstract

An overview of all methodologies published during the last few years focused to the stereoselective (diastereoselective or enantioselective) synthesis of α-aminophosphonic acids and derivatives is reported. The procedures have been classified according a retrosynthetic strategy and taking into account the formation of each one of the bonds connected to the chiral centre. Keywordsα-Aminophosphonic acids; α-Aminophosphonates; Stereoselective Synthesis; Resolution; Chiral Pool Introducciónα-Aminoalkylphosphonic acids 1 are structurally analogous to α-amino acids 2, obtained by isosteric substitution of planar and less bulky carboxylic acid (CO 2 H) by a tetrahedral phosphonic acid functionality (PO 3 H 2 ). Several aminophosphonic, aminophosphinic and aminophosphonous acids have been isolated from various natural sources either as free amino acids or as constituents of more complex molecules. 1 Many natural and synthetic aminophosphonic acids, their phosphonate esters and short peptides incorporating this unit, exhibit a variety of biological properties. 2 Their diverse applications include enzyme inhibitors 3 such as synthase, 4 HIV protease, 5 rennin, 6 phosphatasa activity, 7 PTPases, 8 and potent antibiotics, 9 as antibacterial agents, 10 antiviral, 11 antifungal, 12 herbicides, 13 antitumor agents. 14 Their role for antibody generation is also well documented. 15 In addition, the incorporation of cyclic amino acids of medium ring size into key positions in peptide chains plays an important role, and constitutes the most prominent pathway to conformationally constrained peptidomimetics, a tool in modern drug discovery. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn addition, α-aminophosphonic acids and their monoalkyl esters are also of interest in hydrometallurgy in order to extract metals 17 and in diagnostic medicine as screening agents, once complexed with lanthanides and actinides. 18,19 It is well known that the biological activity of α-aminophosphonic acids and derivatives depends on the absolute configuration of the stereogenic α carbon to phosphorous. 20 For example, (R)-phospholeucine 3 is a more potent inhibitor of leucine aminopeptidase than the S enantiomer, 21 and (S,R)-alafosfalin 4 shows higher antibacterial activity against both Grampositive and Gram-negative microorganisms than the other three diastereoisomers. 22 In view of the different biological and chemical applications of the α-aminophosphonic acids and derivatives, in the last 35 years the development of suitable synthetic methodologies for their preparation in optically pure form has been a topic of great interest in several research groups. In this context, several protocols for efficient asymmetric synthesis of α-aminophosphonic acids and derivatives have emerged in the recent years and several reviews have been published. 23 Now we would like to report herein an update over stereoselective synthesis of α-aminophosphonic acids and derivatives from 1998-2007. The principal synthetic stra...

Synthesis and Application of New, Optically Active Compounds as Catalysts and Ligands in Enantioselective Reactions

“…Catalytic asymmetric reactions constitute one of the most potent and environmentally-friendly methods for introduction of chirality into target molecules. Various efforts using chiral catalysts providing non-racemic α-and β-aminophosphonates were developed in the last decade and have recently been reviewed [56][57][58][59]. Among them, stereoselective P-C and C-C coupling approaches can be considered the most preferred methods.…”

Phosphonomethylated derivatives of dinitroanilines

“…Їх взаємодія з діалкілфосфітами призве-ла до відповідних естерів бензиламінофосфоно-вих кислот (10) (схема 4). Дещо ускладненим ви-явився лише подальший гідроліз отриманих ес-терів до вільних кислот (11). Як цільові кислоти, так і вихідні естери являють собою практично нерозчинні у воді сполуки, і при загальновжива-ному методі гідролізу, кип'ятінні в соляній кис-лоті [11] реакція перебігала в гетерогенній фазі, а в суміші був постійно присутній осад, що утруд-нювало гідроліз і він не доходив до кінця.…”

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]. On the other hand, the optically active α-amino-C-phosphinic acids 3 are also considered as analogues of α-amino acids 2 where now the carboxylic group (CO 2 H) is replaced by a tetrahedral and sterically more demanding phosphinic acid functionality (PO 2 HR ).…”