Aminoethylphosphonic acids synthesis

A new synthesis (Scheme 4) of 2-aminoethylphosphonic acid (24) has been described in which bis(dimethylamino) phosphorochloridate is condensed with an a-anion derived from an aliphatic nitrile.71 An advantage of this synthesis is that the intermediate (25) can be alkylated, which constitutes the simplest synthesis so far published for substituted aminoethylphosphonic acids. Both C-3 and the phosphorus atom of PEP are incorporated into (24) in Tetrahymena pyriformis,72 which confirms... 

As seen in Scheme 1 a route similar to the biological pathway has now been explored by the independent synthesis of each precursors by chemical means. Work presented in this communication describes the production of synthetic 2-aminoethylphosphonic acids by the controlled reductive amination of 2-oxoalkylphosphonate diesters... 

Kafarski, P., and Mastalerz, P., Synthesis of dipeptides containing P-terminal 2-aminoethylphosphonic acid, Rocz. Chem., 51, 433, 1977. 

The Hofmann degradation is applicable to the synthesis of 2-aminoalkylphosphonic acids." " For example, 2-aminoethylphosphonic acid has been obtained by this method in 75% yield (Scheme 8.94). To avoid the drastic conditions required by the hypobromite method, two new Hofmann-like reagents, iodosobenzene and /-hydroxy-Z-p-tolucnesulfonyloxyiodobcnzcnc (HTIB), have been introduced. Under these conditions, the rearrangement takes place smoothly to produce the desired aminoalkylphosphonic acids in high yields (65-93%). ... 

Barycki, J., Mastalerz, P, and Soroka, M., Simple synthesis of 2-aminoethylphosphonic acid and related compounds. Tetrahedron Lett., 11, 3147, 1970. 

Laboratory synthesis of P-substituted monosaccharides has been carried out (6.853) and (6.854). Interactions between saccharides and phosphonates have been studied and various derivatives isolated [15]. Aminoethylphosphonic acid reacts readily with d-glucose, for example, and undergoes rearrangement to give an aminoketose [16]. 

Hederos M, Konradsson P (2005) Synthesis of the core tetrasaccharide of Trypanosoma cruzi glycoinositolphospholipids Manp(al->6)-Manp(al-> 4)-6-(2-aminoethylphosphonic acid)-GlcNp(al->6)-myo-Ins-l-P04. J Org Chem 70(18) 7196-7207... 

Before 1975, peptides with C-terminal l-aminoalkylphosphonic acid residues (1-APA) or their esters 1 were essentially unknown. In 1978, the antibacterial properties of phospho-nopeptides incorporating C-terminal 1-aminoethylphosphonic and aminomethylphosphonic acids were reported1 1 and this stimulated interest in this class of compounds. Alaphosphalin [2, alaphosphin, l-(L-alanylamino)ethylphosphonic acid] is probably the first example of a rationally designed synthetic antibiotic. Alaphosphalin did not reach the market, however its discovery increased interest in the development of new synthetic methods for the synthesis of l-aminoalkylphosphonic adds as well as their esters and peptides. 

A few methods for the esterification of 1-aminoalkylphosphonic adds have been developed for use when diesters of 1-aminoalkylphosphonic acids are the preferred starting materials for peptide synthesis. 8 In general, 1-aminoalkylphosphonic acids cannot be esterified under conditions that work for amino acids, and protection of the amino group is absolutely essential. Diethyl 1-aminoethylphosphonate [9, Alap(OEt)2] is synthesized from Alap in two steps (Scheme 6). Orthoformates are highly recommended because esterification is almost quantitative. 24 ... 

Isbell, A.R, Berry, J.P., and Tansey, L.W.. Amino phosphonic acids. Part 3. The synthesis and properties of 2-aminoethylphosphonic and 3-aminopropylphosphonic acids, J. Org. Chem.. 37. 4399. 1972. Deschamps, B., Lefebvre, G., and Seyden-Penne, J., Mechanism of Homer-Emmons reaction. Part 1. Reaction of benzaldehyde and phosphonomtriles in tetrahydrofuran. Tetrahedron. 28. 4209. 1972. Buchecker, R., Hamm, P., and Eugster. C.H.. Absolute configuration of xanthphyll (lutein). Helv. Chim. Acta, 57, 631, 1974. 

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