Phosphono amino acids

NMDA receptors at which NMDA and quinolinic acid (QUIN) are selective agonists. NMDA receptors are competitively and very effectively blocked by a number of phosphono amino acids, notably (i -2-amino-5-... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Weigele M, Bohacek R, Jacobsen VA, Macek K, Yang MG, Kawahata NH, Sundaramoorthi R, Wang Y, Takeuchi CS, Luke GP, Metcalf CA III, Shakespeare WC, Sawyer T. Synthesis of phosphono-containing amino acid derivatives and peptides as signal transduction inhibitors. PCT Int Appl W099/24442, 1999. 

Antagonists such as D-(-)-2-amino-5-phosphono-valeric acid (D-AP V), which competitively block NMDA receptors, cause numerous side-effects such as memory impairment, psychotomimetic effects, ataxia and motor dis-coordi-nation, since they also impair normal synaptic transmission. The challenge has therefore been to develop NMDA receptor antagonists that prevent the pathological activation of NMDA receptors but allow their physiological activation. 

Dipeptide and phosphono dipeptide and several amino acids Kryptafix2 (crown ether) HCl in re. ceiving phase Counter-trans- SLM in HF port of CL Stereoselective permeation of 1-1 dipeptide [100]... 

Perkins, M., Rudin, M., Sauter, A., Wiederhold, K.-H., Muller, W. Biphenyl-derivatives of2-amino-7-phosphono-heptanoic acid A novel class of potent competitive N-methyl-D-aspartate receptor antagonists II. Pharmacological characterization in vivo, Neuropharmacology 1996, 35, 655-669. 

The literature data on the preparation of phosphono-dipeptides from 1-aminoalkanephosphonic acids showed 7-7 that the yields of condensation reactions are usually small or moderate. Moreover,the use of bulky N-blocked amino acids drastically decreased the reaction yield. Thus following Martell s method— we wre unsuccesful in the preparation of dipeptides containing N-terminal valine or leucine,while peptides of phenylalanine were obtained in 5—10% yield.Also the active ester method appeared to give small yields of the desired products. Our studies using p-nitrophenyl- and cyanomethyl esters of N-phtaloyl amino acids confirmed these observations. 

Fig. 1.9. EPR spectra of Ti02 colloids modified with alanine (upper) and amino phosphono propionic acid (lower) in the presence of copper ions illuminated with 355 nm laser at 10 K and recorded at different temperatures indicated at the figure.

Glyphosate or N-(phosphono-methyl) glycine Glycine derivative Inhibits amino acid synthesis nonselective, fast-acting herbicides Used as general weed control and weed control in transgenic maize 11-6... 

A new and more amenable synthesis of 2-amino-5-phosphono-pentanoic acid consists in reaction between diethyl... 

Rundstrom. N. etal. (1994) Cyanotriphenylborate Subtype-specific blocker of glycine receptor chloride channels. Proc. Natl. Acad. Sci. USA. 91,8950-8954. Saitoh, T et al. (1994) A novel antagonist, phenylbenzene (O-phosphono-a-amino acid, for strychnine-sensitive glycine receptors in the spinal cord. Br.J. Pharmacol.. 113,165-170. 

The CHF and CF2 groups are superior to CH2 as isosteres of oxygen and this has led to extensive interest in their chemistry. The a-difluorophosphonate analogues of the phosphates of L-serine (219), L-threonine (220), and L-allothreonine (221) have been prepared by highly enantioselective reactions of difluoromethylpho-sphonate carbanion with chiral esters. Lipase PS catalysed acetylation of prochiral 1,3-propandiol alkylphosphonates 222 is reported to be highly enantioselective and the resulting monoacetate enantiomers 223 have been used to synthesise a series of (o-phosphono-a-amino acids, 224 and 225.Other routes to 225, one of... 

ATT. Yokomatsu. T.. Sato. M., and Shibuya. S., Lipase-catalyzed enantioselective acylation of prochiral 2-(co-phosphono)alkyl-L3-propanediols. Application to the enantioselective synthesis of m-phosphono-a-amino acids. Tetrahedron Asymmetry. 7. 2743, 1996. 

Synthesis of Phosphoric Acids and Their Derivatives. - A series of monoalkyl and dialkyl phosphorus acid chiral esters have been synthesised for use as carriers for the transport of aromatic amino acids through supported liquid membranes. The compounds acted as effective carriers but enantio-separation was at best moderate. A range of phosphono- and phosphoro-fluoridates have been prepared by treatment of the corresponding thio- or seleno- phosphorus acids with aqueous silver fluoride at room temperature (Scheme 1). In some cases oxidation rather than fluorination occurred. Stereospecifically deuterium-labelled allylic isoprenoid diphosphates, e.g. (1), have been synthesised from the corresponding deuterium-labelled aldehyde by asymmetric reduction, phosphorylation and Sn2 displacement with pyrophosphate (Scheme 2). ... 

Wahl, P., Anker, C., Traynelis, S.F., Egebjerg, J., Rasmussen, J.S., Krosgaard-Larsen, P., Madsen, U., 1998. Antagonist properties of a phosphono isoxazole amino acid at glutamate RI-4 (R,S)-2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid receptor sub-types. Mol. Pharmacol. 53, 590-596. 

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