- One-pot synthesis of N-Cbz-α-aminophosphonic acids
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The paper describes the synthesis of N-protected-α-aminoalkylphosphonic acids, phosphoisosteres of amino acids, from phosphorous acid. A simple, milder and effective one-pot procedure for the amidoalkylation of phosphorous acid in a mixture of acetic anhy
- Vinyukov, Alexei V.,Dmitriev, Maxim E.,Ragulin, Valery V.
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supporting information
p. 437 - 441
(2017/04/03)
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- Inhibition of tRNA-dependent ligase MurM from Streptococcus pneumoniae by phosphonate and sulfonamide inhibitors
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Ligase MurM catalyses the addition of Ala from alanyl-tRNAAla, or Ser from seryl-tRNASer, to lipid intermediate II in peptidoglycan biosynthesis in Streptococcus pneumoniae, and is a determinant of high-level penicillin resistance. Phosphorus-based transition state analogues were designed as inhibitors of the MurM-catalysed reaction. Phosphonamide analogues mimicking the attack of a lysine nucleophile upon Ala-tRNAAla showed no inhibition of MurM, but adenosine 3′-phosphonate analogues showed inhibition of MurM, the most active being a 2′-deoxyadenosine analogue (IC50 100 μM). Structure/function studies upon this analogue established that modification of the amino group of the aminoalkylphosphonate resulted in loss of potency, and modification of the adenosine 5′-hydroxyl group with either a t-butyl dimethyl silyl or a carbamate functional group resulted in loss of activity. A library of 48 aryl sulfonamides was also screened against MurM using a radiochemical assay, and two compounds showed sub-millimolar inhibition. These compounds are the first small molecule inhibitors of the Fem ligase family of peptidyltransferases found in Gram-positive bacteria.
- Cressina, Elena,Lloyd, Adrian J.,De Pascale, Gianfranco,James Mok,Caddick, Stephen,Roper, David I.,Dowson, Christopher G.,Bugg, Timothy D.H.
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experimental part
p. 3443 - 3455
(2009/10/10)
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- A mild and convenient oxidation of H-phosphinic acids
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A new mild and convenient method of oxidation of H-phosphinic to the corresponding phosphonic acids was developed. Conversion of H-phosphinic acids into trivalent trimethylsilyl esters using hexamethyldisilazane, followed by their oxidation with air and subsequent methanolysis allowed obtaining the final compounds in good to excellent yields. The methodology was proved to be particularly useful for N-benzyloxycarbonyl-α-aminophosphinic acids. The scope and limitations of the reaction were additionally tested using a variety of both free and protected amino- and hydroxyphosphinates as substrates.
- Berlicki,Mucha,Kafarski
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p. 1959 - 1962
(2008/09/19)
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- PREPARATION OF BENZYL N-BENZYLOXYCARBONYLAMINOPHOSPHONATES AND -AMINOPHOSPHONITES - THE SCOPE AND LIMITATIONS OF O-BENZYL-N,N'-DICYCLOHEXYLOISOUREA METHOD
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Protection of the amino group of aminophosphonic and aminophosphonous acids with benzyl chloroformate followed by esterification of the N-protected derivatives with O-benzyl-N,N'-dicyclohexyloisoureas is described.The esterification of aminobenzylphosphonic and aminobenzylphosphonous acids was studied in some details in order to discuss the scope and limitation of this procedure.The differences in the reactions of aminoalkylphosphonic and aminoalkylphosphonous acids are pointed out.Key words: Aminobenzylphosphonic and -phosphonous acid, N-benzyloxycarbonyl derivatives, esterification, O-benzyl-N,N'-dicyclohexyloisourea, benzyl N-benzyloxycarbonylaminobenzylphosphonate and phosphonite.
- Mucha, Artur,Kafarski, Pawel,Plenat, Francoise,Cristau, Henri-Jean
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p. 187 - 194
(2007/10/02)
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- THE SYNTHESIS OF CYCLOPHOSPHONODIPEPTIDES
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Dipeptides and cyclodipeptides containing aminoalkyl phosphonyl groups have been synthesized.The geometric isomers of some of them are separated and the molecular structures are confirmed by NMR, IR, MS or X-ray diffraction.
- Chen, Ru-Yu,Dan, Shi-Cain
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- CONVERSION OF AMINO ACIDS AND DIPEPTIDES INTO THEIR PHOSPHONIC ANALOGS; Aminoalkylphosphonic acids and peptides II.
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Acylamino carboxylic acids were degradated by the Hunsdiecker-reaction; the bromo-derivatives were reacted with NaPO(OC2H5)2.Aminophosphonic acids were obtained by acidic hydrolysis, and half-blocked derivatives by the selective removal of masking substituents.Two phosphonopeptides were also prepared by this route.
- Oesapay, George,Szilagyi, Ildiko,Seres, Jenoe
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p. 2977 - 2984
(2007/10/02)
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- An Amidoalkylation of Trivalent Phosphorus Compounds with P(O)H Functions Including Acetic Acid Solutions of PCl3, RPCl2 or R2PCl, Diesters of Phosphorous Acid and Phosphorus-III-Acids
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An amidoalkylation of PCl3 or its organic derivatives in acetic acid solution takes place because equilibrium between AcOH and >P-Cl exist, leading to hydroxychlorophosphines.Those last compounds undergo an amidoalkylation like other nucleophiles.Based on these data, it was shown that an amidoalkylation reaction is usual for all phosphorus compounds with the R2P(O)H system and provides derivatives with the >N-C-P(O)R2 functions.The scope and limitation of these reactions are discussed.
- Oleksyszyn, Jozef
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- Chemical process for the production of α-aminophosphonic acids and peptide derivatives
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The present invention provides a process for the production of physiologically-useful α-aminophosphonic acids and peptide derivatives of the formula: STR1 wherein R and R1 may be the same or different and each can be hydrogen, deuterium or an optionally substituted lower alkyl group, lower alkenyl, lower alkynyl, cycloalkyl, aryl or heterocyclic radical containing one or more oxygen, nitrogen or sulphur atoms and which may be fused to an aromatic ring, a lower alkyl group substituted by a cycloalkyl radical, a lower alkyl group substituted by an aryl radical, a lower alkyl group substituted by a heterocyclic radical as defined above or R and R1 together form a polymethylene chain optionally interrupted by an oxygen, nitrogen or sulphur atom, or R1 represents, together with the C(R)--N2 can be hydrogen, optionally substituted lower alkyl, cycloalkyl, aryl or lower alkyl substituted by a cycloalkyl radical, lower alkyl substituted by a heterocyclic radical containing one or more nitrogen atoms; by a heterocyclic radical containing one or more nitrogen atoms, or R2 together with the C(H)--N residue to which it is attached, may represent the atoms required to complete a heterocyclic radical; and n is 0, 1, 2, 3 or 4; comprising oxidizing, using an oxidizing agent, a compound having the formula: STR2 wherein R, R1, R2 and n have their previous significance, and Z is H or a protecting group usually used for an amino group; and then removing any protecting group.
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