Direct Synthesis of 1-Aminoalkanephosphonic and 1-Aminoalkanephosphinic Acids from Phosphorus Trichloride or Dichlorophosphines

Oleksyszyn, Józef; Tyka, R.; Mastalerz, Przemyslaw

doi:10.1055/s-1978-24792

Cited by 55 publications

(17 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compounds used in this study were synthesized as described previously. Racemic 1-aminoalkanephosphonic acids were obtained using either Oleksyszyn or modified Arbuzov methodologies (24,28). Enantiomerically pure or diastereomer pairs of 1-aminoalkylphosphonates were synthesized using the Hamilton-Walker reaction (22).…”

Section: Methodsmentioning

confidence: 99%

Chemical Target Validation Studies of Aminopeptidase in Malaria Parasites Using α-Aminoalkylphosphonate and Phosphonopeptide Inhibitors

Cunningham

Drąg

Kafarski

et al. 2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

During its intraerythrocytic phase, the most lethal human malarial parasite, Plasmodium falciparum, digests host cell hemoglobin as a source of some of the amino acids required for its own protein synthesis. A number of parasite endopeptidases (including plasmepsins and falcipains) process the globin into small peptides. These peptides appear to be further digested to free amino acids by aminopeptidases, enzymes that catalyze the sequential cleavage of N-terminal amino acids from peptides. Aminopeptidases are classified into different evolutionary families according to their sequence motifs and preferred substrates. The aminopeptidase inhibitor bestatin can disrupt parasite development, suggesting that this group of enzymes might be a chemotherapeutic target. Two bestatin-susceptible aminopeptidase activities, associated with gene products belonging to the M1 and M17 families, have been described in blood-stage P. falciparum parasites, but it is not known whether one or both are required for parasite development. To establish whether inhibition of the M17 aminopeptidase is sufficient to confer antimalarial activity, we evaluated 35 aminoalkylphosphonate and phosphonopeptide compounds designed to be specific inhibitors of M17 aminopeptidases. The compounds had a range of activities against cultured P. falciparum parasites with 50% inhibitory concentrations down to 14 M. Some of the compounds were also potent inhibitors of parasite aminopeptidase activity, though it appeared that many were capable of inhibiting the M1 as well as the M17 enzyme. There was a strong correlation between the potencies of the compounds against whole parasites and against the enzyme, suggesting that M17 and/or M1 aminopeptidases may be valid antimalarial drug targets.

show abstract

Section: Methodsmentioning

confidence: 99%

Chemical Target Validation Studies of Aminopeptidase in Malaria Parasites Using α-Aminoalkylphosphonate and Phosphonopeptide Inhibitors

Cunningham

Drąg

Kafarski

et al. 2008

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…8−10 For example, the condensations of benzyl carbamate, aldehydes, and dialkyl monochlorophosphite afforded N-Cbz protected symmetric α-aminoalkylphosphonate diesters. 9 The condensations of benzyl carbamate, aldehydes, aromatic cyclic monochlorophosphite, and 2-chloro-benzo [1,3,2]dioxaphosphole afforded N-Cbz protected symmetric cyclic α-aminoalkylphosphonate diesters, benzyl N-[ (2-oxido-benzo [1,3,2]dioxaphosphol-2-yl)phenylmethyl]carbamate. 8 The reaction of benzyl carbamate, aldehydes, and 2-chloro-1,3,2-dioxaphospholane, an aliphatic cyclic monochlorophosphite, was (Table I, columns 2 and 3).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Mass Spectrometry of 2-Hydroxyethyl 1-Aminoalkylphosphonates

Cai

Yin

et al. 2007

Phosphorus, Sulfur, and Silicon and the Related Elements

View full text Add to dashboard Cite

show abstract

“…4 Yields of single products in crude solid were: 24% of compound 6 (δ = 13.43 ppm), 18% of compound 4 (δ = 15.29 and 15.30 ppm, (84:16 molar ratio)); 8% of compound 8 (δ = 19.01 ppm) and 10% of compound 7 (δ = 22.24 ppm). Fractional crystallization afforded 1-aminocyclohexanephosphonic acid (7) and 4-amino-4-phosphonocyclohexanenecarboxylic acid (4), which physicochemical data are in accordance with the literature.…”

Section: Reaction Of Ethyl 2-oxocyclohexanecarboxylate As Substratementioning

confidence: 97%

“…Fractional crystallization afforded 1-aminocyclohexanephosphonic acid (7) and 4-amino-4-phosphonocyclohexanenecarboxylic acid (4), which physicochemical data are in accordance with the literature. 4 …”

Section: Reaction Of Ethyl 2-oxocyclohexanecarboxylate As Substratementioning

confidence: 99%

Amidoalkylation of Phosphorus Trichloride with Acetamide and Functionalized Cyclic Ketones-Evidence of Dominating Role of Side-Reactions

Dziuganowska

Andrasiak

Ślepokura

et al. 2014

Phosphorus, Sulfur, and Silicon and the Related Elements

View full text Add to dashboard Cite

The course of the reaction between phosphorus trichloride, acetamide and ethyl oxoalkanecarboxylates was studied in terms of the production of side-products. When ethyl 2-oxocycloalkane-and 4-oxocyclohexanecarboxylates were used as substrates, not only mixtures of the expected products-aminophosphonocycloalkanecarboxylic acids and their ethyl esters but AMIDOALKYLATION OF PHOSPHORUS TRICHLORIDE WITH ACETAMIDE 1069 substrate and solvent with phosphonylating agent) were observed. Ethyl 2-oxocyclooctanecarboxylate afforded the expected 2-amino-2-pohosphonocyclooctanecarboxylic acid in minute amounts. For comparison reactions of 1-butyloxocarbonyloxopiperidines afforded the desired aminopiperidinephosphonic acids in good yields and without formation of side-products.

show abstract

Direct Synthesis of 1-Aminoalkanephosphonic and 1-Aminoalkanephosphinic Acids from Phosphorus Trichloride or Dichlorophosphines

Cited by 55 publications

References 0 publications

Chemical Target Validation Studies of Aminopeptidase in Malaria Parasites Using α-Aminoalkylphosphonate and Phosphonopeptide Inhibitors

Chemical Target Validation Studies of Aminopeptidase in Malaria Parasites Using α-Aminoalkylphosphonate and Phosphonopeptide Inhibitors

Synthesis and Mass Spectrometry of 2-Hydroxyethyl 1-Aminoalkylphosphonates

Amidoalkylation of Phosphorus Trichloride with Acetamide and Functionalized Cyclic Ketones-Evidence of Dominating Role of Side-Reactions

Contact Info

Product

Resources

About