1606-75-3Relevant academic research and scientific papers
Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate decarboxylase from Bacteroides fragilis
Pallitsch, Katharina,Rogers, Megan P.,Andrews, Forest H.,Hammerschmidt, Friedrich,McLeish, Michael J.
, p. 4368 - 4374 (2017)
Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal abscesses and is involved in 90% of anaerobic peritoneal infections. Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component of the cell wall of B. fragilis. As such PnPDC is a possible target for therapeutic intervention in this, and other phosphonate producing organisms. However, the enzyme is of more general interest as it appears to be an evolutionary forerunner to the decarboxylase family of ThDP-dependent enzymes. To date, PnPDC has proved difficult to crystallize and no X-ray structures are available. In the past we have shown that ThDP-dependent enzymes will often crystallize if the cofactor has been irreversibly inactivated. To explore this possibility, and the utility of inhibitors of phosphonate biosynthesis as potential antibiotics, we synthesized phosphonodifluoropyruvate (PnDFP) as a prospective mechanism-based inhibitor of PnPDC. Here we provide evidence that PnDFP indeed inactivates the enzyme, that the inactivation is irreversible, and is accompanied by release of fluoride ion, i.e., PnDFP bears all the hallmarks of a mechanism-based inhibitor. Unfortunately, the enzyme remains refractive to crystallization.
Synthesis of phosphonated carbocyclic 2′-oxa-3′-aza- nucleosides: Novel inhibitors of reverse transcriptase
Chiacchio, Ugo,Balestrieri, Emanuela,Macchi, Beatrice,Iannazzo, Daniela,Piperno, Anna,Rescifina, Antonio,Romeo, Roberto,Saglimbeni, Monica,Sciortino, M. Teresa,Valveri, Vincenza,Mastino, Antonio,Romeo, Giovanni
, p. 1389 - 1394 (2005)
Phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2′-oxa- 3′-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.
New preparation of diethyl methylformyl-2-phosphonate dimethylhydrazone: A reagent for aldehyde homologation
Petroski, Richard J.
, p. 63 - 66 (2011)
The phosphonate reagent diethyl methylformyl-2-phosphonate dimethylhydrazone contains a protected aldehyde group instead of the usual ester group. It can be used for the two-carbon homologation of aldehydes toαβ, -unsaturated aldehydes. The reagent can be prepared in good overall yield (82%) and purity by deprotection of commercially available diethyl-2,2-(diethoxy)ethylphosphonate with p-toluenesulfonic acid in 1.5% aqueous acetone to give diethyl formylmethyl-2-phosphonate, followed by a simple preparation of the dimethylhydrazone derivative with N,N-dimethylhydrazine. Copyright
Preparation method of diethyl (formylmethyl) phosphonate
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Paragraph 0053; 0060-0064; 0071-0075; 00582-0085, (2019/07/04)
The invention discloses a preparation method of diethyl (formylmethyl) phosphonate, which comprises the following steps: under the protection of inert gas, tetraethyl methylene disphosphonate is mixedwith a reaction solvent, carbanion is generated under the action of a base, and HWE condensation reaction is carried out with ethyl formate to obtain 2-ethoxy vinyl phosphonate diethyl ester; hydrolysis reaction: diethyl (formylmethyl) phosphonate is synthesized by hydrolysis of 2-ethoxy vinyl phosphonate diethyl ester under acidic conditions in the airtight condition. The preparation method of the invention is simple and easy to obtain reaction raw materials, and can be used for obtaining diethyl (formylmethyl) phosphonate by an industrialized method.
Determination of the Absolute Configuration of (?)-Hydroxynitrilaphos and Related Biosynthetic Questions
Pallitsch, Katharina,Happl, Barbara,Stieger, Christian
, p. 15655 - 15665 (2017/10/09)
The ongoing search for bioactive natural products has led to the development of new genome-based screening approaches to identify possible phosphonate producing microorganisms. From the identified phosphonate producers, several until now unknown phosphonic acid natural products were isolated, including (hydroxy)nitrilaphos (4 and 5) and (hydroxy)phosphonocystoximate (7 and 6). We present the synthesis of phosphonocystoximate via an aldoxime intermediate. Chlorination and coupling with methyl N-acetylcysteinate furnished 6 after global deprotection. The obtained experimental data confirm the previously assigned structure of the natural product. We were also able to determine the absolute configuration of (?)-hydroxynitrilaphos. Chiral resolution of diethyl cyanohydroxymethylphosphonate (24) with Noe's lactol furnished both enantiomers of 4. Conversion of (+)-24 to (R)-2-amino-1-hydroxyethylphosphonic acid by reduction of the cyano-group showed (?)-hydroxynitrilaphos ultimately to be S-configured. Further, we present a 13C-isotope labeling strategy for 4 and 5 that will possibly solve the question of whether hydroxynitrilaphos is a biosynthetic intermediate or a downstream product of hydroxyphosphonocystoximate biosynthesis.
Process for Preparing Cinacalcet and Pharmaceutically Acceptable Salts Thereof
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Paragraph 0093, (2015/10/05)
The present patent application relates to a process for preparing, cinacalcet or a pharmaceutically acceptable salt thereof, which comprises reacting 3-trifluoromethylbenzaldehyde having the following formula (II) with the phosphorus-comprising derivative having the following formula all) in which R1 and R2, which may he identical or different, are each a (C1-C6)alkyl group. The present invention also relates to the phosphorus-comprising derivative having the formula (III), to the use thereof and to the process for preparing same. The present invention also relates to the phosphate salt of cinacalcet and to uses thereof.
A new route to α-carbolines based on 6π-electrocyclization of indole-3-alkenyl oximes
Markey, Sophie J.,Lewis, William,Moody, Christopher J.
supporting information, p. 6306 - 6308 (2014/01/17)
Indoles are converted into α-carbolines in four steps by acylation at C-3, Boc-protection, olefination of the resulting 3-indolyl aldehydes or ketones to give N-Boc-3-indolyl alkenyl oxime O-methyl ethers, which upon heating to 240 C under microwave irradiation undergo loss of the Boc-group, and 6π-electrocyclization to α-carbolines, following aromatization by loss of methanol (11 examples, 30-90% yield).
Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
Clinch, Keith,Crump, Douglas R.,Evans, Gary B.,Hazleton, Keith Z.,Mason, Jennifer M.,Schramm, Vern L.,Tyler, Peter C.
, p. 5629 - 5646 (2013/09/02)
The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme.
Modifications around the hydroxamic acid chelating group of fosmidomycin, an inhibitor of the metalloenzyme 1-deoxyxylulose 5-phosphate reductoisomerase (DXR)
Zingle, Catherine,Kuntz, Lionel,Tritsch, Denis,Grosdemange-Billiard, Catherine,Rohmer, Michel
supporting information, p. 6563 - 6567,5 (2012/12/12)
Fosmidomycin derivatives in which the hydroxamic acid group has been replaced by several bidentate chelators as potential hydroxamic alternatives were prepared and tested against the DXR from Escherichia coli. These results illustrate the predominant role
Modifications around the hydroxamic acid chelating group of fosmidomycin, an inhibitor of the metalloenzyme 1-deoxyxylulose 5-phosphate reductoisomerase (DXR)
Zinglé, Catherine,Kuntz, Lionel,Tritsch, Denis,Grosdemange-Billiard, Catherine,Rohmer, Michel
supporting information, p. 6563 - 6567 (2013/01/14)
Fosmidomycin derivatives in which the hydroxamic acid group has been replaced by several bidentate chelators as potential hydroxamic alternatives were prepared and tested against the DXR from Escherichia coli. These results illustrate the predominant role
