- Synthesis of potential inhibitors of the enzyme pantothenate synthetase
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Three phosphinate salts (5), (6) and (7) were prepared as potential inhibitors of the enzyme pantothenate synthetase. The synthesis of compound (5) utilises a (diethoxymethyl)-protected phosphinate (8) as a new reagent for the formation of unsymmetrical phosphinic acids and esters. Initial P-alkylation of (8) followed by a selective deprotection sequence yields intermediate P-H phosphinates (16) and (21) which can be P-alkylated a second time. Enzyme assays have been performed with the target compound and the results are discussed.
- Baillie, Alister C.,Cornell, Clive L.,Wright, Brian J.,Wright, Kenneth
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Read Online
- Synthesis of unnatural 2- and 3-deoxyfuranose analogues
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This Letter describes the synthesis of two racemic analogues of unnatural 3′-deoxy and 2′-deoxy sugars, where a phosphorus atom replaces the carbon atom in the 2′- or 3′-position. Two methods of four- and 5-steps were developed affording these new unnatur
- Dayde, Bénédicte,Pierra, Claire,Gosselin, Gilles,Surleraux, Dominique,Ilagouma, Amadou Tidjani,Van Der Lee, Arie,Volle, Jean-No?l,Virieux, David,Pirat, Jean-Luc
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supporting information
p. 3706 - 3708
(2014/06/23)
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- Rapid and efficient synthesis of unsymmetrical phosphinic acids r′t(o)ohr″
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A new synthesis of unsymmetrical phosphinic acids R′P(O)OHR″ has been evaluated, The first P-C bond was formed by base-promoted H-phosphinate alkylation of a protected H-phosphinate, which is easier and safer to handle, A onepot methodology was developed for the second P-C bond formation reaction that: involves the sila-Arbuzov reaction. This methodology was then extended to the synthesis of a dialkylphosphinic acid with an amino functionality.
- Fougere, Cecile,Guenin, Erwann,Hardouin, Julie,Lecouvey, Marc
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experimental part
p. 6048 - 6054
(2010/03/02)
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- NEW PHOSPHORUS CONTAINING HETEROCYCLIC COMPOUNDS, SUGAR ANALOGUES, AND COMPOSITIONS HAVING ANTI-CANCER ACTIVITY CONTAINING THE SAME
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The invention provides new anticancer compounds of formula (1) such as defined in the present description. The invention also provides pharmaceutical compositions to be used in human or veterinary medicine, comprising at least one compound of formula (1). The present invention further relates to a compound of formula (1) such as defined in the present description, for use as a drug. The invention further relates to the use of a compound of formula (1) for manufacturing a human or animal anticancer pharmaceutical composition.
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Page/Page column 27-28
(2009/03/07)
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- Synthesis of P,N-heterocycles from ω-amino-H-phosphinates: Conformationally restricted α-amino acid analogs
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(Chemical Equation Presented) P,N-Heterocycles (3-hydroxy-1,3- azaphospholane and 3-hydroxy-1,3-azaphosphorinane-3-oxide) are synthesized in moderate yield from readily available ω-amino-H-phosphinates and aldehydes or ketones via an intramolecular Kabachnik-Fields reaction. The products are conformationally restricted phosphinic analogs of α-amino acids. The multigram-scale syntheses of the H2N(CH2) nPO2H2 phosphinic precursors (n = 1, 2, 3) and some derivatives are also described.
- Queffelec, Clemence,Ribiere, Patrice,Montchamp, Jean-Luc
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supporting information; experimental part
p. 8987 - 8991
(2009/04/11)
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- A concise and first synthesis of α-aminophosphinates with two stereogenic atoms leading to optically pure α-amino-H-phosphinic acids
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A highly stereoselective synthesis of ω-aminophosphinates by nucleophilic attack of ethyl diethoxymethylphosphinate to Ellman's N-(tert-butanesulfinyl) ketimines by using Rb2CO3 as a base at room temperature was reported. In the first set of experiments, (S)-(tert-butane-sulfinyl)methyl (p-bromo)phenylketimine (1j) was used as the model compound to study its reaction with ethyl diethoxymethyl-phosphinate. Ethyl diethoxymethyiphosphinate and Rb2CO3 in CH 2Cl2 were placed in a 20 ml, Schienk flask and (5)-N-tert-butanesulfinylketimines 1 were then added at room temperature. The mixture was then stirred for 3-4 d, while being carefully monitored by TLC. The H NMR analysis showed that they have minor differences with shifts at 3.5 and 4.2 ppm, which can be assigned to the diethoxymethyl and the ethoxyl groups of the products.
- Zhang, Dehui,Yuan, Chengye
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supporting information; experimental part
p. 6049 - 6052
(2009/05/30)
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- Synthesis of bispyrrolidines by radical cyclisation of diallylamines using phosphorus hydrides
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Sequential radical addition-cyclisation reactions of diallylamines using either hypophosphorous acid or a bisphosphinothioate are shown to afford bispyrrolidines in good to excellent yields. Georg Thieme Verlag Stuttgart.
- Parsons, Andrew F.,Wright, Anthony
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body text
p. 2142 - 2146
(2009/04/11)
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- PROCESS FOR PREPARATION OF ALKYL PHOSPHINATES
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The invention relates to a new process for the production of alkyl dialkoxyalkylphosphinates. A hypophosphite salt is used in the process.
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(2008/06/13)
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- Preparation of phosphinodipeptide analogs as building blocks for pseudopeptides synthesis
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A simple and effective preparation of phosphinodipeptides, in good overall yields, has been developed. This one pot procedure, allowing the variation of the substituents in α and/or β position to the phosphorus atom and also in α position to the nitrogen atom, consists in the addition of alkyl hypophosphites to imines, followed by Michael-addition on acrylates. To show the value of phosphinodipeptides analogs 1 as synthetic intermediates, selective deprotections of the three functional groups are described.
- Cristau, Henri-Jean,Coulombeau, Agnès,Genevois-Borella, Arielle,Sanchez, Frédéric,Pirat, Jean-Luc
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p. 381 - 391
(2007/10/03)
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- Syntheses and GABA receptor binding properties of 4-amino-1-, 2-, and 3- hydroxybutylphosphinic acids
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Novel racemic 4-amino-1-, 2-, and 3-hydroxybutylphosphinic acids and the corresponding 4-amino-1-, 2-, and 3-hydroxybutyl methylphosphinic acids have been synthesized. The phosphinic acid groups are bioisosteres of the carboxylic acid group, and some of these hydroxy amino acids are GABA(B) antagonists. The novel phosphinic acids were evaluated for their GABA(A) and GABA(B) receptor binding properties using rat brain synaptosomes and were also tested for GABAergic activity in a guinea pig ileum model. None of the phosphinic acids tested were found to be active.
- Kehler, Jan,Ebert, Bjarke,Dahl, Otto,Krogsgaard-Larsen, Povl
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p. 771 - 780
(2007/10/03)
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- Phosphinic acid analogues of GABA. 2. Selective, orally active GABA(B) antagonists
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In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al. described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.
- Froestl,Mickel,Von Sprecher,Diel,Hall,Maier,Strub,Melillo,Baumann,Bernasconi,Gentsch,Hauser,Jaekel,Karlsson,Klebs,Maitre,Marescaux,Pozza,Schmutz,et al.
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p. 3313 - 3331
(2007/10/02)
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- Process for the manufacture of aliphatylphosphinic acid derivatives
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A process for the production of aliphatylphosphinic acid derivatives, especially of alkyl dialkoxyalkylphosphinates having the formula I STR1 in which R is C1 -C4 -alkyl and R' is hydrogen or C1 -C4 -alkyl, comprising reacting, in the presence of an acidic catalyst, aqueous phosphonic acid with the corresponding trialkyl orthoester having the formula II: in whicih R and R' have their previous significances, the amount of the orthoester of formula II used being equal to, or in excess of the stoichiometric amount of both water and phosphinic acid present in the aqueous phosphinic acid reactant.
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- Organophosphorus Intermediates. VI. The Acid-Catalysed Reaction of Trialkyl Orthoformates with Phosphinic Acid
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Trialkyl orthoformates react with phosphinic acid to give the corresponding alkyl phosphinate and alkyl mono- or bis-(dialkoxymethyl)phosphinates; dialkyl phosphonites and phosphine, PH3, are also formed.The formation of P-alkylated products is acid-catalysed and is believed to proceed by alkylation of the trivalent tautomer of phosphinic acid (or its ester) by the dialkoxymethyl carbonium ion arising from the ortho ester in the presence of acid.A comparison with the corresponding reactions of phosphonic acid suggests that the trivalent tautomer of phosphinic acid is formed much more readily than the trivalent form of phosphonic acid and this is accounted for by proposing that the equilibria RPH(O)OR' + H+ RP+H(OH)OR' RP(OH)OR' + H+ (R=H,OH; R'= H, alkyl) lie further to the right for R=H than for R=OH because of inductive effects. 31P and 1H n.m.r. data are reported
- Gallagher, Michael J.,Honegger, Herbert
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p. 287 - 294
(2007/10/02)
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