- Selective Substitution of POCl 3 with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates
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The selectivity of the substitution reaction of phosphoryl chloride with organometallic reagents was investigated using NMR spectroscopy. This led to the discovery that the selectivity of the substitution reaction can be tuned by choosing a proper organometallic reagent. A phosphinate could be obtained by using a Grignard reagent whereas an organozinc reagent provided a phosphonate. Based on these results, one-pot synthetic methods for the preparation of phosphinates and phosphonates using commercially available starting materials were developed. Both methods allow the synthesis of a broad range of either phosphinate or phosphonate derivatives in a straightforward and general procedure. Moreover, using these one-pot procedures, mixed systems substituted with different alkyl/aryl groups can be prepared.
- Verbelen, Bram,Dehaen, Wim,Binnemans, Koen
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p. 2019 - 2026
(2018/04/14)
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- Inhibition of human gastric and pancreatic lipases by chiral alkylphosphonates. A kinetic study with 1,2-didecanoyl-sn-glycerol monolayer
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Enantiomerically pure alkylphosphonate compounds RR'P(O)PNP (R=C(n)H(2n+1), R'=OY with Y=C(n')H(2n'+1) with n=n' or n≠n'; PNP=p-nitrophenoxy) noted (RY), mimicking the transition state occurring during the carboxyester hydrolysis were synthesized and investigated as potential inhibitors of human gastric lipase (HGL) and human pancreatic lipase (HPL). The inhibitory properties of each enantiomer have been tested with the monomolecular films technique in addition to an enyzme linked immunosorbent assay (ELISA) in order to estimate simultaneously the residual enzymatic activity as well as the interfacial lipase binding. With both lipases, no obvious correlation between the inhibitor molar fraction (α50) leading to half inhibition, and the chain length, R or Y was observed. (R11Y16)s were the best inhibitor of HPL and (R10Y11)s were the best inhibitors of HGL. We observed a highly enantioselective discrimination, both with the pure enantiomeric alkylphosphonate inhibitors as well as a scalemic mixture. We also showed, for the first time, that this enantioselective recognition can occur either during the catalytic step or during the initial interfacial adsorption step of the lipases. These experimental results were analyzed with two kinetic models of covalent as well as pseudo-competitive inhibition of lipolytic enzymes by two enantiomeric inhibitors. Copyright (C) 1999 Elsevier Science Ireland Ltd.
- Cavalier, Jean-Francois,Ransac, Stephane,Verger, Robert,Buono, Gerard
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- STEREOSPECIFIC INTRAMOLECULAR CYCLIZATION FOR ASYMMETRIC SYNTHESIS OF (Rp)- AND (Sp)-ENANTIOMERS OF 2-OCTYL- AND 2-PHENYL-4H-1,3,2-BENZODIOXAPHOSPHORIN 2-OXIDES
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Our earlier studies established that: 1) 2-octyl- and 2-phenyl-4H-1,3,2-benzodioxaphosphorin 2-oxides (octyl- and phenyl-BDPOs) induce delayed neuropathy in adult hens at 3 and 200 mg/kg, respectively; 2) phenyl-BDPO also significantly potentiates the acute toxicity of the insecticide malathion to mice; 3) the (Rp) and (Sp) enantiomers of these compounds, resolved on a mg scale by chiral HPLC, differ in potency by 92- and 137-fold, respectively, as inhibitors of neuropathy target esterase.In order to further study the stereospecificity in their toxic effects, the individual enantiomers of octyl- and phenyl-BDPOs are prepared here be a general method of asymmetric synthesis from the corresponding TLC-resolved diastereomeric precursors (Rp)- and (Sp)-methyl N- L-prolinates through acid-catalyzed intramolecular cyclization.This occurs under mild conditions in high yields and involves inversion of configuration at phosphorus.HPLC with the CHIRALCEL OC column established their absolute configurations, based on a previously-published assignment, and 97-100percent e.e. for (Rp)- and (Sp)-octyl- and phenyl-BDPOs. Key words: Asymmetric synthesis, 1,3,2-benzodioxaphosphorin 2-oxide, cyclization, NTE inhibitors, L-propinates, stereochemistry.
- Wu, Shao-Yong,Casida, John E.
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p. 177 - 184
(2007/10/02)
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- STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XXXI. ALKALINE HYDROLYSIS OF 2-ALKYL-2-OXO-1,3,2-DIOXAPHOSPHORINANE AND -PHOSPHEPANE
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Alkaline hydrolysis of 2-alkyl-2-oxo-1,3,2-dioxaphosphorinane and phosphepane was studied in aqueous dioxane.The rate constants were determined at various temperature and the activation parameter of the reaction were evaluated.The hydrolytic process is classified as a AE reaction.Quantitative structure-reactivity relationship was examined by multiple regression analysis involving the rate constants and the structural parameters of the exocyclic substituents on phosphorus.The difference between the hydrolytic behaviour of cyclic alkylphosphonates and carboxylates was also discussed.
- Yuan, Chengye,Li, Shusen,Liao, Xiugao
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p. 205 - 212
(2007/10/02)
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- Process for the preparation of phosphonic acid dihalides
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Process for preparing phosphonic acid dihalides of the formula EQU1 wherein R is alkyl of 1 to 18 carbon atoms, cycloalkyl of 4 to 8 carbon atoms, alkenyl of 2 to 18 carbon atoms, phenyl, phenalkyl or alkyl-phenyl of 7 to 8 carbon atoms, phenyl, phenalkyl or alkyl-phenyl of 7 to 8 carbon atoms, all radicals R optionally being substituted by chlorine, bromine, cyano or lower acyloxy, and wherein X is halogen such as 2-chloroethane phosphonic acid dichloride, by reacting phosphonic or thio-phosphonic acids of the formula EQU2 wherein Y is oxygen or sulfur, their salts or functional derivatives, with acid halides of the formula wherein X is chlorine or bromine and n is 1 or 2, in the presence of 0.2 - 5% or in the presence of 0.01 to 0.2% by weight of 1. compounds containing at least one tri- to pentavalent nitrogen or phosphorus atom, which in the case of nitrogen is bound with 1 to 4, in the case of phosphorus with at least 3 valences to organic radicals having up to 20 carbon atoms, two of these valences optionally forming a double bond, or 2. mono-di- or tribasic organic or inorganic fully amidated acids or tri- or pentavalent phosphorus, the N atom of which optionally being substituted by aliphatic radicals having up to 20 carbon atoms, and the organic radicals of which contain up to 20 carbon atoms, If required, in the presence of an inert solvent.
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