1932-60-1

Usage

InChI:InChI=1/C7H15O3P/c1-11(8,9)10-7-5-3-2-4-6-7/h7H,2-6H2,1H3,(H,8,9)

Upstream product

• 676-97-1 methylphosphonic acid dichloroanhydride 
• 108-93-0 cyclohexanol 
• 1932-59-8 Methanphosphonsaeure-anhydrid 
• 329-99-7 GF 
• 199116-11-5 C₁₀H₂₃O₃PSi 
• 993-13-5 methylphosphonic acid 
• 175352-88-2 Phosphorous acid cyclohexyl ester dimethyl ester 
• 7040-52-0 cyclohexyl methyl methylphosphonate 
• 7284-56-2 cyclohexyl 4-nitrophenyl methylphosphonate 

Downstream Products

• 7040-52-0 cyclohexyl methyl methylphosphonate 

Relevant academic research and scientific papers

Pathways for the Reactions Between Neurotoxic Organophosphorus Compounds and Oximes or Hydroxamic Acids

To obtain mechanistic insight into the recently demonstrated detoxification ability of β-cyclodextrin derivatives containing substituents with oxime or hydroxamic acid residues, analogous glucose derivatives with the same substituents were treated with cyclosarin (GF), tabun (GA), and O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) in (Tris)-HCl buffer (0.1 m, pH 7.40), and the different reaction pathways were studied by31P NMR spectroscopy and mass spectrometry. Consistent with previous reports, the oxime is phosphonylated by GF, which is followed by elimination of O-cyclohexyl methylphosphonate to afford a nitrile. Reaction of the hydroxamic acid with GA depends on whether the nitrogen atom of the hydroxamic acid bears a substituent or not. The unsubstituted hydroxamic acid affords a stable phosphate ester lacking the cyanide and the dimethylamino group of GA. If the hydroxamic acid is methylated, the initially formed phosphorylated product undergoes a number of transformations, including cleavage of the C–N bond of the hydroxamic acid. Reaction of the hydroxamic acid with VX involves a Lossen rearrangement. These investigations thus show that all investigated nucleophiles are irreversibly modified upon reaction with nerve agents under the chosen conditions, which indicates that cyclodextrins with oximes or hydroxamic acid as substituents are unlikely to afford catalytic nerve-agent scavengers.

Molecular engineering of organophosphate hydrolysis activity from a weak promiscuous lactonase template

Rapid evolution of enzymes provides unique molecular insights into the remarkable adaptability of proteins and helps to elucidate the relationship between amino acid sequence, structure, and function. We interrogated the evolution of the phosphotriesteras

Enzymes for the homeland defense: Optimizing phosphotriesterase for the hydrolysis of organophosphate nerve agents

Phosphotriesterase (PTE) from soil bacteria is known for its ability to catalyze the detoxification of organophosphate pesticides and chemical warfare agents. Most of the organophosphate chemical warfare agents are a mixture of two stereoisomers at the phosphorus center, and the SP-enantiomers are significantly more toxic than the RP-enantiomers. In previous investigations, PTE variants were created through the manipulation of the substrate binding pockets and these mutants were shown to have greater catalytic activities for the detoxification of the more toxic SP-enantiomers of nerve agent analogues for GB, GD, GF, VX, and VR than the less toxic R P-enantiomers. In this investigation, alternate strategies were employed to discover additional PTE variants with significant improvements in catalytic activities relative to that of the wild-type enzyme. Screening and selection techniques were utilized to isolate PTE variants from randomized libraries and site specific modifications. The catalytic activities of these newly identified PTE variants toward the SP-enantiomers of chromophoric analogues of GB, GD, GF, VX, and VR have been improved up to 15000-fold relative to that of the wild-type enzyme. The X-ray crystal structures of the best PTE variants were determined. Characterization of these mutants with the authentic G-type nerve agents has confirmed the expected improvements in catalytic activity against the most toxic enantiomers of GB, GD, and GF. The values of kcat/Km for the H257Y/L303T (YT) mutant for the hydrolysis of GB, GD, and GF were determined to be 2 ×106, 5 ×105, and 8 ×105 M-1 s-1, respectively. The YT mutant is the most proficient enzyme reported thus far for the detoxification of G-type nerve agents. These results support a combinatorial strategy of rational design and directed evolution as a powerful tool for the discovery of more efficient enzymes for the detoxification of organophosphate nerve agents.

Alkyl methylphosphonic acids, the degradation products of organophosphorous CWA - preparation and direct quantitative GC-FID analysis

Seven alkyl methylphosphonic acids, products of hydrolytic degradation of organophosphorus chemical warfare agents, were obtained with a high purity (mostly above 98%), with the aim of being applyed as future certified reference materials. Ethyl (EMPA), i

Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design

Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

Synthesis of alkyl- and arylphosphonic acid monoesters by direct esterification of dibasic phosphonic acids in the presence of an arsonic acid catalyst

Partial hydrolysis of a diester, hydrolysis of the monochloro monoester, or alcoholysis of a phosphonic acid anhydride generally is used to prepare monoesters of alkyl- and arylphosphonic acids. Limited cases have been reported for the esterification of a dibasic phosphonic acid to yield the monoester, and none of these methods are as simple as the analogous method for preparing carboxylic acid esters, in which the carboxylic acid is esterified with an alcohol in the presence of an acid catalyst. Described is a method for preparing monoesters of alkyl- and arylphosphonic acids by direct esterification with an alcohol in the presence of a catalytic amount of phenylarsonic acid. The water formed during the reaction is removed azeotropically. For example, methylphosphonic acid was esterified in good yield to give its isopropyl, butyl, cyclohexyl, bornyl, and octadecyl monoesters. Similarly prepared are the ethyl, butyl, hexyl, and 2-(ethylthio)ethyl monoesters of phenylphosphonic acid, as well as 2-isopropoxyethyl hydrogen ethylphosphonate and 2-methoxyethyl hydrogen benzylphosphonate.

Preparation, derivatization with trimethylsilyldiazomethane, and GC/MS analysis of a "pool" of alkyl methylphosphonic acids for use as qualitative standards in support of counterterrorism and the chemical weapons convention

There are hundreds of nerve agents in the class of alkyl methylphosphonofluoridates covered by Schedule 1 of the CWC (Chemical Weapons Convention). Hydrolysis of these sarin-like nerve agents results in an equal number of alkyl methylphosphonic acids. These alkyl methylphosphonic acids are persistent and provide good evidence of specific agent production or use. In order to support the CWC and counterterrorism activities, it is desirable to have ready access to each of these hydrolysis products for use as qualitative standards. A means for simultaneously producing multiple alkyl methylphosphonates from methylphosphonic acid and the corresponding alcohols was developed. Derivatization of these alkyl methylphosphonic acids with trimethylsilyldiazomethane yields the corresponding methyl esters which are suitable for GC/MS analysis.

Solid-phase synthesis of some alkyl hydrogen methylphosphonates

Eleven alkyl hydrogen methylphosphonates of structure RO(HO) P(O)Me were made by phosphoramidite chemistry on hydroxymethyl polystyrene resin; R = Me, Et, n-Pr, i-Pr, n-Bu, n-hexyl, n-octyl, cyclohexyl, cycloheptyl, cyclooctyl, and 3,3-dimethylbutan-2-yl

Organophosphorus chemistry. Part 1: The synthesis of alkyl methylphosphonic acids

Several alkyl hydrogen methylphosphonates of structure RO(HO)P(O)Me were synthesised by a three-stage route [R =i-Pr, n-Bu, i-Bu, s-Bu, pinacolyl Me3C-CH(Me)-, cyclopentyl and cyclohexyl]. Trimethyl phosphite was transesterified with alcohols in the presence of sodium catalyst to give the mixed phosphites (MeO)2POR in 6-64% yield. Treatment of these with methyl iodide gave alkyl methyl methylphosphonates RO(MeO)P(O)Me in 66-95% yield. Selective demethylation of these compounds by bromotrimethylsilane, followed by methanolysis of the phosphorus silyl esters RO(Me3SiO)P(O)Me, gave the hydrogen phosphonates in 60-97% yield.

Synthesis of alkyl hydrogen alkylphosphonates

The synthesis of alkyl hydrogen alkylphosphonates 1 was studied. Different synthetic routes were investigated and it was found that alkylphosphonic anhydrides can serve as ideal precursors for the synthesis of those half-acids. It was also shown that isopropyl phosphonic dichloride reacts in a unique fashion to produce alkyl hydrogen isopropylphosphonates in moderate yields.