133384-81-3

Basic information

• Product Name: dibenzyl 2-fluoroMalonate
• Synonyms: dibenzyl 2-fluoroMalonate
• CAS NO: 133384-81-3
• Molecular Formula: C₁₇H₁₅FO₄
• Molecular Weight: 302.2970032
• Mol File: 133384-81-3.mol

Chemical Properties

• Boiling Point: 399.5±32.0 °C(Predicted)
• Appearance: /
• Density: 1.232±0.06 g/cm3(Predicted)
• PKA: 10.21±0.46(Predicted)
• CAS DataBase Reference: dibenzyl 2-fluoroMalonate(CAS DataBase Reference)
• NIST Chemistry Reference: dibenzyl 2-fluoroMalonate(133384-81-3)
• EPA Substance Registry System: dibenzyl 2-fluoroMalonate(133384-81-3)

Safety Data

• Hazardous Substances Data: 133384-81-3(Hazardous Substances Data)

Upstream product

• 15014-25-2 malonic acid dibenzyl ester 
• 685-88-1 fluoromalonic acid diethyl ester 
• 100-51-6 benzyl alcohol 
• 344-14-9 dimethyl 2-fluoromalonate 

Downstream Products

• 133384-82-4 N-phthalyl-4-fluoro-4-benzyloxycarbonyl-glutamic acid, α-methyl, γ-benzyl diester 

Relevant articles and documents

Peptide-based covalent inhibitors of MALT1 paracaspase

Potent and selective substrate-based covalent inhibitors of MALT1 protease were developed from the tetrapeptide tool compound Z-VRPR-fmk. To improve cell permeability, we replaced one arginine residue. We further optimized a series of tripeptides and identified compounds that were potent in both a GloSensor reporter assay measuring cellular MALT1 protease activity, and an OCI-Ly3 cell proliferation assay. Example compounds showed good overall selectivity towards cysteine proteases, and one compound was selected for further profiling in ABL-DLBCL cells and xenograft efficacy models.

Optimization and anti-cancer properties of fluoromethylketones as covalent inhibitors for ubiquitin C-terminal hydrolase L1

The deubiquitinating enzyme (DUB) UCHL1 is implicated in various disease states including neurodegenerative disease and cancer. However, there is a lack of quality probe molecules to gain a better understanding on UCHL1 biology. To this end a study was carried out to fully characterize and optimize the irreversible covalent UCHL1 inhibitor VAEFMK. Structure-activity relationship studies identified modifications to improve activity versus the target and a full cellular characterization was carried out for the first time with this scaffold. The studies produced a new inhibitor, 34, with an IC50 value of 7.7 μM against UCHL1 and no observable activity versus the closest related DUB UCHL3. The molecule was also capable of selectively inhibiting UCHL1 in cells and did not demonstrate any discernible off-target toxicity. Finally, the molecule was used for initial probe studies to assess the role of UCHL1 role in proliferation of myeloma cells and migration behavior in small cell lung cancer cells making 34 a new tool to be used in the biological evaluation of UCHL1.

METHOD FOR PRODUCING FLUOROMALONIC ESTER DERIVATIVE

PROBLEM TO BE SOLVED: To provide a method for producing a fluoromalonic ester derivative, useful as a raw material of electronic materials and as a synthetic intermediate of an agrochemical, which does not use or waste an expensive fluorinating agent and also has a short process. SOLUTION: A fluoromalonic ester derivative represented by a formula (2) is produced by reacting a malonic ester derivative with the 2-position modified with R3 with N-fluoro-bis(methanesulfonyl)imide in the presence of a Lewis acid. (R1 and R2 are each independently a methyl group, an ethyl group, a C3-4 linear, branched or cyclic alkyl group, a phenyl group, or a benzyl group; and R3 is H, a methyl group or an ethyl group.) SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT

METHOD OF PRODUCING MONOFLUOROMALONIC ACID DERIVATIVE

PROBLEM TO BE SOLVED: To provide a method of producing a monofluoromalonic acid ester derivative that has a high yield, facilitates separation of a product, and allows industrial production. SOLUTION: A malonic acid ester derivative (1) is reacted with a hydrogen fluoride source in the presence of an iodosylbenzene derivative or an iodobenzene derivative and an oxidizing agent, to produce a monofluoromalonic acid derivative (4). COPYRIGHT: (C)2015,JPOandINPIT

A Convenient Synthesis of 2-Fluoro- and 2-Chloromalonic Esters Mediated by Hypervalent Iodine

Direct fluorination of malonic esters with a reagent system of iodosylbenzene and Et3N·5HF gave the corresponding 2-fluoromalonic esters in good to high yields. Direct chlorination using iodosylbenzene and hydrochloric acid also provided the 2-chloromalonates in high yields.

In vitro and ex vivo inhibition of hepatitis a virus 3C proteinase by a peptidyl monofluoromethyl ketone

Hepatitis A virus (HAV) 3C proteinase is the enzyme responsible for the processing of the viral polyprotein. Although a cysteine proteinase, it displays an active site configuration like those of the mammalian serine proteinases (Malcolm, B. A. Protein Science 1995, 4, 1439). A peptidyl monofluoromethyl ketone (peptidyl-FMK) based on the preferred peptide substrates for HAV 3C proteinase was generated by first coupling the precursor, N,N-dimethylglutamine fluoromethylalcohol, to the tripeptide, Ac-Leu-Ala-Ala-OH, and then oxidizing the product to the corresponding peptidyl-FMK( (Ac-LAAQ'-FMK). This molecule was found to be an irreversible inactivator of HAV 3C with a second-order rate constant of 3.3 x 102 M--1 s-1. 19F NMR spectroscopy indicates the displacement of fluoride on inactivation of the enzyme by the fluoromethyl ketone. NMR spectroscopy of the complex between the 13C-labeled inhibitor and the HAV 3C proteinase indicates that an (alkylthio)methyl ketone is formed. Studies of polyprotein processing, using various substrates generated by in vitro transcription/translation, demonstrated efficient blocking of even the most rapid proteolytic events such as cleavage of the 2A-2B and 2C-3A junctions. Subsequent ex vivo studies, to test for antiviral activity, show a 25-fold reduction in progeny virus production as the result of treatment with 5 μM inhibitor 24 h postinfection.

SYNTHESIS OF 5,5'-DIHYDROXYLEUCINE AND 4-FLUORO-5,5'-DIHYDROXYLEUCINE, THE REDUCTION PRODUCTS OF 4-CARBOXYGLUTAMIC AND 4-CARBOXY-4-FLUOROGLUTAMIC ACIDS

Schemes for the synthesis of 5,5'-dihydroxyleucine 3 and its 4-fluoro analog 7 involving the condensation of a suitable 'aminoacid moiety' with 2,2-dimethyl-5-iodomethyl-1,3-dioxane 15D or its fluoro analog 27A were tested.The anion of the ethyl N-diphenylmethylene-glycinate 25 gave better yields of 3 than the classical anion of diethyl acetamidomalonate.This strategy could not be successfully applied to the synthesis of 7, which could be prepared by reduction of a suitably protected 4-fluoro-4-carboxyglutamate with BMS.