135789-87-6

Upstream product

• 56069-39-7 diethyl phenylsulfonylmethylphosphonate 
• 20808-12-2 fluoromethyl phenyl sulfone 
• 814-49-3 diethyl chlorophosphate 
• 3112-85-4 methylphenylsulfonate 
• 38066-16-9 diethyl [(phenylthio)methyl]phosphonate 

Downstream Products

• 114969-03-8 (1-fluoroethenyl)phenylsulfane dioxide 
• 114969-23-2 1-((Z)-2-Benzenesulfonyl-2-fluoro-vinyl)-4-nitro-benzene 
• 114969-22-1 1-(2-benzenesulfonyl-2-fluoro-vinyl)-4-nitrobenzene 
• 114969-14-1 (E)-1-(2-fluoro-2-(phenylsulfonyl)vinyl)-4-methoxybenzene 
• 114969-21-0 (Z)-1-fluoro-1-phenylsulfonyl-pent-1-ene 
• 114969-20-9 (E)-1-fluoro-1-phenylsulfonyl-pent-1-ene 
• 114969-10-7 (1-Benzenesulfonyl-1-fluoro-but-3-enyl)-phosphonic acid diethyl ester 
• 174075-36-6 (Z)-2-(2-phenylethyl)-1-fluoro-1-(phenylsulfonyl)ethene 
• 98506-80-0 1,1-diphenyl-2-(phenylsulfonyl)-2-fluoroethylene 
• 352438-93-8 α⁴,3-O-isopropylidene-α⁵-deoxy-α⁵-[diethyl(1'-fluoro-1'-phenylsulfonyl)phosphonomethyl]pyridoxine 
• 352438-95-0 benzyl 6-deoxy-6-diethyl-(1'-fluoro-1'-phenylsulfonyl)phosphonomethyl-2,3,4-tri-O-benzyl-β-D-glucopyranoside 
• 718615-59-9 (Z)-6-chloro-1-fluoro-2-methyl-1-(phenylsulfonyl)-1-hexene 
• 147920-46-5 1-fluoro-2-phenyl-1-(phenylsulfonyl)ethene 
• 874757-75-2 1-fluoro-2-phenyl-1-(phenylsulfonyl)-1-propene 

Relevant academic research and scientific papers

Straightforward and scalable synthesis of diethyl fluoro(phenylsulfonyl)methylphosphonate

A process is described for the synthesis of diethyl fluoro(phenylsulfonyl)methylphosphonate which is easily and safely performed on a multi-kilogram scale.

Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure-Activity Relationship, Inhibition Mechanism, Metabolism, and in Vivo Studies

Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 μM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.

Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors

We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones.

Organocatalytic alkynylation of densely functionalized monofluorinated derivatives: C(sp3)-C(sp) coupling

Organocatalytic alkynylation of nucleophilic fluorocarbons using hypervalent iodine compounds under cinchona-based catalysis, namely using O-allyl N-anthracenyl cinchona alkaloid derivative II, is described. The reaction gives the final fluoro-propargyl compounds in good to excellent yields (up to 91%) and with moderate to low enantioselectivity (up to 61% ee). The reaction represents the first example of the use of hypervalent iodine compounds for the construction of fluorinated compounds and opens access to the preparation of biologically attractive compounds such as 1,2,3-triazoles.

Regioselective anodic fluorination of α-(arylthio)benzylphosphonate esters, α-(arylthio)methylphosphonate esters and their analogues

Regioselective anodic α-fluorination of α-(arylthio) benzylphosphonate esters and [(arylthio)methyl]- and [(heteroarylthio)methyl] phosphonate esters was successfully carried out at a glassy carbon anode or platinum anode in dimethoxyethane and nitrometha

Synthesis of the multisubstituted halogenated olefins via cross-coupling of dihaloalkenes with alkylzinc bromides

The 1-fluoro-1-haloalkenes undergo Pd-catalyzed Negishi cross-couplings with primary alkylzinc bromides to give multisubstituted fluoroalkenes. The alkylation was trans-selective giving pure Z-fluoroalkenes in most cases. The highest yields were obtained with Pd2(dba)3 and PdCl 2(dppb) catalysts but the best stereochemical outcome was obtained with less reactive Pd(PPh3)4. The tertiary alkylzincs also produced desired fluoroalkenes in high yields. Coupling of β,β- dichlorostyrene with organozinc reagent resulted in the formation of monocoupled product.

Radical-mediated silyl- and germyldesulfonylation of vinyl and (α-fluoro)vinyl sulfones: Application of tris(trimethylsilyl)silanes and tris(trimethylsilyl)germanes in Pd-catalyzed couplings

Equation presented. Radical-mediated silyl- and germyldesulfonylations of various vinyl and (α-fluoro)vinyl sulfones with tris(trimethylsilyl)silane and germanium hydrides provide access to vinyl and (α-fluoro)vinyl silanes and germanes. Upon oxidative treatment with hydrogen peroxide in basic aqueous solution, the vinyl tris(trimethylsilyl)silanes and -germanes undergo Pd-catalyzed cross-couplings with aryl halides.

New Polyfluorinated Organotin Reagents. Stereoselective Synthesis of (Z)-α-Fluoro-β-trifluoromethylvinylstannanes

(Formula Presented) A new methodology for the synthesis of (Z)-α-fluoro-β-trifluoromethylvinylstannanes, which are useful polyfluorinated organotin reagents for the synthesis of fluorine-containing biologically active compounds, is described.

Method of treating a neoplastic disease state by conjunctive therapy with 2'-fluoromethylidene derivatives and radiation or chemotherapy

The present invention relates to a method of treating a patient afflicted with a neoplastic disease state comprising the administration thereto of an effective antineoplastic amount of ionizing or nonionizing radiation, or an effective antineoplastic amount of a DNA-reactive chemotherapeutic agent in conjunctive therapy with an effective sensitizing amount of a compound of formula (I).

Process for the preparation of ribonucleotide reductase inhibitors

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors. The novel process of the present invention utilizes a cytidine derivative as the required starting material and provides the ribonucleotide reductase inhibitor in a more efficient five step reaction sequence. The present invention further provides the ribonucleotide reductase inhibitor in a four step reaction sequence and results in an overall yield of greater than 35%.