359-06-8Relevant academic research and scientific papers
Synthesis of some new N-monosubstituted fluoroacetamides
Miscevic, S.,Minic, D.,Petrovic, S.
, p. 239 - 247 (1992)
Twenty new N-monosubstituted fluoroacetamides with potential toxicological properties have been synthesized by acylation of the corresponding amines with fluoroacetyl chloride.The substituents were cycloalkyl or various alkyl (with straight or branched carbon chain) groups.The yields ranged from 50 to 92percent.
Ester Enolate Claisen Rearrangements of Allyl α-Fluoroacetates and α-Fluoropropanoates
Welch, John T.,Plummer, Janet S.,Chou, Tso-Sheng
, p. 353 - 359 (1991)
The ester enolate Claisen rearrangement of allyl α-fluoroacetates 1 forms 2-fluoroalkenoic acids 2 in good to excellent yield with good internal asymmetric induction.This selectivity was unexpected as stereoselective deprotonation of fluoroacetates is not normally possible.The selective formation of the required α-fluoro silyl ketene acetal 3 was found to result from the stereoselective rearrangement of the allyl α-fluoro-α-silylacetate isomer.Although silyl ketene acetals derived from α-fluoropropanoates 7 also rearranged, control of internal asymmetric induction was not possible.
Development of Benzenesulfonamide Derivatives as Potent Glutathione Transferase Omega-1 Inhibitors
Xie, Yiyue,Tummala, Padmaja,Oakley, Aaron J.,Deora, Girdhar Singh,Nakano, Yuji,Rooke, Melissa,Cuellar, Matthew E.,Strasser, Jessica M.,Dahlin, Jayme L.,Walters, Michael A.,Casarotto, Marco G.,Board, Philip G.,Baell, Jonathan B.
, p. 2894 - 2914 (2020/04/08)
Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1β and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhibitors that act by covalent labeling. In this study, structure-activity relationship (SAR) elaboration of the reported GSTO1-1 inhibitor C1-27 was undertaken. Compounds were evaluated for inhibitory activity toward purified recombinant GSTO1-1 and for indicators of target engagement in cell-based assays. As covalent inhibitors, the kinact/KI values of selected compounds were determined, as well as in vivo pharmacokinetics analysis. Cocrystal structures of key novel compounds in complex with GSTO1-1 were also solved. This study represents the first application of a biochemical assay for GSTO1-1 to determine kinact/KI values for tested inhibitors and the most extensive set of cell-based data for a GSTO1-1 inhibitor SAR series reported to date. Our research culminated in the discovery of 25, which we propose as the preferred biochemical tool to interrogate cellular responses to GSTO1-1 inhibition.
Hapten design and monoclonal antibody to fluoroacetamide, a small and highly toxic chemical
Yang, Ling,Zhang, Xiya,Shen, Dongshuai,Yu, Xuezhi,Li, Yuan,Wen, Kai,Shen, Jianzhong,Wang, Zhanhui
, p. 1 - 12 (2020/07/08)
Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment. However, achieving this goal is a great challenge, mainly due to the very low molecular weight of FAM. Here, we design two groups of FAM haptens for the first time, maximally exposing the fluorine or amino groups, with the aid of linear aliphatic or phenyl-contained spacer arms. Interestingly, whereas the hapten with fluorine at the far end of the hapten did not induce an antibody response to FAM, the hapten with an amino group at the far end and phenyl-contained spacer arm triggered a significantly specific antibody response. Finally, a monoclonal antibody (mAb) named 5D11 was successfully obtained with an IC50 value of 97 μg mL?1 and negligible cross-reactivities to the other nine functional and structural analogs.
Self-Disproportionation of Enantiomers (SDE) via achiral gravity-driven column chromatography of N-fluoroacyl-1-phenylethylamines
Wzorek, Alicja,Kamizela, Angelika,Sato, Azusa,Soloshonok, Vadim A.
, p. 37 - 43 (2017/04/14)
The study of the self-disproportionation of enantiomers (SDE) via gravity-driven achiral column chromatography of a series of N-fluoroacetylated amides derived from 1-phenylethylamine is described. The chromatographic experiments performed with N-fluoroacetylated amides confirmed, that the process of molecular association in solution leading to the SDE manifestation, is sensitive to the fluorine content and type of solvent used. Thus, the two opposite eluting profiles for the same compound were observed in two different eluents. Moreover, the amides bearing perfluoroalkyl groups showed opposite eluting order as compared to the established profile for fluorine-free N-acetyl-1-phenylethylamine.
Synthetic routes towards fluorine-containing amino sugars: Synthesis of fluorinated analogues of tomosamine and 4-amino-4-deoxyarabinose
Albler, Christopher,Schmid, Walther
, p. 2451 - 2459 (2014/05/06)
Fluorinated analogues of bioactive amino sugars are of high interest in medicinal chemistry. We developed a straightforward synthetic route towards this class of carbohydrates by applying a titanium-mediated aldol addition. Thus, two-carbon chain elongations of serine- and threonine-derived aldehydes with a chiral fluoroacetyl-oxazolidinone could be achieved in good yields and excellent diastereoselectivities to generate a fluorohydrin-containing carbon skeleton. A short deprotection sequence subsequently furnished the pyranoid forms of various 4-amino-2-fluoropentoses and -hexoses, respectively. The versatility of this strategy was demonstrated by the stereoselective synthesis of naturally abundant 4-amino-4-deoxyarabinose and 4-amino-4,6-dideoxygalactose (tomosamine). 4-Amino-2-fluoropentoses and -hexoses were prepared through two-carbon chain elongations by Ti-mediated aldol additions of serine- and threonine-derived amino aldehydes to fluoroacetyl-ephedrine-oxazolidinone. Excellent stereoselectivities were attained for matched-case fluorohydrins, which were deprotected in a short sequence. Copyright
Conformational preferences for some 2-substituted N-methoxy-N- methylacetamides through spectroscopic and theoretical studies
Olivato, Paulo R.,Da Silva Gomes, Roberto,Rodrigues, Alessandro,Reis, Adriana K.C.A.,Domingues, Nelson L.C.,Rittner, Roberto,Dal Colle, Maurizio
experimental part, p. 106 - 116 (2010/10/04)
The analysis of the IR carbonyl band of the 2-substituted N-methoxy-N-methylacetamides Y-CH2C(O)N(OMe)Me (Y = F 1, OMe 2, OPh 3, Cl 4), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1-4, indicated the existence of cis-gauche conformers i.e. (c) and (g) for 1 and 3, (c1, c2) and (g1, g 2) for 2, and (c) and (g1, g2) for 4. In the gas phase, the g conformer population prevails over the c one, for 1 and 3, the (c1 + c2) population prevails over the (g1 + g2) one for 2, and the (g1 + g2) conformer population is more abundant than (c) one for 4. In n-hexane solution, the cis conformer is more abundant for 1-3. The occurrence of Fermi resonance in the νCO region, in n-hexane, precludes the estimative of relative populations of the (c, g1, g2) conformers for 4. The SCI-PCM calculations agree with the solvent effect on the νCO band component relative intensities for 1-3. NBO analysis showed that the n N → πco* orbital interaction is the main factor which stabilizes the gauche (g, g1, g2) conformers for 1-4 into a larger extent relative to the cis (c, c1, c2) ones. The nY → πco *, σC-Y → πco*, πco → σC-Y* and πco* → σC-Y* orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1-4 is responsible for the occurrence of Yδ-(4)?Oδ-(9) and Y δ-(4)?Nδ-(7) short contacts in the gauche (g, g1, g2) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed stabilization of the gauche (g, g1, g2) and cis (c, c1, c2) conformers, both in the gas phase and in the solution for 1-4. However, the cis conformer predominance, in non polar solvents, for the 2-substituted N-methoxy-N-methyl acetamides 1-3, bearing in α first raw (fluorine and oxygen) atoms, is in the opposite direction to the gauche conformer preference for the corresponding 2-substituted N,N-dialkyl-acetamides.
Lewis acid mediated Peterson fluoroolefination
Welch, John T.,Gregor, Tamas,Kornilov, Andrei
, p. 171 - 178 (2007/10/03)
Peterson olefination of the alkyl and aryl aldehydes with C,O-bis(triethylsilyl)fluoroketene acetal 1 promoted by titanium tetrachloride and dimethylaluminum chloride was investigated. Desired fluoroolefins were formed with high stereoselectivity and moderate to high yields.
FLUOROOLEFIN PEPTIDE ISOSTERES - TOOLS FOR CONTROLLING PEPTIDE CONFORMATIONS
Boros, Livia G.,Corte, Bart De,Gimi, Rayomand H.,Welch, John T.,Wu, Yang,Handschumacher, Robert E.
, p. 6033 - 6036 (2007/10/02)
Fluoroolefin dipeptide isosteres were synthesized applying the Peterson reaction as a novel method for fluoroolefination.The dipeptide isosteres were elaborated to provide the conformationally constrained analogs (1-(R), 1-(S) and 2-(R), 2-(S)) of the Suc-Ala-Gly-Pro-Phe-pNA tetrapeptide, a synthetic substrate of cyclophilin.
Determination of an 8-? interatomic distance in a helical peptide by solid-state NMR spectroscopy
Holl, Susan M.,Marshall, Garland R.,Beusen, Denise D.,Kociolek, Karol,Redlinski, Adam S.,Leplawy, Miroslaw T.,McKay, Robert A.,Vega, Shimon,Schaefer, Jacob
, p. 4830 - 4833 (2007/10/02)
The combination of transferred-echo double resonance (TEDOR) with rotational-echo double resonance (REDOR) has been used to measure an 8-? fluorine-carbon internuclear distance in a nine-residue fragment of the peptide antibiotic emerimicin. The fragment is 19FCH2CO-Phe-MeA-MeA-[1-13C]MeA-[ 15N]Val-Gly-Leu-MeA-MeA-OBzl (MeA = α-methylalanine or aminoisobutyric acid). The TEDOR part of this magic-angle-spinning, solid-state NMR experiment selects the 13C label by its dipolar coupling to 15N and suppresses the natural-abundance carbon background. The REDOR part of the experiment measures dipolar coupling of the selected carbon to 19F. The TEDOR-REDOR combined experiment works with a variety of spin 1/2 nuclei and can be used to characterize internuclear distances and geometry in macromolecular aggregates that do not crystallize.
