359-06-8Relevant articles and documents
Jenkins,Ladd
, p. 1237 (1968)
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.
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.
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.
