676460-36-9Relevant academic research and scientific papers
Monofluoroalkene-Isostere as a 19F NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3
Drouin, Myriam,Wadhwani, Parvesh,Grage, Stephan L.,Bürck, Jochen,Reichert, Johannes,Tremblay, Sébastien,Mayer, Marie Sabine,Diel, Christian,Staub, Alexander,Paquin, Jean-Fran?ois,Ulrich, Anne S.
, p. 1511 - 1517 (2020/02/05)
Solid-state 19F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the 19F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)3 are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for 19F NMR structure analysis.
Diastereoselective synthesis of highly functionalized fluoroalkene dipeptide isosteres and its application to Fmoc-based solid-phase synthesis of a cyclic pentapeptide mimetic
Narumi, Tetsuo,Tomita, Kenji,Inokuchi, Eriko,Kobayashi, Kazuya,Oishi, Shinya,Ohno, Hiroaki,Fujii, Nobutaka
, p. 4332 - 4346 (2008/09/20)
A diastereoselective and divergent method for synthesis of a highly functionalized (Z)-fluoroalkene dipeptide isosteres has been developed. The key feature of this synthetic method is an efficient one-pot reaction involving reduction/asymmetric alkylation
SmI2-Mediated Reduction of γ,γ-Difluoro-α ,β-enoates with Application to the Synthesis of Functionalized (Z)-Fluoroalkene-Type Dipeptide Isosteres
Otaka, Akira,Watanabe, Junko,Yukimasa, Akira,Sasaki, Yoshikazu,Watanabe, Hideaki,Kinoshita, Takayoshi,Oishi, Shinya,Tamamura, Hirokazu,Fujii, Nobutaka
, p. 1634 - 1645 (2007/10/03)
A samarium diiodide (SmI2)-mediated reduction of γ,γ-difluoro-α,β-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the γ,γ-difluoro-α,β-enoates by SmI2 proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to α-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI2-HCHO reagent system with chiral enoate 34 provided D-Phe-ψ [(Z)-CF=CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the α-position. This was achieved by a sequence of manipulations consisting of β-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of α,α-difluoro-β-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.
