title: Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed Acylation Utilizing Advanced NMR Techniques.
abstract: We report on a detailed NMR spectroscopic study of the catalyst-substrate interaction of a highly enantioselective oligopeptide catalyst that is used for the kinetic resolution of trans-cycloalkane-1,2-diols via monoacylation. The extraordinary selectivity has been rationalized by molecular dynamics as well as density functional theory (DFT) computations. Herein we describe the conformational analysis of the organocatalyst studied by a combination of nuclear Overhauser effect (NOE) and residual dipolar coupling (RDC)-based methods that resulted in an ensemble of four final conformers. To corroborate the proposed mechanism, we also investigated the catalyst in mixtures with both trans-cyclohexane-1,2-diol enantiomers separately, using advanced NMR methods such as T1relaxation time and diffusion-ordered spectroscopy (DOSY) measurements to probe molecular aggregation. We determined intramolecular distance changes within the catalyst after diol addition from quantitative NOE data. Finally, we developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to directly observe intermolecular NOE contacts between the trans-1,2-diol and the cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional spectra. All experimental NMR data support the results proposed by earlier computations including the proposed key role of dispersion interaction.
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.|On leave from Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague, Czech Republic.
authors.forename: Eliška
authors.initials: E
authors.lastname: Procházková
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kolmer
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Ilgen
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Mira
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Lukas
authors.identifier: 0000-0002-3530-8000
authors.initials: L
authors.lastname: Kaltschnee
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Maic
authors.initials: M
authors.lastname: Fredersdorf
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Volker
authors.identifier: 0000-0002-7195-312X
authors.initials: V
authors.lastname: Schmidts
authors.affiliation: Institut für Organische Chemie, Justus-Liebig-Universität, Heinrich-Buff-Ring 17, 35392, Giessen, Germany.
authors.forename: Raffael C
authors.identifier: 0000-0002-2242-4723
authors.initials: RC
authors.lastname: Wende
authors.affiliation: Institut für Organische Chemie, Justus-Liebig-Universität, Heinrich-Buff-Ring 17, 35392, Giessen, Germany.
authors.forename: Peter R
authors.identifier: 0000-0002-3608-5515
authors.initials: PR
authors.lastname: Schreiner
authors.affiliation: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors.forename: Christina M
authors.identifier: 0000-0001-7876-536X
authors.initials: CM
authors.lastname: Thiele
keywords: NMR spectroscopy; RDCs; conformational analysis; enantioselective acylations; pure shift NMR