Foldamer‐Mediated Remote Stereocontrol: >1,60 Asymmetric Induction

Abstract

An N-terminal L-α-methylvaline dimer induces complete conformational control over the screw sense of an otherwise achiral helical peptide foldamer formed from the achiral quaternary amino acids Aib and Ac6 c. The persistent right-handed screw-sense preference of the helix enables remote reactive sites to fall under the influence of the terminal chiral residues, and permits diastereoselective reactions such as alkene hydrogenation or iminium ion addition to take place with 1,16-, 1,31-, 1,46- and even 1,61-asymmetric induction. Stereochemical information may be communicated in this way over distances of up to 4 nm.

Screw sense alone can govern enantioselective extension of a helical peptide by kinetic resolution of a racemic amino acid

“…33,34 The induced screw-sense preference can be quantified using 1 H, 19 (CD) techniques, and exploited in the remote induction of asymmetry at a new stereogenic centre up to 60 bonds from the source of screw-sense induction. 37 This ability to induce a quantifiable screw-sense preference in an Aib oligomer forms the foundation of the study we now describe. Initial studies made use of the racemic pentapeptide (±)-AcPheAib4OH 1a, evaluating the diastereoselectivity of its coupling reactions by NMR (Table 1).…”

Real‐Time Band‐Selective Homonuclear Proton Decoupling for Improving Sensitivity and Resolution in Phase‐Sensitive J‐Resolved Spectroscopy

“…In particular,the real-time band-selectivehomonuclear (BASH)d ecoupling, although not broadband,i mproves both the resolution as well as the sensitivity of 1D 1 HNMR spectroscopy and in the direct dimensions of various 1 H-detected 2D NMR spectroscopy [27,36,41] in ab and-or spin-selectivem anner. Recently,aband-selective 'pure-shift' selectiver efocusing (SERF)t echnique was proposed to extract 1 H-1 H J coupling between selected 1 Hp airs in overcrowdeds pectral regions.…”

“…[27,36,41].T he nonselective 908 pulse after the z filter in Figure 1A,i sr eplaced by aE Burp-2 shaped 908 pulse marked as Ei nF igure 1B for the selective excitation of the group of resonances in the real-time BASH-decoupled J-resolved experiment.H ollow-shaped pulses marked as rw ere appliedp eriodically during acquisition anda re 1808 ReBurp shaped pulses for refocusing the protons of interest, they were followed by an onselective 1808 pulse to invert all spins. As ar esult, the protons of interestw ere selectively decoupled from the rest, while allowing their chemical-shift evolution to continue during acquisition.…”

“…[27,36,41] The proton-proton decoupling is achieved by repeated application of ab and-selective and an onselective 1808 pulse pair during interrupted acquisition. Peptides and proteins are suitable for the BASH/HOBS method as they offer the unique opportunity forb and-selective refocusing of amide protons ( 1 H N )o ra lpha protons ( 1 H a ).…”

Signal transduction in oligoamide foldamers by selective non-covalent binding of chiral phosphates at a urea binding site

“…Provided there is no direct interaction between the N terminus of the foldamer and the labelled Aib, their chemical shift difference (anisochronicity) will be proportional to the helical excess induced in the foldamer. [52][53][54] These urea-capped foldamers were only sparingly soluble in acetonitrile and in tetrahydrofuran. Each foldamer was mixed with a three-fold excess of the phosphoric acid 2a ( Fig.…”