Chiral Molecular Recognition in a Tripeptide Benzylviologen Cyclophane Host

Abstract

A cationic chiral cyclophane was synthesized and studied as a host for chiral and racemic π-donor molecules. The cyclophane host has a rigid binding cavity flanked by (S)-(valine-leucine-alanine) and N,N′-dibenzyl-4,4′-bipyridinium subunits, which allow for hydrogen-bonding and π-stacking interactions with included aromatic guest molecules. 1 H NMR binding titrations were performed with several different pharmaceutically interesting guest molecules including β-blockers, NSAIDs, and amino acids and amino acid derivatives. The host-guest complexation constants were generally small for neutral and cationic guests (0-39 M -1 at 20 °C in water/acetone mixtures). However, a (R)/(S) enantioselectivity ratio of 13 ( 5 was found for DOPA, a strongly π-donating cationic guest. Two-dimensional NOESY 1 H NMR spectra confirm that (R)-DOPA binds inside the cavity of the host and that there is no measurable interaction of the cavity with (S)-DOPA under the same conditions.

Activity-based probes for protein tyrosine phosphatases

“…The chemical synthesis of PTP probes I and II involved synthesizing a common intermediate, compound 10, in a seven-step procedure (Scheme 1) and its subsequent coupling with the (ϩ)biotinamido-N-hydroxysuccinimide ester analogues, followed by the deprotection of the phosphonate diethyl ester (Scheme 2). Thus, 4-cyanobenzyl bromide 3 was hydrolyzed in the presence of barium carbonate to produce 4-cyanobenzyl alcohol 4, which was subsequently reduced with lithium aluminum hydride under strict argon atmosphere to yield 4-hydroxymethyl-benzyl-ammonium chloride 5, upon acidic aqueous extraction (17). The amine functionality of 4-hydroxymethyl-benzyl-ammonium chloride 5 was then first masked by tert-butyl carbamate to render (4-hydroxymethylbenzyl)carbamic acid tert-butyl ester 6 (18).…”

Enantiomeric discrimination of leucine enantiomers by nanotubular cyclic peptides: DFT and ONIOM calculation of the absorption spectra of guested enantiomers

“…There are various experimental [6][7][8] and theoretical [9][10][11][12] studies dedicated to examine different aspects of this phenomenon. The cyclic peptides are used as excellent host in host-guest chemistry because they could form inclusion complexes with guest molecules [13][14][15][16][17][18][19][20][21][22][23][24].…”

Chiral Heterocycle-Based Receptors for Enantioselective Recognition

“…Mallouk et al [65] have synthesized the(S)-valine-leucine-alanine cyclophane, 26 (Scheme 3). The bipyridine fragment, 23 of 26 was prepared by the reaction of 4, 4'-bipyridine with 4-(chloromethyl)benzoic acid followed by the treatment with 4-(bromomethyl)benzylamine hydrobromide.…”

“…This result unambiguously confirmed a strong and enantioselective binding of (R)-DOPA inside the cavity of 26, while no measurable interaction was detected for (S)-DOPA under the same conditions. Mallouk et al [65] have synthesized the(S)-valine-leucine-alanine cyclophane, 26 (Scheme 3). The bipyridine fragment, 23 of 26 was prepared by the reaction of 4, 4'-bipyridine with 4-(chloromethyl)benzoic acid followed by the treatment with 4-(bromomethyl)benzylamine hydrobromide.…”