New Artificial Host Compounds Containing Galactose End Groups for Binding Chiral Organic Amine Guests:  Chiral Discrimination and Their Complex Structures

Abstract

New linear host (1) and cyclic hosts (2 and 3), which have galactopyranose skeletons as chiral origins and oxyethylenes skeletons as binding sites, were designed based on the structural features extracted from the fructo-oligosaccharide derivatives, having a large chiral discrimination ability, and were then synthesized. These hosts showed chiral discrimination toward chiral organic ammonium salts. For example, the chiral discrimination ability (the ratio of association constants: K(R)/K(S)) of host 1, which has the highest value among them, was K(R)/K(S) = 3 for Trp-O-(i)Pr(+) and K(R)/K(S) = 0.7 for 1-(1-naphthyl)ethylammonium (NEA(+)) at 298 K in CHCl(3). It was clarified that host 1 changed the conformation from a linear structure to the pseudo-ring structure by complexation with cations such as alkali metallic ions and chiral organic ammonium ions. The (1)H NMR induced shifts of host 1 by adding the NEA(+) guests showed that the host-guest complex structures are clearly different, depending upon the chirality of the guest; in the complex with (R)-NEA(+), the naphthyl group of the guest is located above the oxyethylene skeleton of the host and in the complex with (S)-NEA(+), and the naphthyl group is located between the edges of the pseudo-ring of the host. The clearly different structure of the complex of host 1 with NEA(+) may be caused by the dynamic molecular recognition, thus the induced-fitting mechanism.

A review of recent advances in mass spectrometric methods for gas-phase chiral analysis of pharmaceutical and biological compounds

“…The gas-phase mass spectrometric methods that have been extensively developed fall into five main categories: (1) the kinetic method formalism , (2) host-guest (H-G) diastereomeric adduct formation [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67], (3) ion/molecule (equilibrium) reactions [68][69][70][71][72][73][74][75], (4) CID of diastereomeric adducts [76][77][78], and (5) the emerging technique of ion mobility spectrometry (IMS) [131][132][133][134][135][136]. These methods along with other mass spectrometric approaches [79][80][81][82][83][84][85][86][87][88][89] provide a fast means for gas-phase chiral analysis.…”

“…Instead, their formation is monitored simply by recording their relative abundances in a mass spectrometer. This method uses simple single-stage MS to follow chiral-inclusion complex formation through host-guest (H-G) interactions [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. Like any single stage MS method it requires that the enantiomeric guest (analyte) be isotopically labeled such that the H-G diastereomeric adduct can be mass-resolved and the ion abundance ratio can be utilized for quantitative chiral analysis.…”

“…Like any single stage MS method it requires that the enantiomeric guest (analyte) be isotopically labeled such that the H-G diastereomeric adduct can be mass-resolved and the ion abundance ratio can be utilized for quantitative chiral analysis. This method is readily implemented using various ionization techniques such as fast atom bombardment (FAB) [54][55][56][57][58][59][60][61][62][63] and ESI [53,64,66]. However, the method is best exploited when the examined samples are pure because MS/MS is not performed.…”

Triazole-linked Host Compounds for Chiral-Discrimination toward Amino Acid Ester Guests

“…Several applicatory methods, such as the kinetic method developed by Cooks and co-workers 9) , the FT-ICR/MS method developed by Lebrilla and co-workers 10) , and the CID method developed by Speranza and co-workers 8) , were used to determine the optical purity of the target compounds. On the other hand, we proposed the fast atom bombardment mass spectrometry/enantio-labeled-guest or -host (FABMS/EL-g or -h) method on the basis of host-guest chemistry [11][12][13] . Using the FABMS/EL-g method, the chiral-discriminating ability of the host was easily evaluated by unspecialized FABMS conditions.…”

“…Alkylated galactose and glucose have been used in linear ether-linked host compounds as chiral inductors [11][12][13] .…”