Chiral Recognizable Host-Guest Interactions Detected by Fast-Atom Bombardment Mass Spectrometry: Application to the Enantiomeric Excess Determination of Primary Amines

Abstract

The enantiomeric excess (ee) of organic amine compounds has been determined using fast-atom bombardment (FAB) mass spectrometry based on the chiral host-guest complexation systems. The method uses a 1 : 1 mixture of the given chiral crown ether hosts (H RRRR and H SSSS-dn), one of whose enantiomers is isotopically labeled, for the ee-determination of a given amine salt guest (G +). The peak intensity ratio {I[(H RRRR + G) + ] / I[(H SSSS-dn + G) + ] = IRIS} of the two diastereomeric host-guest complex ions clearly changes with the change in the ee of the guest. The intensity excess (I e) of the two complex ion peaks is newly defined as I e = (IRIS-1) / (IRIS + 1). The two sets of mass spectrometrically obtained I e values vs a set of ee values of phenylalanine methyl ester and leucine methyl ester hydrochlorides show excellent linear relationships through the zero point (R 2 = 0.9989 and R 2 = 0.9970, respectively). This indicates the potential utility of the present ee-determination method to within ± 3% ee. Furthermore, based on the solution equilibrium distributions of the complex ions, the linearity is mathematically justified. Therefore, the ee-determination can be simplified as ee (%) = (|I e | / |I e(100) |) × 100: here, I e(100) is the corresponding I e value obtained using an enantiomerically pure (100% ee) guest as a reference. The present chiral dimethoxyphenyl crown ether host pairs employed are effective (IRIS ≥ 1.5) for the ee-determination of most α-amino acid esters, but not effective (IRIS ≈ 1.0) for most simple alkylamines.

Chiral recognition in NMR spectroscopy using crown ethers and their ytterbium(III) complexes

“…Recrystallization from methanol afforded the triamide derivative based on 1 H NMR analysis (0.266 g, 79%). 1 (4R,9R,17R,22R)-27-bromo-29-methoxy-9,17-diphenyl-3, 10,13,16,23-pentaoxatetracyclo[23.3.1.0 4,9 .0 17,22 ]nonacosa-1 (28), 25(29), 26-triene (22) A solution of diol (R,R,R,R)-21, which was prepared according to the literature [34], (638 mg, 1.40 mmol) and 4-bromo-2,6-bis(bromomethyl)-1-methoxybenzene (523 mg, 1.40 mmol) in dry THF (160 ml) was added dropwise to a boiling mixture of sodium hydride (225 mg, 5.61 mmol) and dry THF (70 ml). The mixture was refluxed for an additional 14 h under dry nitrogen.…”

“…Crown ethers containing a phenol or methoxy group within the cavity (similar to 5) have been utilized for chiral recognition in mass spectrometry [21,22,23] and chromatography [24]. The chiral discriminating and binding properties of these crown ethers have been examined using absorption spectroscopy [25,26] and 1 H NMR spectroscopy [23,27].…”

“…We also describe the utility of amide derivatives of 1 with tryptophan (1a), 1-phenylethylamine (1b), 1-(1-naphthyl)ethylamine (1c), 1-cyclohexylethylamine (1d), and methylamine (1e) as chiral NMR solvating agents. Finally, chiral crown ethers with structures similar to 5 have been previously used for chiral recognition [21,22,23,24,25,26,27,28]. The procedure for preparing 5 is shown in Scheme 1.…”

Improvements in quantitative chiral determinations using the mass spectrometric kinetic method

“…Non-tandem methods generally require isotopically labeled compounds (analyte or chiral reference) and the identification can involve but is not limited to [21][22][23][24][25][26][27] ion-inclusion complex formation, where the analyte of interest complexes with a labeled and an un-labeled chiral host compound [24,26,[28][29][30]. The enantiomers produce different responses that are quantifiable as judged from the ion abundances.…”