Diastereochemical differentiation of some cyclic and bicyclic β-amino acids, via the kinetic method

Stereochemical differentiation of five diastereomeric pairs of β-amino acids, di-endo- and di-exo-2,3-disubstituted norbornane and norbornene amino acids, cis- and trans-2-aminocyclohexane-, 2-amino-4-cyclohexene-, and 2-aminocyclopentanecarboxylic acids, was investigated via the kinetic method with metal-bound trimeric complexes. This is the first time that diastereomers (di-endo/di-exo and cis/trans) have been differentiated with metal-bound trimeric complexes and the kinetic method. Moreover, determination of diastereochemical excess by the kinetic method was applied to norbornane β-amino acids and cyclopentane β-amino acids. Experiments showed that a remarkable differentiation of the studied diastereomers was achieved. It was observed that better selectivity values correlated to more rigid structures. The reference compounds for the studied β-amino acids varied from α-amino acids to some β-amino acids. In addition, variation of the metal ion (Cu²⁺ and Ni²⁺) had some role in the selectivity values obtained. Ab initio and hybrid density functional theory calculations were performed to clarify the results obtained by mass spectrometry.     

Chiral differentiation of some cyclopentane and cyclohexane β-amino acid enantiomers through ion/molecule reactions

Chiral differentiation of four enantiomeric pairs of β-amino acids, cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane β-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane β-amino acids) was performed successfully by using host-guest complexes and ion/molecule reactions. The experiments were conducted by using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The effect of a chiral host molecule was tested by using three different host compounds; (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, (−)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, and β-cyclodextrin. This is the first time that small enantiomeric pairs with two chiral centers have been differentiated using ion/molecule reactions and host-guest complexes.     

Synthesis, 1 H, 13 C, 15 N, and 113 Cd NMR, ESI-TOF MS, Semiempirical MO (PM3), ab initio/HF and Cation/Anion Binding Studies of N-deoxycholyl-l-tryptophan

The synthesis, structural characterization, and cation/anion binding properties ofa new bile acid-amino acid conjugate, N-deoxycholyl-l-tryptophan, aredescribed. The structures of the ligand and its cadmium adduct at different pHconditions and various cadmium perchlorate concentrations were determined bymodern multinuclear magnetic resonance spectroscopic as well as ESI-TOF MStechniques. Also semiempirical PM3 and ab initio/HF molecular modellingstudies were performed. Based on ¹H,¹H NOESY measurementsN-deoxycholyl-l-tryptophan in alkaline conditions was found to appearin a bent conformation which was clearly different from the conformations in neutraland acidic solutions. According to molecular modelling in its minimum energy structurethe tryptophan backbone of the ligand was folded close to the deoxycholic acid skeletonand the structure was stabilized by an intramolecular hydrogen bond. The multinuclearmagnetic resonance experiments indicated that Cd²⁺-cation was bound with theligand in neutral and alkaline conditions while in acidic conditions protons block thebinding site. ESI-TOF MS revealed clearly a competition between sodium and cadmiumions, the ligand having a stronger affinity for sodium. Cadmium binding occurred onlywhen excess of cadmium was used. Further, ESI-TOF MS spectra showed that variouschlorine oxyanions originated from perchlorate anion formed together with cationsdifferent adducts with the ligand.     

Chemical ionization mass spectra of simple 1,3-dioxolanes and their sulphur analogues recorded with methane,isobutane, ammonia and acetone as reagent gas

The mass spectral behaviour of nine 1,3-dioxolanes, seven 1,3-dithiolanes and seven 1,3-oxathiolanes was studied under chemical ionization conditions with ammonia, isobutane, methane, acetone, acetone-d₆ or pentan-3-one as reagent gas. The proton affinity of the first members in each series was not large enough for ammonia to protonate them; instead, the ionization took place through unstable [M + NH₄]⁺ ions. Isobutane, which gave rise to abundant [M + H]⁺ ions in all cases, was the best reagent gas for the determination of the molecular mass. Methane chemical ionization caused extensive fragmentations either through ring cleavage or through the elimination of the largest substituent from ring positions 2 as a neutral hydrocarbon. The ketones used as reagent gas reacted to form adduct ions. In the case of dioxolanes and oxathiolanes, the [M + RCO]⁺ adduct ion decomposed through ring opening and then, as a consequence of intramolecular nucleophilic substitution, through the elimination of a neutral carbonyl compound. Resonance-stabilized dioxolanylium and oxathiolanylium ions were obtained for dioxolanes and oxathiolanes, respectively. This reaction was almost non-existent for the dithiolanes.     

Electron and chemical ionization mass spectrometry in stereochemical differentiation of some 1,3-amino alcohols

Mass spectral fragmentations of two cyclopentane, eight cyclohexane and four norbornane/one 1,3-amino alcohols were studied under electron ionization (EI) by low-resolution, high-resolution, metastable ion analysis and collision-induced dissociation (CID) techniques. All stereoisomeric compounds gave rise to identical 70 eV EI mass spectra. However, the spectra of positional isomers clearly differed. The main fragmentation pathway for the saturated compounds began as an α-cleavage reaction with respect to the nitrogen atom. For the norbornene compounds a retro-Diels—Alder reaction was favoured. Relative to the aminomethyl-substituted compounds the fragmentation patterns for the compounds having the amino group connected directly to the ring were more complicated. The chemical ionization (CI) mass spectra were recorded using ammonia, isobutane, methane, dichloromethane and acetone as reagent gas. From the norbornane/One compounds the di-exo isomers decomposed more easily than the di-endo isomers with most of the reagent gases used. Differences between stereoisomers were observed directly only under methane CI. The decomposition products of the [M + H]⁺ ions generated under ammonia and isobutane CI were studies by recording their CID mass spectra. These spectra allowed the differentiation of the stereoisomers, at least to some extent.     

Mass spectrometric behaviour of cyclopentane-and cyclohexane-condensed pyrimidinediones under electron impact

Mass spectral fragmentations of four cyclopentane-condensed cis-pyrimidinediones and of six cyclohexane-condensed cis- or trans-pyrimidinediones were examined using metastable ion analyses and exact mass measurements. The fragmentation patterns of all of these compounds were clearly different and also cis- and trans-fused isomers were easy to distinguish from each other by their mass spectra. In spite of the differences in their mass spectral fragmentations, all compounds formed phenylisocyanates (m/z 119 and 153) and anilines (m/z 93 and m/z 127), the structures of which were verified by collision-induced dissociation experiments.     

Laccase-catalyzed mediated oxidation of benzyl alcohol: the role of TEMPO and formation of products including benzonitrile studied by nanoelectrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Substituted benzyl alcohol was oxidized enzymatically with a laccase-mediator system and the products were investigated as a function of time by nanoelectrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (nanoESI-FTICRMS). With Trametes versicolor laccase (TVL), the mediator, 2,2',6,6'-tetramethylpiperidine-N-oxyl radical (TEMPO), undergoes oxidation and forms oxoammonium ion. Oxidized TEMPO oxidizes the alcohol and is simultaneously reduced to the N-OH form. The laccase then restores TEMPO back to the normal radical form and the oxidation cycle starts again. The role of TEMPO and the structures of its oxidized and reduced forms in the enzymatic oxidation process were clarified in collision-induced dissociation experiments and gas-phase hydrogen/deuterium (H/D) exchange reactions. The amounts of enzyme and mediator were significant for product formation: with greater amounts overoxidation products, the corresponding benzoic acid and benzonitrile were formed. Smaller amounts of laccase and mediator generated benzaldehyde in high yield. The reaction pathway for benzonitrile formation is discussed and it is suggested to start from benzaldehyde and the ammonia in the ammonium acetate buffer.     

Studies on the biomimetic preparation of the sarpagan ring system. Attempts to apply the spontaneous “biogenetic-type cyclization” of van Tamelen to bond formation between C-5 and C-16 in the corynantheine series

Attempts were made to apply the spontaneous “biogenetic-type cyclization” of van Tamelen to the preparation of the sarpagan ring system by utilizing indolo [2,3-a]quinolizidines 10, 11, 12, and 14. The fact that the spontaneous “biogenetic-type cyclization” did not take place casts some doubt on the correctness of the earlier results.     

Mass spectrometric studies of benzoxazine resorcarenes

Eleven differently substituted 3,4-dihydro-2H-1,3-benzoxazine resorcarenes were studied by electrospray ionisation (ESI) and matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry, using Fourier transform ion cyclotron resonance (FT-ICR) and time-of-flight (TOF) mass spectrometers, respectively. Under ESI conditions it was possible to transfer the intact resorcarenes from solution to the gas phase, yielding [M + H](+) and [M + 2H](+) ions as the main ions observed. Energy increase of the ions induced ready decomposition through successive eliminations of four CH(2)NR groups. Ion-molecule reactions showed that the ionising proton was situated somewhere inside the molecule and could not be reached with neutral reagent gases. In the host-guest complexation experiments, the benzoxazine resorcarenes studied turned out to be poor hosts for alkali metal and ammonium ions. In MALDI experiments, 2,5-dihydroxybenzoic acid proved to be the best matrix for these compounds. However, the intensity of the [M + H](+) ions was low for all compounds, and extensive fragmentation with consecutive elimination of CH(2)NR groups was observed.     

Electron ionization mass spectra of some 4β-phenyl-substituted cycloalkane-cis-fused 1,3-oxazin-2(3H)-ones, -2(3H)-thiones and 1,4-oxazepin-3(4H)-ones

The 70 eV mass spectra of 4β-phenyl-substituted cyclopentane- and cyclohexane cis-fused 1,3-oxazin-2(3H)-ones, the two related 2-thiones, 6,7-cis-trimethylene-5β-phenyl-1,4-oxazepin-3(4H)-one and its 2β-methyl derivative were recorded and their fragmentations examined by means of metastable ion analysis, collision induced dissociation technique and exact mass measurement. The fragmentation patterns of the 1,3-oxazin-2(3H)-ones were relatively simple: the favored formation of cycloalkene ions implied that a considerable proportion of the molecular ions might possess an enol structure. Changes in the size of the fused cycloalkane ring had little or no effect on the fragmentations. Instead, small changes in the heterocyclic part of the molecule caused remarkable effects on the fragmentation behavior. Compared to 1,3-oxazin-2(3H)-ones studied, both 1,3-oxazine-2(3H)-thiones and 1,4-oxazepin-3(4H)-ones showed much more complicated fragmentation patterns.