Stereochemical effects in mass spectrometry XIII—Determination of absolute configuration by fast atom bombardment mass spectrometry

It was found that in the fast atom bombardment mass spectra of some asymmetric secondary alcohols and amines, when a pair of enantiomers, such as (2R,3R)- and (2S,2S)-2,3-diacetoxysuccinic anhydride and (2R,3R)- and (2S,3S)-2,3-dibenzoyloxysuccinic anhydride, were used as reagents, the relative abundances of characteristic ions formed by the stereoselective reaction between a sample and a reagent of different configurations were much higher than those of ions formed by a sample and a reagent of the same configuration. The absolute configurations of the sample molecule may be predicted by examination of the mass spectra of the sample measured with reagents of R and S configurations. This approach proved to be a convenient way to determine the absolute configuration of organic molecules at the micromole level by fast atom bombardment mass Spectrometry, and it has advantages over the chemical ionization method reported previously for the analysis of polar and involatile compounds.     

Stereochemical effects in mass spectrometry XI. Negative ion fast atom bombardment mass spectrometry of saccharides and glycosides using phenylboronic acid as reagent

The negative ion fast atom bombardment (NIFAB) mass spectra of mono-, di-saccharides and glycosides using phenylboronic acid (PBA) as reagent have been studied. In the ion source, PBA reacts stereospecifically with the molecules containing cis-vicinal glycols to form characteristic ions, from which the stereo-isomers of saccharides can be definitely distinguished. Disaccharides and glycosides with β-glycosidic linkage seem to be unfavorabale to react with PBA, therefore, by comparison of the abundances of the characteristic ions, the configuration of the glycosidic linkage in these compounds may be inferred.     

Die Konstitution des Loroglossins. 163. Mitt. über organische Naturstoffe

The Constitution of Loroglossine Loroglossine, a characteristic constituent of orchids, is shown to be bis[4-(β-D -glucopyranosyloxy)-benzyl]-(2R, 3S)-2-isobutyl-tartrate (1) . Base catalysed hydrolysis and esterification with diazomethane gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)- 3 ) and 2 mol-equiv. of a glucoside which after acetylation formed 4 identical with a synthetic sample. The structure of (+)- 3 follows from the synthesis of (±)- 3 by osmium tetroxide oxidation of isobutyl-maleic acid anhydride and subsequent esterification. The absolute configuration of (+)- 3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 15 and 16 and pure 15 with (S)-(+)- and (R)-(?)-α-phenyl-butyric acid, respectively.     

Absolute configuration assignment of ortho,meta, or para isomers by mass spectrometry

A general method based solely on mass spectrometric techniques for the absolute configuration assignment of ortho, meta, or para isomers of acyl nitrobenzenes and derivatives is described. Instead of comparing the mass spectra of the three intact molecules of each positional isomer and investigating each one of the many sets of positional isomers, the method generalizes the effort by performing structural analysis on configurationally diagnostic fragment ions that are common for a given class of compounds. These ions must therefore retain the positional information of the parent molecules and be unequivocally distinguished. Nitrobenzoyl cations are common and stable fragment ions of most acyl nitrobenzenes and derivatives retaining the respective ortho, meta, or para configuration of the precursor molecules. The different NO₂ and CO⁺ ring alignments profoundly influence their collision-induced dissociation and bimolecular reactivity, and the isomeric 2-, 3-, and 4-nitrobenzoyl cations are found to be unequivocally distinguished using both approaches. Absolute ortho, meta, or para positional assignment by tandem MS of every isomeric molecule of the acyl nitrobenzene class and derivatives forming detectable amounts of any of those diagnostic nitrobenzoyl cations is, therefore, possible. The ability to perform absolute (non-comparative) configuration assignment using such diagnostic ions is exemplified for a single test molecule of (2R)-(−)-2-methylglycidyl 4-nitrobenzoate. The general application of this absolute MS-only method for other classes of positional isomers is discussed.     

Diastereomeric differentiation of norbornene amino acid peptides by electrospray ionization tandem mass spectrometry

A new class of diastereomeric pairs of non‐natural amino acid peptides derived from butyloxycarbonyl (Boc‐)protected cis‐(2S,3R)‐ and trans‐(2S,3S)‐β‐norbornene amino acids including a monomeric pair have been investigated by electrospray ionization (ESI) tandem mass spectrometry using quadrupole time‐of‐flight (Q‐TOF) and ion‐trap mass spectrometers. The protonated cis‐BocN‐β‐nbaa (2S,3R) (1) (βnbaa = β‐norbornene amino acid) eliminates the Boc group to form [M+H–Boc+H]⁺, whereas an additional ion [M+H–C₄H₈]⁺ is formed from trans‐BocN‐β‐nbaa (2S,3S) (2). Similarly, it is observed that the peptide diastereomers (di‐, tri‐ and tetra‐), with cis‐BocN‐β‐nbaa (2S,3R)‐ at the N‐terminus, initially eliminate the Boc group to form [M+H–Boc+H]⁺ which undergo further fragmentation to give a set of product ions that are different for the peptides with trans‐BocN‐β‐nbaa (2S,3S)‐ at the N‐terminus. Thus the Boc group fragments differently depending on the configuration of the amino acid present at the N‐terminus. It is also observed that the peptide bond cleavage in these peptides is less favoured and most of the product ions are formed due to retro‐Diels‐Alder fragmentation. Interestingly, sodium‐cationized peptide diastereomers mainly yield a series of retro‐Diels‐Alder fragment ions which are different for each diastereomer as they are formed starting from [M+Na–Boc+H]⁺ in peptides with cis‐BocN‐β‐nbaa (2S,3R)‐ at the N‐terminus, and [M+Na–C₄H₈]⁺ in peptides with trans‐BocN‐β‐nbaa (2S,3S)‐ at the N‐terminus. All these results clearly indicate that these diastereomeric pairs of peptides yield characteristic product ions which help distinguish the isomers. Copyright © 2009 John Wiley & Sons, Ltd.     

Characterization of synthetic N-acetylcysteine conjugates by positive- and negative-ion 252Cf plasma desorption mass spectrometry

N-Acetylcysteine and nine N-acetylcysteine conjugates of synthetic origin were characterized by positive- and negative-ion plasma desorption mass Spectrometry. For sample preparation the electrospray technique and the nitrocellulose spin deposition technique were applied. The fragmentation of these compounds, which are best seen as S-substituted desaminoglycylcysteine dipeptides, shows a similar behaviour to that of linear peptides. In the positive-ion mass spectra intense protonated molecular ion peaks are observed. In addition, several sequence-specific fragment ions (A⁺, B⁺, [Y + 2H]⁺, Z⁺), immonium ions (I⁺) and a diagnostic fragment ion for mercap-turic acids (R_M⁺) are detected. The negative-ion mass spectra exhibit deprotonated molecular ions and in contrast only one fragment ion corresponding to side-chain specific cleavage ([R_XS]^?) representing the xenobiotic moiety. In the case of a low alkali metal concentration on the target, cluster molecular ions of the [nM + H]⁺ or [nM - H]^? ion type (n = 1-3) are observed. The analysis of an equimolar mixture of eight N-acetylcysteine conjugates shows different quasi-molecular ion yields for the positive- and negative-ion spectra.     

Chemical ionization mass spectrometry studies—VII: Deuterium labeled decanes

CI mass spectra of the five isomeric vicinal d₂-decanes have been recorded using methane and d₄-methane as reagent gases. In contrast to earlier suggestions, we find that a large fraction of the alkyl fragment ions from n-decane are formed by elimination of olefins from the abundant [M – 1] ion. Only the C₉ and C₈ fragment ions are produced completely by a one-step reaction between the decanes and the methane reagent ions. Isotope exchange does not occur between the hydrocarbon and the reagent ions derived from d₄-methane but extensive scrambling of the deuterium label in the d₂-decanes does take place in the [M – 1] ion.     

Tetrahydrofurane und Lactone,I. Synthese und Reaktionen chiraler 2,5-überbrückter Tetrahydrofurane – ein neuer Weg zu optisch aktiven γ-Lactonen und γ-Bislactonen

Tetrahydrofurans and Lactones, I. - Synthesis and Reactions of Chiral 2,5-Bridged Tetrahydrofurans - A New Approach to Optically Active γ-Lactones and γ-Bislactones Diels-Alder reaction of 3,4-hexamethylenefuran with acrylic acid gives the carboxylic acid 1a with high endo selectivity. 1a was separated into the enantiomers via the α-phenylethylammonium salts. Comparison of the CD spectra of (−)- 1a and (−)- 3 and the X-ray structural analysis of the camphanoyl derivative (−)- 4b lead to the 1R,2S,4S configuration of (−)- 1a as well. The 2,5-bridged tetrahydrofuran (−)- 5 with all-cis and RSS configuration is obtained by ozonolysis of the ester (−)- 1b . (−)- 5 can be oxidized to the γ-lactone (2R,3S)-(−)- 6 with sodium metaperiodate/potassium permanganate in 22% yield. Hydride reduction of (−)- 6 under various conditions leads to the γ-bislactones (−)- 8 and (−)- 9 or to the bislactol (−)- 10 . (−)- 8 has the same absolute configuration as the naturally occuring (−)-canadensolide.     

Über die Konstitution von Loroglossin. Vorläufige Mitteilung

The Constitution of Loroglossine. Loroglossine, a characteristic constituent of orchids, is shown to be bis-[4-(β-D -glucopyranosyloxy)-benzyl]-(2 R, 3 S)-2-isobutyl-tartrate ( 1 ). Hydrolysis and esterification gave 1 mol-equiv. of dimethyl (+)-2-isobutyl-erythro-tartrate ((+)-3) and 2 mol.-equiv. of a glucoside which, after acetylation, gave 4 , identical with a synthetic sample. The erythro configuration of (+)- 3 by oxidation of isobutyl-maleic acid with osmium tetroxide and subsequent esterification. The absolute configuration of (+)- 3 was based on Horeau experiments and NMR. data of the diastereomeric mixture of its esters 7 and 8 with S (+)- and R (?)-α-phenylbutyric acid respectively.     

Reduction of trinitroaromatic compounds in water by chemical ionization mass spectrometry

A reduction process was found to occur in the ion source when observing the chemical ionization mass spectra of a series of trinitroaromatic compounds, using water as reagent. The [MH–30]⁺ ions in the CI mass spectra were due mainly to the reduction of the compounds to their corresponding amines. This was proved by using D₂O as reagent: the [MH–30]⁺ ions were shifted to [MD–28]⁺ ions. The trinitroaromatic compounds investigated included 1,3,5-trinitrobenzene, 2,4,6-trinitrotoluene, 2,4,6-trinitro-m-cresol, 2,4,6-trinitroaniline (picramide) and 2,4,6-trinitrophenol (picric acid).     

Metastable transitions in the mass spectra of ketals and ketones. Competition between loss of small and large radicals

An investigation of competing metastable transitions in the mass spectra of ethylene ketals R_SR_LC(OCH₂)₂ (where R_L is a larger n-alkyl group than R_S) has established that in most cases R_S is lost with a lower activation energy than R_L. This technique has also been applied to ketones R_SR_LC?O, to show again that R_S is usually lost with the lower activation energy (thus supporting earlier data based on relative daughter ion abundances at the threshold). In the classes of compounds so far investigated, although [M⁺ ? R_S] ions are formed with lower activation energies than [M⁺ ? R_L] ions, the ion yield of [M⁺ ? R_S] ions is anomalously low from ions of high internal energy. Factors which may influence the [M⁺ ? R_S]/[M⁺ ? R_L] ratio of daughter ion intensities are examined. It is suggested that at the threshold [M⁺ ? R_S] and [M⁺ ? R_L] ions may be formed with rearrangement, or from an electronic state that cannot be effectively populated from molecular ions of high internal energies.     

Stoffwechselprodukte von Mikroorganismen. 237. Mitteilung. (2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanon aus zwei Actinomyceten-Stämmen

(2S, 3R, 4R, 6R)-2,3,4-Trihydroxy-6-methylcyclohexanone from Two Strains of Actinomycetes A tetrazolium-blue positive compound was isolated from two strains of acinomycetes. Its constitution and relative configuration 1 were determined by spectroscopic methods, and the absolute configuration by degradation to (+)-(R)-methylsuccinic acid.     

Postcolumn derivatization liquid chromatography/mass spectrometry for detection of chemical-weapons-related compounds

Postcolumn derivatization for liquid chromatography/mass spectrometry (LC/MS) analysis was characterized for detection of some compounds related to chemical-weapons (CW) agents using an Atmospheric Pressure Chemical Ionization (APCI) source. The derivatizing reagents were added directly to the LC eluent flow, and the derivatization reactions occurred in the APCI source under typical operating conditions. The compound S-[2-(diisopropylamino)ethyl] methylphosphonothioic acid was methylated using the derivatizing reagent trimethylphenyl ammonium hydroxide (TMPAH). Methylphosphonic acid was doubly derivatized to form dimethyl methylphosphonate, although the signal for the derivatization product was very sensitive to the amount of TMPAH. Arsenic compounds related to the CW agent lewisite, including chlorovinyl arsonous acid and arsenic (III) oxide, were derivatized using 2-mercaptopyridine. The thiol group reacted readily with the arsenic (III) center and provided a significant improvement in sensitivity relative to the underivatized signal using APCI or electrospray ionization. Triethanolamine and ethyl diethanolamine were derivatized with benzoyl chloride, a commonly used LC derivatizing reagent for alcohols, to modify their mass spectra. Postcolumn derivatization using an APCI source gives an alternative for detecting some difficult-to-ionize compounds. It has the limitations that sensitivity was not always improved even though the major mass spectral peaks can be shifted; it is necessary to carefully select the reagent; and some reagents introduced strong interference peaks at specific masses in the spectrum and may suppress the ionization of some derivatized analyte ions. The reagent also produced contamination in the source, which had to be cleaned daily.     

Circulardichroismus. 62. Mitteilung. Chiroptische Eigenschaften einiger Trimethylcyclohexen-Derivate: Die Jonone,Irone und Abszisinsäuren

The absolute configuration of (+)-α-ionone 3 (R), the absolute configurations at C(6) of (+)-cis-α-irone 5 (6S) and (?)-trans-α-irone 6 (6R), and the absolute configurations of (+)-cis-abscisic acid 10 (S) and (+)-trans-abscisic acid 11 (S) are deduced from the CD.-spectra.     

Synthesis and Stereochemistry of (1S,3S,4S,7R11R)-3-(4-Nitrophenyl)-11-aza-2,6-dioxatricyclo[5,3,1,04,11]undecane

The reaction of (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol with glutaraldehyde has been studied. It has been established on the basis of AM1 and PM3 calculations and ¹H NMR spectra recorded in the presence of the shift reagent Eu(fod)₃ that (1S,3S,4S,7R,11R)-3-(4-nitrophenyl)-11-aza-2,6-dioxatricyclo[5,3,1,0^4,11]undecane is formed as the result of the reaction.     

Chemical properties of marine terpenoids. 1. Some reactions of (6S,10R)-10-bromo-3,11,11-trimethyl-7-methylidenespiro[5,5]undec-2-en-4-one,a sesquiterpenoid from the sea hare Aplysia dactylomela

The structures of products obtained by reductive debromination and CF₃COOH- and KOH-induced transformations of natural chamigrane-type sesquiterpenoid (6S,10R)-10-bromo-3,11,11-trimethyl-7-methylidenespiro[5,5]undec-2-en-4-one (dactylone) isolated from the sea hare Aplysia dactylomela were analyzed. The absolute configurations of the reaction products were established by CD spectra taking into account the configuration of the starting dactylone.     

Electrospray ionization and triple quadrupole tandem mass spectrometry study of some biologically relevant homo- and heterodimeric cadmium thiolate conjugates

A series of 19 compounds of general formula R₁S-Cd-SR₂, R₁, and R₂, being some biologically relevant thiol amino acids and peptides, were prepared by direct reaction of cadmium(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of stoichiometric 1:2 Cd-thiol systems containing either an individual thiol or equimolar mixtures of two different thiols featured several Cd-containing signals, although at much lesser intensity than in the previously reported experiments with mercury(II) (J. Am. Soc. Mass Spectrom. 2004, 15, 288–300). Also, the relative intensity of the homo- and heterodimeric thiolates were significantly different from the theoretically expected 1:2:1 ratio, thus pointing at some degree of discrimination between the different thiols. In particular, homo-cysteine showed much less reactivity than cysteine, and penicillamine and cysteine methyl ester much less than the free amino acid. The fragment spectra show structure-specific ions for the different ligands bound to the metal ion and allow a stand-alone determination of the connectivity also of isomeric pairs. The fragmentation pathways are similar to those observed for the corresponding mercury(II) analogues, with the addition of further intense and specific fragments, one formally carrying a Cd-bound OH ligand and one connected as a five-membered oxazolone carrying a cadmium-bis-thiolate side chain, both formed with a high intensity. Energy-resolved fragmentation data show that metal-free ions can be generated from cysteine but not from glutathione conjugates and point to the possibility of unveiling differences in the biochemical behavior of the conjugates of different heavy metals through the detailed study of their mass spectrometric fragmentation.     

Negative chemical ionization mass spectrometry of phenols,and their determination in acidic fractions of coal-derived liquids

The use of Freon–113 as a reagent gas in the negative chemical ionization mass spectra of phenolic compounds is reported. The dominant mode of ionization is by chloride attachment producing [M + Cl]^? ions. The application of this technique to the highly phenolic acid fractions from coal-derived liquids gives spectra containing essentially only [M + Cl]^? peaks. This allows relative molecular mass profiles to be obtained. The resultant complex spectra are simplified by dividing them into their homologous series components. Since this is a low-resolution technique, absolute component identification cannot be made; but in conjunction with other analytical methods, tentative identification of series of molecules is possible. Thus, the alkyl-substituent ranges of the different homologous series can be assessed. Comparisons between coal-derived liquids produced under different reaction conditions are made, and composition differences detected.     

Bifunctional interaction and its effect on the esterification of dicarboxylic acids in chemical ionization mass spectrometry

The chemical ionization mass spectra of different dicarboxylic acids, including saturated and unsaturated aliphatic, aromatic, hydroxyl and amino-substituted dicarboxylic acids, have been studied using pure methanol as the reagent gas. Biomolecular monoesterification and diesterification product ions [M+15]⁺ and [M+29]⁺, and adduct ion [M+33]⁺, were observed, in addition to the protonated molecule [MH]⁺ and unimolecular water elimination product ions. The formation of a protonated molecule with bridged intramolecular hydrogen bond, and its effect on the esterification of dicarboxylic acids is discussed. Geometric isomers, such as maleic and fumaric acid, and ortho and meta isomers of phthalic acids can be distinguished from each other by methanol chemical ionization mass spectra. When ethanol was used as the reagent gas, similar mass spectra of some dicarboxylic acids were obtained.     

Selective reagents in chemical ionization mass spectrometry: Tetramethylsilane with ethers

Chemical ionization mass spectra of several ethers obtained with He/(CH₃)₄Si mixtures as the reagent gases contain abundant [M + 73]⁺ adduct ions which identify the relative molecular mass. For the di-n-alkyl ethers, these [M + 73]⁺ ions are formed by sample ion/sample molecule reactions of the fragment ions, [M + 73 ? C_nH_2n]⁺ and [M + 73 ? 2CnH_2n]⁺. Small amounts of [M + H]⁺ ions are also formed, predominantly by proton transfer reactions of the [M + 73 ? 2CnH_2n]⁺ or [(CH₃)₃SiOH₂]⁺ ions with the ethers. The di-s-alkyl ethers give no [M + 73] ⁺ ions, but do give [M + H]⁺ ions, which allow the determination of the relative molecular mass. These [M + H]⁺ ions result primarily from proton transfer reactions from the dominant fragment ion, [(CH₃)₃SiOH₂]⁺ with the ether. Methyl phenyl ether gives only [M + 73]⁺ adduct ions, by a bimolecular addition of the trimethylsilyl ion to the ether, not by the two-step process found for the di-n-alkyl ethers. Ethyl phenyl ether gives [M + 73]⁺ by both the two-step process and the bimolecular addition. Although the mass spectra of the alkyl etherr are temperature-dependent, the sensitivities of the di-alkyl ethers and ethyl phenyl ether are independent of temperature. However, the sensitivity for methyl phenyl ether decreases significantly with increasing temperature.