Synthesis of chiral monoaza-15-crown-5 ethers from a chiral amino alcohol and enantiomeric recognition of potassium and sodium salts of amino acids

The enantiomeric recognition of chiral monoaza-crown ethers for amino acids as their sodium and potassium salts has been investigated by UV–vis. The highest discrimination was observed for TrpK (d/l = 6.47). The reversed enantioselectivity of chiral monoaza-crown ether II was observed for TrpK.     

Enantioselective transport of amino acids as their potassium and sodium salts by optically active diaza-18-crown-6 ethers having arene sidearms

The enantioselective transport of amino acids as their sodium and potassium salts has been investigated by optically active diaza crown ethers. The reversed enantioselectivity of chiral crown ether 1 was observed.     

Supported liquid membrane separation of amine and amino acid derivatives with chiral esters of phosphoric acids as carriers

Studies on the possible use of phosphate and phosphonate esters bearing chiral menthol or nopol moieties as carriers for the transport of amines, amino acids, and amino acid esters through supported liquid membranes (SLM) are presented. Additionally, the enantioselectivity of the SLM transport of alkyl esters of aromatic amino acids and a non‐protein amino acid was also evaluated. It could be concluded that the extent of transport strongly depends on the hydrophobicity of the amino compound. Moreover, the carrier structure also influences the transport of those compounds through SLM: chiral phosphate and phosphonate esters appear to be poor or moderate carriers for enantioselective SLM transport of amino acids and their esters. The transport efficiency and selectivity is strongly dependent on the structure of both the transported compounds and the carrier. However, no meaningful relationship exists between these structural features and transportation or enantioselectivity.     

Chiral separation of amino acids by capillary electrophoresis with octyl-beta-thioglucopyranoside as chiral selector

In the present work, we propose the use of direct coupling of a headspace sampler to a mass spectrometer for the detection of adulterants in olive oil. Samples of olive oils were mixed with different proportions of sunflower oil and olive-pomace oil, respectively, and patterns of the volatile compounds in the original and mixed samples were generated. Application of the linear discriminant analysis technique to the data from the signals was sufficient to differentiate the adulterated from the non-adulterated oils and to discriminate the type of adulteration. The results obtained revealed 100% success in classification and close to 100% in prediction. The main advantages of the proposed methodology are the speed of analysis (since no prior sample preparation steps are required), low cost, and the simplicity of the measuring process.     

Synthesis of new chiral imidazolium salts derived from amino acids: their evaluation in chiral molecular recognition

A family of new imidazolium salts derived from natural amino acids has been synthesized and tested for NMR enantiodiscrimination, as chiral shift reagents, of carboxylic acids. These imidazolium receptors contain different structural modifications and the splitting of the signals of the acids, after addition of the corresponding CSRs, depends on these structural variables. Compound 8b exhibited the strongest chiral solvating properties for racemic Mosher acid and was recognized as a suitable CSR for the determination of its enantiomeric composition.     

Lariat ethers. VI. Evidence for intramolecular chelation in sodium and potassium cation binding by 15-crown-5, carbon-pivot lariat ethers

The first compelling evidence for intramolecular sidearm involvement in sodium and potassium cation complexation by carbon-pivot lariat ethers is presented.     

Solution complexation between potassium iodide and lariat ethers having pi-donor sidearms

Experimental evidence is presented for the interaction of triple bond pi-donors with potassium cation in acetonitrile solution.     

Chiral amines as reagents for HPLC-MS enantioseparation of chiral carboxylic acids

Mass spectrometry (MS) has become a popular analytical technique because of its high sensitivity and specificity. Therefore, the use of a chiral derivatization reagent for the MS detection seems to be efficient for the enantiomeric separation of racemates. However, the number of chiral reagents for the liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis is very limited. The applicability of commercially available chiral amines as the derivatization reagents for the enantiomeric separation of chiral carboxylic acids is reported in this paper by using non-steroidal anti-inflammatory drugs (NSAIDs), i.e. ibuprofen, flurbiprofen, and loxoprofen. The efficiency of the chiral reagents was evaluated in terms of tagging easiness, separation by reversed-phase chromatography, and detection sensitivity by electrospray ionization (ESI)-MS/MS. Among the tested eight chiral amines, i.e. (R)-(+)-4-(3-aminopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-APy), (S)-(+)-1-(2-pyrrolidinylmethyl)-pyrrolidine (PMP), L-prolinamide, (3R)-(-)-1-benzyl-3-aminopyrrolidine, (S)-(+)-1-cyclohexyl-ethylamine, (3R)-(+)-3-(trifluoroacetamido)-pyrrolidine (TFAP), (R)-(-)-1-aminoindan (AI), and (S)-(+)-tetrahydrofurfuryl-amine, DBD-APy, PMP, AI, and TFAP could be used as the chiral reagents for the enantiomeric separation of the NSAIDs. The Rs values and the detection limits of the derivatives were in the range of 1.29-3.85 and 0.57-0.96 fmol, respectively. These four reagents were applied for the determination of the NSAIDs in rat plasma.     

Zwitterionic amino acids as precursors for nonmetal cation pentaborate salts

Nonmetal cation (NMC) pentaborate structures were synthesized using the amino acid molecules as cations precursors. Chemical composition analysis, infrared spectroscopy, mass analysis, boron nuclear magnetic resonance, and thermal gravimetric analysis (TGA/DTA) methods were used for structural characterization. The hydrogen storage efficiency of molecules was also determined experimentally. The recorded infrared spectra support the structural similarities of the molecules. Stretchings of pentaborate rings and characteristic peaks of amino acids were detected in infrared spectra. When the thermal analysis curves were recorded, it was found that the structures showed similar decomposition steps. Due to the result of thermal decay, glassy boron oxide (B₂O₃) formation was observed as the final decomposition products of all molecules. Peaks associated with boric acid, triborate, and pentaborate were observed in the ¹¹B spectra of these salts. Powder X-ray diffraction spectroscopy supports the presence of BO₃ and BO₄⁻ groups regarding the presence of pentaborate rings. It also indicates the high crystallinity of the structures. The molecular cavities detected by brunauer–emmett–teller analysis were found to be 3.586, 1.922, 1.673, and 1.923 g/cm³. Low-molecular cavities can be attributed to the high hydrogen-bonding capacity of the structures. The hydrogen capture efficiency of the pentaborate salts was found to be in the range of 0.039-0.     

Chiral capillary electrophoretic separation of amino acids derivatized with 9-fluorenylmethylchloroformate using mixed chiral selectors of beta-cyclodextrin and sodium taurodeoxycholate

Chiral separation of 19 pairs of amino acid (AA) enantiomers derivatized with 9-fluorenylmethylchloroformate (FMOC) was successfully conducted by capillary electrophoresis using the mixture of beta-CD and sodium taurodeoxycholate (STDC) as selectors. Resolution was considerably superior to that obtained by using either beta-CD or STDC alone. After a systematic inspection, a buffer composed of 150 mM borate and 18% v/v isopropanol at pH 8.0, dissolved with 30 mM beta-CD and 30 mM STDC, was adopted and able to generate baseline resolution (>1.50) for 17 pairs of FMOC-AA enantiomers and somewhat lower resolution for arginine (1.36) and alanine (1.18), respectively. Experimental data revealed that the addition of the second selector did not increase the mobility difference between a pair of enantiomers (Delta mu = mu(D) - mu(L) and the number of theoretical plates (N), but decreased the summed apparent mobility of a pair of enantiomers (Sigma mu = mu(D) - mu(L)), which was mainly due to the decrease of the electroosmotic flow. The variation of Sigma mu was thus the major reason responsible for the improvement of chiral resolution in this study. The result demonstrated that not only the intrinsic selectivity of the selectors was the basis of the chiral separation, but also the non-chiral effect of the selectors, the change of the electroosmotic flow, was an important factor in enhancing the enantioseparation resolution. This study could probably help to explain the reasons for resolution improvement in some dual selectors systems, which are not very clear at present.     

Guanidinium receptors as enantioselective amino acid membrane carriers

A number of artificial carriers for the transport of zwitterionic aromatic amino acids across bulk model membranes (U-tube type) have been prepared and evaluated. 1,2-Dichloroethane and dichloromethane were employed in the organic phase. All compounds are based on a bicyclic chiral guanidinium scaffold that ideally complements the carboxylate function. The guanidinium central moiety was attached to crown ethers or lasalocid A as specific subunits for ammonium recognition as well as to aromatic or hydrophobic residues to evaluate their potential interaction with the side chains of the guest amino acids. The subunits were linked to the guanidinium through ester or amide connectors. Amides were found to be better carriers than esters, though less enantioselective. On the other hand, crown ethers were superior to lasalocid derivatives. As expected, transport rates were dependent on the carrier concentration in the liquid membrane. Reciprocally, enantioselectivities were much higher at lower carrier concentrations. The results show that our previously proposed three-point binding model (J. Am. Chem. Soc. 1992, 114, 1511-1512), involving the participation of the aromatic or hydrophobic residue to interact with the side chains of the amino acid guest, is unnecessary to explain the high enantioselectivities observed. Molecular dynamics fully support a two-point model involving only the guanidinium and crown ether moieties. These molecules constitute the first examples of chiral selectors for underivatized amino acids acting as carriers under neutral conditions.     

Thermal analysis of nitraminocarboxylic acids and their sodium and barium salts

The thermal stabilities of nitraminomonocarboxylic acids, nitraminodicarboxylic acids, and their monosodium, disodium and barium salts were studied. The effects of the position of the nitramino group and the aliphatic chain length on the decomposition temperature peak and thepK and (pK₂-pK₁) values were followed. The experimental results revealed that the thermal stabilities of the acids and theirpK values are influenced by the relative position of the nitramino group in the molecule. The thermal stabilities of acids and salts increase with increasing chain length. A lower value ofpK was found to correspond to a lower thermal stability of the acids. Barium salts of nitraminodicarboxylic acids were subjected to drop-hammer sensitivity and nearly all of them were found to grow more active.

---

Zusammenfassung Die thermische Stabilität einer Reihe von Nitraminomonokarbonsäuren, Nitraminodikarbonsäuren und ihrer Mononatrium-, Dinatrium- und Bariumsalze wurde geprüft. Es wurde der Einfluß der Nitraminogruppe und der Länge der aliphatischen Kette auf die Lage des Spitzenwertes der Zersetzungstemperaturen undpK-Werte, beziehungsweise (pK₂-pK₁) der Säuren, untersucht. Die Messergebnisse zeigten, daß die thermische Stabilität der Säuren ebenso wie ihrepK-Werte durch die relative Lage der Nitraminogruppe in Molekül beeinflußt wird. Die thermische Stabilität von Säuren und Salzen nimmt mit zunehmender Kettenlänge zu. Als allgemein erwiesen gilt, daß der niedrigerepK-Wert einer niedrigeren thermischen Stabilität der Säuren entspricht. Die Bariumsalze der Nitraminodikarbonsäuren wurden der Empfindlichkeitsprobe mit dem Fallhammer-Apparat unterworfen. Es wurde ermittelt, daß es fast bei allen zur Aktivierung kommt.

---

Résumé La stabilité thermique d'une série d'acides nitraminomonocarboxyliques, nitraminodicarboxyliques et de leurs sels monosodiques, bisodiques et barytiques a été étudiée. On a suivi l'influence du groupe nitramino et de la longueur de la chaine aliphatique sur la position du maximum de la température de décomposition et de la valeur dupK, respectivement (pK₂-pK₁) des acides. Les résultats des mesures ont montré que la stabilité thermique des acides et les valeurs dupK sont influencées par la position realtive du groupe nitramino dans la molécule. La stabilité thermique des acides et des sels augmente avec la longueur de chaine. Il est généralement vérifié qu'une valeur faible dupK correspond à une stabilité thermique plus faible des acides. Les sels de baryum des acides nitraminodicarboxyliques ont été soumis à un essai de sensibilité au marteau tombant. On a établi que presque tous y subissent une activation.

---

- , , . (p₂-₁) . , . . , . . , .

---

---

The authors owe their thanks to research officers of the Department of General and Inorganic Chemistry, and to workers of the Thermal Analysis Centre, both at the University of Chemical Technology in Pardubice, for the DTA and TG measurements, and to the research officers of VÚPCH, VCHZ n.p. Synthesia Semtín for sensitivity measurements on the barium salts.     

Correlation of bilayer membrane cation transport and biological activity in alkyl-substituted lariat ethers

Dialkyldiaza-18-crown-6 lariat ethers having twin n-octyl, n-decyl, n-dodecyl, n-tetradecyl, n-hexadecyl, 1-oxodecyl and 1-oxododecyl side arms were prepared and studied. Cation transport in liposomes mediated by these compounds showed discontinuous activity that correlated with toxicity to the bacteria E. coli and B. Subtilis, and the yeast S. Cerevisiae. Transport, toxicity and membrane depolarization studies all suggest that side chain length affords very different interactions in a bilayer membrane compared with bulk phases. An explanation for activity in terms of carrier transport and restricted transverse relaxation is proposed.     

Chiral bisimidazolium salts derived from amino acids and their palladium(II)- and platinum(II)-biscarbene complexes

We report new chiral bisimidazolium salts synthesized from naturally occurring l-amino acids. They served as precursors for bidentate N-heterocyclic carbene metal complexes. The chiral imidazoles could be synthesized in good yields via a one-pot ring closing reaction, followed by esterification. The methylene bridged bisimidazolium iodide salts are accessible in moderate yields. Corresponding palladium(II)- and platinum(II)-NHC complexes could be synthesized and fully characterized, but do not show optical activity. We also report a solid state structure of one of the synthesized palladium(II) biscarbene compounds derived from alanine.     

Bis-substituted benzo-15-crown-5 ethers as ion carriers in potassium ion-selective electrodes

Lipophilic bis-substituted ester and ether derivatives of benzo-15-crown-5 have been synthesised. The correlation between the structure and potentiometric ion-selectivity has been studied in PVC membrane ion-selective electrodes. An ion-selective potassium sensitive electrode based on 4,5-bis (biphenyloxymethyl)benzo-15-crown-5 exhibited the best electrode properties. The detection limit was loga _K = -5.4; logK _K,Na ^ppot = -3.5. The effect of the lipophilicity of neutral carriers upon electrode performance has been also discussed.     

Chiral macrocycles,part I: Synthesis and enantioselective transport of carboxylic acids as their Li+ salts

A new series of tetrapyrazolic macrocycles with a functionalized sidearm has been prepared. Their capability to transport Li⁺ salts of carboxylic acids has been examined and is shown to be strongly dependent on the functionality of the macrocycle sidearm. In the case of the Li⁺ (D, L.)-mandelate, chiral recognition has been observed.     

Enantiomer separation of amino acids as their N-alkyloxycarbonyl alkylamide derivatives by chiral phase capillary GC

The enantiomers of amino acids were first converted into N-alkyloxycarbonyl 2,2,2-trifluoroethyl esters, and then into N-alkyloxycarbonyl alkylamides by nucleophilic substitution of the ester group with amines. The first reaction proceeds instantaneously, while the second substitution occurs smoothly with n-propylamine and isobutylamine. The final derivatives were produced for separation on a capillary column coated with Chirasil-Val by GC. Pro, which is difficult to separate completely as its N-perfluoroacyl alkyl ester derivative, showed complete separation of the enantiomeric pair. All amino acids examined in this study showed an increased separation factor.     

Asymmetric synthesis of beta-hydroxy amino acids via aldol reactions catalyzed by chiral ammonium salts

The Cinchona alkaloid derived chiral ammonium salt developed by Park and Jew functions as an effective catalyst for the synthesis of beta-hydroxy alpha-amino acids via asymmetric aldol reactions under homogeneous conditions. The syn diastereomers are obtained in good ee, and aryl-substituted aliphatic aldehydes are the best substrates for the reaction. These results represent the highest ee's obtained to date in direct aldol reactions of glycine equivalents catalyzed by inexpensive, readily prepared chiral ammonium salts.