Isomalt, a commercial sugar alcohol widely used as a sweetener, is approximately a 1:1 mixture of two diastereomers, -D-glucopyranosyl-1-6-mannitol (GPM) and -D-glucopyranosyl-1-6-sorbitol (GPS). A calorimetric investigation has been carried out on mixtures of isomalt with GPS, in the (molar) composition range 0.45<xGPS<1, for both crystalline and amorphous states.The GPS-rich portion of the solid-liquid GPM/GPS phase diagram was established and discussed in light of the existing literature. New evidence was given for the non-ideality of GPM/GPS mixtures, by indicating excess interactions in the melt and/or in the solid state. The commonly accepted hypothesis of a simple GPM/GPS eutectic forming isomalt was refuted in favour of more complicated mixture behaviour with possible formation of a complex.Glass transition and physical ageing of isomalt and GPS were re-visited, with peculiar attention given to the measurement conditions. Standard thermal histories were adapted to each sample and the fictive temperature was used for the characterisation of the structural glass states. A linear increase of the fictive temperature was found upon passing from pure GPS to xGPS=0.45. GPS showed a slightly higher enthalpy relaxation rate than isomalt.
A simple and rapid method has been established for indirect separation of the enantiomers of (R,S)-metoprolol and (R,S)-carvedilol by reversed-phase TLC. Beta blockers derivatized with 1-fluoro-2,4-dinitrophenyl-5-l-alanine amide (Marfey’s reagent, FDNP-l-Ala-NH2) and its six structural variants (FDNP-l-Phe-NH2, FDNP-l-Val-NH2, FDNP-l-Pro-NH2, FDNP-l-Leu-NH2, FDNP-l-Met-NH2, and FDNP-d-Phg-NH2) were spotted on precoated plates. (R,S)- Metoprolol and (R,S)-carvedilol were isolated from pharmaceutical dosage forms and purified. The diastereomers were separated most effectively by use of mobile phases containing acetonitrile and triethylamine-phosphate buffer (50 mM, pH 5.5). The results obtained by use of Marfey’s reagent were compared with those obtained by use of the other variants. The effects of buffer concentration, pH, and concentration of organic modifier were studied.
Authors:Mieczysław Sajewicz, Robert Piętka, and Teresa Kowalska
Chiral separations by gas and liquid chromatography (thin-layer chromatography included) remain an analytical challenge, hence even moderate success in this field is very likely to be regarded as a valuable separation achievement. There has been only one literature report of chiral separation of
-(−)-ibuprofen by TLC. The original procedure was performed with laboratory-coated glass plates and resolution of the two enantiomers in one-dimensional mode was incomplete. In an attempt to enhance the resolution the authors made use of less convenient and considerably more time-consuming two-dimensional TLC and the final result was not very impressive (Δ
= 0.03). These chromatograms were visualized by exposure of the developed plates to iodine vapor and no direct confirmation of the identity of the two chromatographic bands was produced.The goals of this study were: (i) to adapt the experimental conditions used for this separation to commercial chromatographic glass plates; (ii) to enhance the resolution of the two antipodes; and (iii) to produce up-to-date UV spectroscopic evidence of successful separation.
A sensitive and stereoselective high-performance liquid chromatography (HPLC) method based on diastereomer formation was developed and fully validated for the simultaneous determination of the two enantiomers of Baclofen. (S)-Naproxen was used to prepare three chiral derivatizing reagents (CDRs) which were used for synthesizing diastereomers of Baclofen. The diastereomers so synthesized were separated on C18 column under reversed phase conditions using a binary mixture of acetonitrile and triethylammonium phosphate, with UV detection at 220 nm. The results obtained for enantioseparation of Baclofen using the three CDRs have been compiled and compared. The conditions for derivatization and chromatographic separation have been optimized. The method was validated for linearity, repeatability, limits of detection, and limit of quantification.
A high-performance liquid chromatographic (HPLC) method was developed for enantioresolution of amino alcohols using an indirect approach. Two sets of chiral derivatizing reagents (CDRs) having amino acids (CDRs 1–4; set A) and their amides (CDRs 5–8; set B) as chiral auxiliaries in cyanuric chloride (CC) moiety were synthesized and characterized. Diastereomers of eight amino alcohols were synthesized, under microwave irradiation, using each of the eight CDRs. The resulting diastereomers were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) using C18 column and eluting mixtures of acetonitrile with aqueous trifluoroacetic acid (aq.TFA) in a linear gradient (45 min) with UV detection at 230 nm. The results (in terms of resolution Rs and retention factor k) obtained for the two sets of diastereomers were compared among themselves and among the two groups. The effects of chiral auxiliaries (in terms of acid and amides variants), constituting CDRs, on separation were also evaluated. The elution order for the diastereomers was determined. The separation method was validated for limit of detection (LOD), linearity, accuracy, precision, and recovery.
A reversed phase high-performance liquid chromatographic method has been established for enantioseparation of (R, S)-mexiletine. Two volatile and thermally stable acyl chlorides, viz., (S)-(—)-(N)-trifluoro acetyl prolyl chloride and (1S)-(—)-camphanic chloride, were used as chiral derivatizing reagents. Binary composition of aqueous trifluoroacetic acid (0.1%)-acetonitrile as mobile phase was successful with ultraviolet (UV) detection at 210 nm. The method was optimized and validated for accuracy, precision, and limit of detection. The limit of detection was found to be 45 ng mL−1 and 80 ng mL−1 for the two types of diastereomers. Besides, kinetic resolution was achieved, and the experimental conditions optimized for this purpose provided diastereomeric excess up to 74% for (R)-isomer. On achieving a resolution value greater than 2, the optimized method for analytical enantioseparation was scaled-up to smallscale preparative level, and the native (R)-mexiletine was recovered by acid hydrolysis of the diastereomer.
Authors:V Vargha, O Vorster, Zs Finta, and G Csuka
The gelation of a powder coating and its matrix based
on a saturated carboxyl functional polyester resin and triglycidyl isocyanurate
of different diastereomer racemate composition was investigated by rotational
viscometry. The iso-Tcure
diagrams have been determined directly by isothermal viscometric measurements
and the gelation curves for the TTT-diagram
have been constructed. To the measured section of the gelation curves power
functions could be fitted and with their help the reactivity of the investigated
systems were compared. The ratio of the two diastereomer racemates of TGIC
has a significant effect on the reactivity of the coating, as it was also
supported by DSC measurements. β-TGIC is of highest reactivity, and by
increasing its ratio in TGIC, reactivity increases, and adversely effects
the performance of the powder coating. Commercial TGIC-s have similar reactivity,
comparable to that of high α-TGIC. The reactivity of the matrix is higher
than that of the powder.
Authors:Adrian Beteringhe, Ion Baciu, Miron Caproiu, Titus Constantinescu, and Alexandru Balaban
(1b and 2b, respectively) and
diastereomers (1c and 2c, respectively) of the
-methyloximes of testosterone (1a) and 17
-methyltestosterone (2a) have been synthesized and separated by TLC.
H NMR assignments confirmed the corresponding structures. The TLC
values of these six compounds could be rationalized by a quantitative structure-property relationship (QSPR) using one topological/topographical index.
The enantiomers of serine have been separated after pre-column derivatization with ortho-phthaldialdehyde (OPA) and N-tert-butyloxycarbonyl-l-cysteine (Boc). Analysis of the enantiomers of amino acids after pre-column derivatization with OPA-Boc has been reported in the literature but no critical evaluation has been carried out. In this study, decomposition of the diastereomers, effect of the sample pH, and amount of derivatization agent were studied; the half life of the decomposition was also determined. The method was used for analysis of D and l-serine from three different areas of rat brain (the striatum, prefrontal cortex, and cerebellum).
Two new structural variants of Marfey's reagent (1-fluoro-2,4-dinitrophenyl-5-l-alaninamide, FDNP-l-Ala-NH2) were synthesized by nucleophilic substitution of one fluorine atom in 1,5-difluoro-2,4-dinitrobenzene (DFDNB) by l-methioninamide or d-phenylglycinamide. The new variants FDNP-l-Met-NH2 and FDNP-d-Phg-NH2 were characterized and used for derivatization of twenty-six α-amino acids. The resulting diastereomeric derivatives were separated on a reversed-phase C18 HPLC column using a linear gradient of acetonitrile and aqueous trifluoroacetic acid (TFA) and the results were compared with those obtained by use of Marfey's reagent. To determine and establish the efficiency of both the new variants, separation results were compared for diastereomers of five representative amino acids (Ala, Phe, Ser, Asp, and Asn) prepared with MR, FDNP-l-Phe-NH2, FDNP-l-Val-NH2, FDNP-l-Leu-NH2, and FDNP-l-Pro-NH2, experiments being performed under identical conditions. Both the new chiral reagents enabled better separation of the diastereomers than Marfey's reagent for most of the amino acids. The reagent FDNP-d-Phg-NH2 enabled excellent separation for serine and asparagine whereas other reagents failed or provided poor results.