Grazia Principato

Facile separation of the enantiomers of diethyl N-(aryl)-1-amino-1-arylmethanephosphonates on a rationally designed chiral stationary phase

Separation of the enantiomers of each member of a series of diethyl N-(aryl)-1-amino-1-arylmethanephosphonates is easily accomplished by HPLC using a WHELK-O column. This totally synthetic chiral stationary phase (CSP 1) is designed to utilize specifiable interactions to differentiate between enantiomers. The structural features of these phosphonates suggested that CSP 1 would be applicable to the separation of the enantiomers of this class of compounds even though there was an element of uncertainty owing to the presence of two π-basic interaction sites, one on either side of the stereogenic center. The structures of the π-basic N-aryl and C-aryl substituents have been varied, the structure of the latter being found to have the greatest effect on retention and enantioselectivity.

Inherently chiral α-picolyloxy-p-tert-butylcalix[5]arene crown ethers: Synthesis, structure proof, and enantioselective HPLC resolution

Abstract Reaction of α -picolyloxy- p - tert -butylcalix[5]arene with tri- to pentaethylene glycol ditosylates and K 2 CO 3 regioselectively affords racemic (1,2)-bridged crown ether derivatives in the cone conformation. Their structure is firmly established by NMR spectroscopy and by comparison with appropriate (1,3)-bridged crown-6 regioisomers, synthesized by unequivocal sequences. The enantiomeric resolution of racemates has been achieved by direct HPLC separation, using enantioselective stationary phases. The enantiomers of the (1,2)-bridged crown-5 derivative exhibit one of the largest separation factors (α) so far reported for inherently chiral calixarenes.

Resolution of inherently chiral 1,4-2,5-calix[8]bis-crown-4 derivatives by enantioselective HPLC

Abstract The first example of the resolution of inherently chiral calix[8]arenes, 1,4-2,5-calix[8]bis-crown-4 1 and its methyl derivatives 2–4, has been achieved using enantioselective HPLC methods. The enantiomeric nature of isolated (+)-1 and (−)-1 was confirmed by CD spectra, specific optical rotation and 1H NMR in the presence of Pirkles reagent. A rationale is given for the observed HPLC enantioselectivity among compounds 2–4.

Direct chiral HPLC separation of the enantiomers of fluorinated N-arylamino-1-arylmethylphosphonate esters. Substituent effects on the enantioselectivity

Abstract Racemic N-arylamino-1-arylmethylphosphonic acid diethyl esters with various fluorinated substituents in one or both aryl rings have been resolved in their enantiomers by a direct HPLC method, using chiral stationary phases. The chiral separation on Chiralcel OD strongly depends on the substitution pattern in the N-aryl and/or in the C-aryl moieties and it improves markedly with the polarity of the fhiorinated substitnent. A new Pirkles chiral stationary phase (R)-α-Burke 1 is more efficient and in some cases more enantioselective than other Pirkles phases. A chiral recognition model between this phase and the enantiomers of an analyte afforded to propose the absolute configuration of the optical isomers and to relate it to the chiroptical behaviour.

Separation of the four pairs of enantiomers of vincamine alkaloids by enantioselective high-performance liquid chromatography.

The four enantiomeric pairs of vincamine group alkaloids were separated by HPLC using Chiralpak AD as chiral stationary phase (CSP) and various n-hexane-2-propanol and n-hexane-ethanol mobile phases. (+)-cis-Vincamine, which is used in pharmaceutical preparations, is eluted much faster than its optical isomer, with separation factors of 2.4 and 3.5, respectively in these mobile phases. Other CSPs gave negative results. A chiral recognition mechanism is proposed and circular dichroism spectra of the individual enantiomers are presented.

Resolution of inherently chiral resorcarene derivatives by enantioselective HPLC

Abstract The HPLC enantiomeric resolution of five inherently chiral tetrabenzoxazine derivatives of resorcarenes has been achieved by HPLC using Whelk-Ol and in one case Chiralpak AD as stationary phases. Enantiomeric separation was only observed in a very narrow range of mobile phase compositions. On-column enantiomeric interconversion of a racemic compound with a typical plateau-like elution profile was observed using a Chiralpak AD column

Separation of the enantiomers of anticonvulsant tricyclic pyrroloimidazolones by enantioselective HPLC. A chiral recognition model and a chiroptical study

Abstract The enantiomers of several pyrrolobenzimidazolone and pyrroloimidazopyridine derivatives have been successfully resolved by HPLC on a Whelk-O 1 Chiral Stationary Phase superior to other CSPs. A chiral recognition model explained the substituent effects on the enantioselectivity and afforded correlation of the elution order of the enantiomers to their absolute configuration. The exciton coupling method was applied to the CD spectra of the isolated enantiomers to confirm their absolute configuration.

Fluorenone 1,4-dihydropyridine derivatives with cardiodepressant activity: enantiomeric separation by chiral HPLC and conformational aspects.

The direct HPLC enantiomeric separation of five fluorenone-1,4-dihydropyridine-3,5-dicarboxylic diesters has been achieved using a Chiralpak AD stationary phase obtaining simultaneously good enantioselectivities, resolution factors, and elution times. CD spectra of the individual enantiomers for two compounds were measured. Thermodynamic parameters associated with the adsorption equilibria of the enantiomers with the chiral stationary phase were obtained from HLPC runs at various temperatures. The conformational preferences of the synperiplanar fluorenone group and of the cis/cis ester groups were obtained by 1H NMR spectra, including NOE experiments.

Liquid chromatographic separation of the enantiomers of antihistaminic 3,3′-di(1,3-thiazolidin-4-one) derivatives with two and four stereogenic centres

Abstract The enantiomers of anti-inflammatory and antihistaminic 3,3′-(1,2-ethanediyl)bis(2-aryl-1,3-thiazolidin-4-one) derivatives possessing two stereogenic centres were separated on Chiralcel OD stationary phase without derivatization. The meso form was also well separated from the enantiomers. The good resolution afforded a milligram-scale separation and subsequent measurement of the circular dichroism spectra of an enantiomeric pair. Addition of racemic α-mercaptopropionic acid to the N,N′-dibenzylideneethylenediamine yielded ten possible stereoisomers with four stereogenic centres. Two centres (2 and 2′) bear the same groups; the other two (5 and 5′) also bear the same groups, but these are different from the groups at 2 and 2′. In this situation four enantiomeric pairs and two meso forms exist; all of them were separated and identified using a Chiralpak AD column.

Resolution of the enantiomers of tetrahydrozoline by chiral HPLC. The racemization of the enantiomers via an imine–enamine tautomerism

Abstract Resolution of the enantiomers of the sympathomimetic drug tetrahydrozoline was obtained by chiral HPLC. The isolated enantiomers racemize easily and chiral HPLC experiments allowed the determination of the racemization rate constant. This process occurs via an imine–enamine tautomerism which was studied by UV and 1 H NMR spectroscopies.