Application of cyanuric chloride-based six new chiral derivatizing reagents having amino acids and amino acid amides as chiral auxiliaries for enantioresolution of proteinogenic amino acids by reversed-phase high-performance liquid chromatography

Biomedical Chromatography

2011

Self Cite

Enantioseparation of five β-blockers, namely, (R,S)-atenolol, (R,S)-propranolol, (R,S)-bisoprolol, (R,S)-metoprolol and (R,S)-carvedilol, was achieved as their diastereomers prepared with chiral derivatizing reagents (CDRs) synthesized on a cyanuric chloride platform. Fifteen CDRs were synthesized by nucleophilic substitution of the Cl atom in cyanuric chloride or its 6-methoxy derivative with amino acids (namely, L-Leu, L-Val, D-Phg, L-Met and L-Ala) or their amides as chiral auxiliaries. The diastereomers were synthesized under microwave irradiation for 70 or 100 s at 85% power. Separation of diastereomers was carried out on a C(18) column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid with UV detection at 230 nm. Separation efficiencies of the reagents were compared on the basis of effect of chiral auxiliaries (i.e. amino acids or amino acid amides) and achiral substituents (i.e. chlorine or methoxy group) in the CDRs. The method was validated for detection limit, linearity, accuracy and precision.

Section: Methodsmentioning

confidence: 99%

Enantioresolution of five β‐blockers by reversed‐phase high‐performance liquid chromatography using fifteen chiral derivatizing reagents having amino acids or their amides as chiral auxiliaries on a cyanuric chloride platform

Biomedical Chromatography

2011

Self Cite

“…Therefore, synthesis of new CDRs that can be (i) derived from cost‐effective and easily available structural moieties, (ii) prepared by using straightforward laboratory process and (iii) used for derivatization of analytes under mild conditions remains an area of great scientific interest. The literature reveals that CC (cyanuric chloride; 2,4,6‐trichloro‐1,3,5‐triazine; s ‐triazine chloride; trichloro‐ s ‐triazine) and DFDNB (1,5‐difluoro‐2,4‐dinitrobenzene) have evolved as excellent structural moieties to synthesize a wide spectrum of CDRs, for enantioresolution of analytes having different functional groups (Bhushan and Kumar, ; Bhushan and Martens, ; Ilisz et al , ; Brückner and Strecker, ; Brückner and Wachsmann ; Bhushan and Brückner ; Bhushan and Kumar, ; Bhushan and Tanwar, ; Bhushan and Dubey ; Bhushan and Dixit, –d).…”

Section: Introductionmentioning

confidence: 99%

“…Dichloro‐ s ‐triazine reagents (having amino acid amides as chiral auxiliaries) were found to be better CDRs in comparison to their MCT counterparts (having a methoxy group as achiral auxiliary) in terms of providing better resolution of diastereomers of α ‐amino acids (Bhushan and Kumar, ) and ( R , S )‐baclofen (Bhushan and Dixit, ). Subsequently, DCT reagents having amino acids as chiral auxiliaries were synthesized and used for enantioseparation of ( R , S )‐mexilitine (Bhushan and Dixit, ), α ‐amino acids (Bhushan and Dixit, ) and β ‐blockers (Bhushan and Dixit, ). These studies proved DCT reagents, having amino acids as chiral auxiliaries, to be more efficient in comparison to DCT reagents (having their amides as chiral auxiliaries) for providing better and faster resolution of resulting diastereomers.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HPLC enantioresolution of (R,S)‐baclofen using three newly synthesized dichloro‐s‐triazine reagents having amines and five others having amino acids as chiral auxiliaries

Biomedical Chromatography

2011

Self Cite

Enantioresolution of (R,S)-baclofen was accomplished using a newly synthesized set of three chiral derivatizing reagents (CDRs) having amines [(S)-(-)-α,4-dimethylbenzylamine, (-)-cis-myrtanylamine and (R)-(-)-1-cyclohexylethylamine] as chiral auxiliaries in cyanuric chloride and another set of five CDRs having amino acids (L-Leu, D-Phg, L-Val, L-Met and L-Ala) as chiral auxiliaries. These eight CDRs were used for synthesis of diastereomers of (R,S)-baclofen under microwave irradiation. The diastereomers were separated on a reversed-phase C(18) column using mixtures of methanol with aqueous trifluoroacetic acid with UV detection at 230 nm. Chromatographic data obtained for the two sets of diastereomers were compared among themselves and among the two groups. The method was validated for limit of detection, linearity, accuracy and precision.

“…Amino acids were found to be better chiral auxiliaries than amino acid amides in DFDNB-based CDRs for enantioresolution of a-amino acids [4] and b-amino alcohols [5], and also in cyanuric chloride (CC) based CDRs for enantioresolution of a-amino acids [11] and (R,S)-mexilitine [12]. The diastereomers prepared with the CDRs having amino acids as chiral auxiliaries were found to have higher resolutions and lower retention times.…”

Section: Introductionmentioning

confidence: 99%

Application of Hydrazino Dinitrophenyl-Amino Acids as Chiral Derivatizing Reagents for Liquid Chromatographic Enantioresolution of Carbonyl Compounds

2011

Chromatographia

Self Cite

A new series of chiral derivatizing reagents (CDRs) consisting of five hydrazino dinitrophenyl (HDNP)-amino acids (CDR 1-5) was prepared by a two-step synthesis procedure starting from 1,5-difluoro-2,4-dinitrobenzene (DFDNB). In the first step, five fluoro-dinitrophenyl (FDNP)-reagents, namely FDNP-L-Leu, FDNP-L-Val, FDNP-L-Phe, FDNP-L-Ala and FDNP-D-Phg were synthesized by substituting one of the fluorine atoms in DFDNB moiety with amino acids L-Leu, L-Val, L-Phe, L-Ala and D-Phg, respectively. In the following step, the remaining fluorine atom of the FDNP reagents was substituted with hydrazine hydrate to obtain five HDNP reagents (i.e. CDR 1-5; HDNP-L-Leu, HDNP-L-Val, HDNP-L-Phe, HDNP-LAla and HDNP-D-Phg). These five CDRs were used for synthesis of diastereomers of six racemic carbonyl compounds which were resolved by high-performance liquid chromatography using C18 column and gradient eluting mixture of acetonitrile or methanol with triethylammonium phosphate buffer with UV detection at 348 nm. Microwave irradiation was used for synthesis of both the CDRs and the diastereomers. The newly synthesized CDRs were observed to be superior in comparison to their counterparts having amino acid amides as chiral auxiliaries in terms of cost effectiveness and providing better resolution of diastereomers. The method was validated for limit of detection, linearity, accuracy and precision.