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

Abstract

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 as chiral auxiliaries in cyanuric chloride‐based chiral derivatizing agents for enantioseparation by liquid chromatography

“…Five β ‐blockers, namely, ( R , S )‐atenolol, ( R , S )‐propranolol, ( R , S )‐bisoprolol, ( R , S )‐metoprolol and ( R , S )‐carvedilol (shown in Fig. ), were investigated for their enantioseparation (Bhushan and Dixit, ) using the same set of DCT and MCT reagents mentioned in the section ‘Enantioseparation of ( R , S )‐baclofen’ (Bhushan and Dixit, , ).…”

“…In view of the different biological behaviors of the two enantiomers of ( R , S )‐baclofen, the need arises for the development of rapid and economic methods for their separation and control of enantiomeric purity. Bhushan and Dixit (, ) achieved successful enantioseparation of ( R , S )‐baclofen by an indirect method using 15 CDRs (Table ) having amino acids or their amides as chiral auxiliaries on CC moiety, as discussed briefly below.…”

Enantioresolution of (RS)‐baclofen by liquid chromatography: A review

“…Dichloro‐ s ‐triazine reagents (having amino acid amides as chiral auxiliaries) were found to provide better and faster resolution of diastereomeric derivatives of α ‐amino acids, ( RS )‐mexilitine and β ‐blockers (Bhushan & Kumar, ) in comparison to their MCT counterparts (having a methoxy group as achiral auxiliary). DCT reagents have also been successful in enantioseparation of ( RS )‐Bac.A total of 12 DCT reagents were synthesized in three sets based on the nature of the chiral auxiliary: three CDRs (CDR ‐8–10 ) having an optically pure amine [namely, ( S )‐(−)‐ α ,4‐dimethylbenzylamine, (−)‐ cis ‐myrtanylamine or ( R )‐(−)‐1‐cyclohexylethylamine] as the chiral auxiliary in CC (Bhushan & Dixit, ); five CDRs (CDR ‐11–15 ) having an amino acid (namely, l ‐Leu, d ‐Phg, l ‐Val, l ‐Met or l ‐Ala) as the chiral auxiliary (Bhushan & Dixit, ); and four CDRs (CDR ‐16–19 ) by incorporating an amino acid amide (namely, l ‐Leu‐NH 2 , d ‐Phg‐NH 2 , l ‐Val‐NH 2 or l ‐Ala‐NH 2 ) as the chiral auxiliary in trichloro‐ s ‐triazine (Bhushan & Dixit, ). …”

“…CDR‐ 8 – 10 , basic structure A; CDR‐ 11 – 19 , basic structure B. Reference: CDR‐ 8 – 15 , Bhushan & Dixit, ; CDR‐ 16 – 19 , Bhushan and Dixit ().…”

Synthesis of three strong UV-absorbing Naproxen-based chiral derivatizing agents and their application for enantioseparation of Baclofen by RP-HPLC

“…Also, the (R)-enantiomer is known to decrease the heart rate and arterial pressure, whereas the (S)-enantiomer has no effect on heart rate, on the contrary, it increases the arterial pressure [7]. [10] and CDRs based on cyanuric chloride [11,12] for derivatizing Bac for its enantioseparation by indirect approach using reversed phase HPLC.…”