Indirect resolution of enantiomers of penicillamine by TLC and HPLC using Marfey's reagent and its variants

Tanwar

2009

Twelve chiral derivatizing reagents (CDRs) were synthesized by substituting one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene (DFDNB) with three optically pure amines [(R)-(-)-1-cyclohexylethylamine, (+)-dehydroabietylamine and (S)-(-)-alpha,4-dimethylbenzylamine], six amino acid amides [L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg-NH(2)] and three amino acids [L-Ala, L-Val and L-Leu]. In addition, dinitrophenyl-L-Pro-N-hydroxysuccinimide ester and N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate were also synthesized and used as CDR. Keeping in view the presence of an amino group, diastereomers of six beta-blockers (atenolol, propranolol, bisoprolol, metoprolol, salbutamol, and carvedilol) were synthesized by reaction with these 14 CDRs. The diastereomers were separated by RP-HPLC. The method was validated for linearity, accuracy, limit of detection and limit of quantification.

Section: Introductionmentioning

confidence: 99%

Reversed‐phase high‐performance liquid chromatographic enantioresolution of six β‐blockers using dinitrophenyl‐l‐Pro‐N‐hydroxysuccinimide ester, N‐succinimidyl‐(S)‐2‐(6‐methoxynaphth‐2‐yl) propionate and twelve variants of Sanger's reagent as chiral derivatizing reagents

Tanwar

2009

“…Thus, a change in pH changes the ionic states of the chiral selector(s) and the isomers of PenA, resulting in non-interaction among the ionizable groups tion, simply based on solubility difference in the enantiomer and the chiral selector. The development required 10 min as compared with 40 min of development time for the diastereomers in an indirect method (Bhushan et al, 2007). The chiral selectors used in this direct method are easily available and inexpensive.…”

Section: Effect Of Temperature and Phmentioning

confidence: 99%

“…The literature reveals only a few TLC reports on enantiomeric resolution of PenA. These include ligand exchange resolution via ChiralPlate ® (Martens et al, 1986) in the form of DL-5,5-dimethyl-4-thiazolidinecarboxylic acid, obtained by its cyclization with HCHO (and the cyclic derivative was also used to determine the enantiomeric purity of pharmaceutical D-PenA by ligand exchange HPLC; Busker et al, 1985), and in the form of its diastereomers prepared with Marfey's reagent and two of its structural variants (Bhushan et al, 2007) using both normal-phase and reversed-phase TLC (and also RP-HPLC). L-Tartaric acid has previously been used in this laboratory as a chiral impregnating reagent for direct TLC enantiomeric resolution of phenylthiohydantoin (PTH) derivatives of amino acids (Bhushan and Ali, 1987), racemic ephedrine and atropine (Bhushan et al, 2001), and racemic atenolol and propranolol (Bhushan and Tanwar, 2008).…”

Section: Introductionmentioning

confidence: 99%

Direct enantiomeric TLC resolution of dl‐penicillamine using (R)‐mandelic acid and l‐tartaric acid as chiral impregnating reagents and as chiral mobile phase additive

Agarwal

2008

DL-Penicillamine has been resolved into its enantiomers by normal-phase TLC using L-tartaric acid as chiral impregnating reagent as well as chiral mobile phase additive, while (R)-mandelic acid has been found to be successful as a chiral impregnating reagent. The solvent system acetonitrile-methanol-water (5:1:1, v/v) was found to be successful when L-tartaric acid was used as impregnating agent while the solvent combination acetonitrile-methanol-(0.5% l-tartaric acid in water, pH 5)-glacial acetic acid (7:1:1.1:0.7, v/v) was successful as mobile phase as it contained L-tartaric acid as the chiral additive. (R)-mandelic acid was successful as chiral impregnating reagent with ethyl acetate-methanol-water (3:1:1, v/v), as the mobile phase. The effects of concentration of chiral selectors, temperature and pH were examined on enantiomeric resolution. The spots were detected with iodine vapors and the detection limits were found to be 0.12 microg for each enantiomer of penicillamine with L-tartaric acid, under both the conditions, and 0.11 microg with (R)-mandelic acid.

“…A TLC method was developed (Bhushan et al, 2007) for indirect chiral separation of penicillamine enantiomers after derivatization with Marfey's reagent (MR, FDNP-Ala-NH 2 ) and two of its structural variants, FDNP-Phe-NH 2 and FDNP-Val-NH 2 . The binary mobile phase of phenol-water (3 : 1 v/v) and solvent combinations of acetonitrile and triethylamine phosphate (TEAP) buff er were found to give the best separation in normal and reversed-phase TLC, respectively.…”

Section: Indirect Resolution Using Marfey's Reagent and Its Variantsmentioning

confidence: 99%

Enantioresolution of dl‐penicillamine

Kumar

2009

Penicillamine (PenA) is a nonproteinogenic amino acid containing a thiol group. The three functional groups in penicillamine undergo characteristic chemical reactions and differ in their ability to participate in various chemical and biochemical reactions. d-penicillamine is more active pharmacologically, while the l-isomer occurs 'naturally'. This review deals with the enantioresolution of PenA both by direct and indirect methods using liquid chromatography. HPLC separation of its diastereomers prepared with different chiral derivatizing reagents (on reversed-phase columns) and separation of the derivatives prepared with achiral reagents (on chiral columns or via ligand exchange mode) has been discussed. Separation of enantiomers tagged with achiral reagent (to add a chromophore for ehanced detection) when there is no diastereomer formation has been considered separately. In addition, application of PenA and its derivatives as chiral selector for enentioresolution of certain other compounds has also been discussed.