Pirkle columns

The optical purity and stereochemistry was established by conversion to the known A-BOC protected proline and by comparison of spectral data and rotation values161. Additionally, the optical purity was established by HPLC analysis of the 3,5-dinitrobenzoates on a Pirkle column and by Mosher ester analysis. 

The absolute configuration of all chiral amines prepared was determined by comparison with literature rotation values to be S. The (S)-enantiomers possess a positive rotation and the derived a-naphthamides elute, as in other cases, after the (//(-enantiomer on a chiral Pirkle column. 

Many types of chiral stationary phase are available. Pirkle columns contain a silica support with bonded aminopropyl groups used to bind a derivative of D-phenyl-glycine. These phases are relatively unstable and the selectivity coefficient is close to one. More recently, chiral separations have been performed on optically active resins or cyclodextrins (oligosaccharides) bonded to silica gel through a small hydrocarbon chain linker (Fig. 3.11). These cyclodextrins possess an internal cavity that is hydro-phobic while the external part is hydrophilic. These molecules allow the selective inclusion of a great variety of compounds that can form diastereoisomers at the surface of the chiral phase leading to reversible complexes. 

Saline lloprost HPLC Derivatize with 1-naphthylisocynate, Cin, SPE Pirkle column MeOH-0.05% TFA-0.05% TEA 230 nm Resolved enantiomers [522]... 

C. L. Hsu and R. R. Walters, Chiral separation of ibutilide enantiomers by derivatization with 1-napthyl isocyanate and HPLC on a Pirkle column, J. Chromatogr., 550 621 (1991). 

Figure 5. The chromatographic resolution of (R,S)-IV on an ionic Pirkle column. Flow rate 1 ml/min. Eluant hexane/2-propanol, 60/40 (a), 80/20 (b), and 90/10 (c). Absorption (A) and CD detection ( ) at 254 nm. (From Ref. 21)...

Choosing a CSP. Exactly how a CSP works is not known, and the choice of a CSP for a particular separation has been mostly by trial and error. However, some of the principles of chiral recognition have been identified for the Pirkle columns. 

The optical purity of BINAP is analyzed after oxidizing to BINAPO by HPLC using a Pirkle column (Baker bond II) and a hexane/ethanol mixture as eluent. ... 

The checkers obtained first crops of 87% and 75.8%, mp 263-263.5 0, [a] 0 -389° (benzene, mother liquors of 11% and 13.5% respectively. These materials were analyzed on a Pirkle column (Baker bond II) with hexane/ethanol mixtures and found to have S/R ratios of 99.7/0.3 (first crop) and 93/1.7 (mother liquor). The submitters report obtaining analytically pure (S)-BINAPO by recrystallization from a mixture of hexane and toluene, mp 261-262 0, Coi]q -396° (benzene, o 0.467). 

The checkers had yields ranging from 69 to 90%. They determined the enantiomeric purity of the S-BINAPO component, -168° (ethanol, o 0.5), to be 99.6/0.4 using a Pirkle column (Note 16). The submitters report that recrystallization from a 1 2 mixture of ethyl acetate and chloroform gave an analytically pure sample, rap 240-241°C (dec), [ ]q -174° (ethanol, o 0.523). 

Brucine is used in a similar manner and the carboxyl unit of the amino acid is coordinated to the tertiary amine unit in brucine rather than the poorly basic amide nitrogen. Selective crystallization of these salts leads to their separation, and basic hydrolysis leads to an enantiopure amino acid. It is now possible to separate many racemic mixtures into their enantiomeric components by using high-pressure liquid chromatography (HPLC) fitted with a column that contains a chiral compound bound to an adsorbent (known as chiral HPLC columns). Such columns have been developed by William H. Pirkle (United States 1934-). The chiral HPLC column is prepared by coating a chiral chemical compound on an inert material when a solution of the racemic mixture passes through this column, one enantiomer is adsorbed to the column material better than the other. These are sometimes called Pirkle columns. 

Examples of the enantioselective stationary phases that have been developed for these purposes include both monomer coated columns [Pirkle columns (2), cyclodextrin columns (3), macrocyclic antibiotic columns (4), etc.] and polymer coated enantioselective stationary phases [polysaccharide (5,6), polyacrylamide (7)]. Although a thorough evaluation of all enantioselective columns is impossible, the commonly used ones do seem to have their limitations. It is fair to say that despite these advances, the chiral resolution of racemic materials remains a major challenge. Resolution of a racemic sample is still a time-consuming, trial-and-error approach, often requiring experimentation with many expensive enantioselective columns. Moreover, typical separation factors achieved are less than 1.5. 

Fig. 14 Representative direct enantiomeric separations of brivanib and its isomers on different CSPs (a) polysaccharide Chiralcel OD-H (coated ceUulose carbamate), (b) Chiralpak 1C (3,5-dichlorophenylcarbamate of cellulose, immobilized on 5-(jtm silica), (c) Chirobiotic V2 (vancomycin), (d) Cyclobond RSP (cyclodextrin), (e) ChiroSil SCA (-) (crown ether), and (f) Sumichiral OA-4800 (Pirkle) column. Peak identification 1, (SR)-, 2, (RS) 3, (RR)-, 4, (S5) 5, positional isomer , chemical impurity (adapted from [150])...

Pirkle column Named for its inventor, the original Pirkle column was a monomeric bonded phase that had the following structure This bonded phase and many others having similar construction are chiral in nature ( denotes the chiral center) and are used in the separation of enantiomers. 

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