Pirkle phases preparation

There is a wide variety of commercially available chiral stationary phases and mobile phase additives.32 34 Preparative scale separations have been performed on the gram scale.32 Many stationary phases are based on chiral polymers such as cellulose or methacrylate, proteins such as human serum albumin or acid glycoprotein, Pirkle-type phases (often based on amino acids), or cyclodextrins. A typical application of a Pirkle phase column was the use of a N-(3,5-dinitrobenzyl)-a-amino phosphonate to synthesize several functionalized chiral stationary phases to separate enantiomers of... 

Mechanistic considerations (e.g., the extensive work published on brush-type phases) or the practitioner s experience might help to select a chiral stationary phase (CSP) for initial work. Scouting for the best CSP/mobile phase combination can be automated by using automated solvent and column switching. More than 100 different CSPs have been reported in the literature to date. Stationary phases for chiral pSFC have been prepared from the chiral pool by modifying small molecules, like amino acids or alkaloids, by the deriva-tization of polymers such as carbohydrates, or by bonding of macrocycles. Also, synthetic selectors such as the brush-type ( Pirkle ) phases, helical poly(meth) acrylates, polysiloxanes and polysiloxane copolymers, and chiral selectors physically coated onto graphite surfaces have been used as stationary phases. 

W. H. Pirkle and B. C. Hamper, The direct preparative resolution of enantiomers by liquid chromatography on chiral stationary phases in Preparative Liquid Chromatography, B. A. Bidling-meyer (Ed.), Journal Chromatography Library Vol. 38, 3 Edition, Elsevier Science Publishers B. V, Amsterdam (1991) Chapter 7. 

Small chiral molecules. These CSPs were introduced by Pirkle about two decades ago [31, 32]. The original brush -phases included selectors that contained a chiral amino acid moiety carrying aromatic 7t-electron acceptor or tt-electron donor functionality attached to porous silica beads. In addition to the amino acids, a large variety of other chiral scaffolds such as 1,2-disubstituted cyclohexanes [33] and cinchona alkaloids [34] have also been used for the preparation of various brush CSPs. 

Initially, chiral stationary phases for chiral liquid chromatography were designed for preparative purposes, mostly based on the concept of three-point recognition .47 Pirkle and other scientists48 developed a series of chiral stationary phases that usually contain an aryl-substituted chiral compound connected to silica gel through a spacer. Figure 1-14 depicts the general concept and an actual example of such a chiral stationary phase. 

The Pirkle-type chiral stationary phases are quite stable and exhibit good chiral selectivities to a wide range of solute types. These CSPs are also popular for the separation of many drug enantiomers and for amino acid analysis. Primarily, direct chiral resolution of racemic compounds were achieved on these CSPs. However, in some cases, prederivatization of racemic compounds with achiral reagents is required. The applications of these phases are discussed considering re-acidic, re-basic, and re-acidic-basic types of CSP. These CSPs have also been found effective for the chiral resolution on a preparative scale. Generally, the normal phase mode was used for the chiral resolution on these phases. However, with the development of new and more stable phases, the reversed phase mode became popular. 

The enantiomeric excess of this product was determined to be >99.5X using a chiral stationary phase HPLC (preparative Regis Pirkle Type 1-A, 10 x 250 tm I.D., 7.5 mt/min flow rate, 1000 psi pressure, lOX 2-propanol in hexane, detector at 284 nm). The R-(-)-enant1omer Is eluted first and the peaks are well separated. Another batch of phosphate ([ 3p -507.7 C, THF, e 1.17) was shown to have 96.5% ee using the same conditions. 

The brush-type of CSP was introduced by Pirkle who was one of the pioneers of modern enantioselective liquid chromatography [55]. The most frequently used 7i-acceptor phases are derived from the amino acids phenylglycine (DNBPG) (Fig. 6.8) or leucine (DNBLeu) covalently or ionically bonded to 3-aminopropyl silica gel [56, 57]. These CSPs are commercially available for analytical or preparative separation of enantiomers. Further CSPs based on amino acid or amine chiral selectors such as valine, phenylalanine, tyrosine [58] and l,2-tr s-diaminocyclohexane (DACH-DNB phase) [59] and 1,2-traus-diphenylethylene diamine (ULMO phase) [60] were also developed (Fig. 6.8). These CSPs have been applied for the preparative separation of the enantiomers of a few racemic compounds, but the number of reported preparative applications has remained very limited over the last 10 years. 

Blum AM, Lynam KG, Nicolas EC. Use of a new Pirkle-type chiral stationary phase in analytical and preparative subcritical fluid chromatography of pharmaceutical compounds. Chirality 1994 6 302-313. 

Pirkle, W.H. Pochapsky. T.C. Mahler, G.S. Corey. D.E. Reno. D.S. Alessi. D.M. Useful and easily prepared chiral stationary phases for the direct chromatographic separation of the enantiomers of a ariety of deriv atised amines, ammo... 

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