Whelk-01, stationary phase

The Whelk-01 was designed specifically for the separation of underivatized non-steroidal antiinflammatory drugs. The structure of the Whelk-01 stationary phase is given below. 

Fig. 5. The stmcture of the chiral selector in the Whelk-O-1 chiral stationary phase.

Pirkle and coworkers [59] compared retention and selectivity factors between HPLC and SFC using Poly Whelk-O chiral stationary phases and a-naphthyl-1-ethylamine carbamates. The results indicate that both retention and selectivity factors in SFC were higher than those in HPLC. This can be mainly attributed to the weaker solvating power of the carbon dioxide supercritical fluid as compared to a liquid such as methanol or hexane. 

Silica-base stationary phases have also been employed for enantiomeric separations in CEC [6,72-81]. In the initial work on chiral CEC, commercially available HPLC materials were utilized, including cyclodextrins [6,74,81] and protein-type selectors [73,75,80] such as human serum albumin [75] and ai-acid glycoprotein [73]. Fig. 4.9, for example, depicts the structure of a cyclodextrin-base stationary phase used in CEC and the separation of mephobarbital enantiomers by capillary LC and CEC in a capillary column packed with such a phase. The column operated in the CEC mode affords higher separation efficiency than in the capillary LC mode. Other enantiomeric selectors are also use in CEC, including the silica-linked or silica-coated macrocyclic antibiotics vancomycin [82,83] and teicoplanin [84], cyclodextrin-base polymer coated silicas [72,78], and weak anion-exchage type chiral phases [85]. Relatively high separation efficiency and excellent resolution for a variety of compounds have also been achieved using columns packed with naproxen-derived and Whelk-0 chiral stationary phases linked to 3 pm silica particles [79]. Fig. 4.10 shows the... 

Fig. 4.10. (A) The chiral stationary phases (S)-naproxen-derived and (3R,4S)-Whelk 0 1. (B) CEC enantiomeric separation of an antidepressant (N-[l-(4-bromo-phenyl)-ethyl]-2,2-dimethyl-propionamide) on a column packed with (3R,4S)-Whelk-0 1 chiral phase immobilized on 3 pm silica. Adapted from ref. [79] with permission. Copyright Elsevier 1997.

Fig. 9.10. Enantiomer separation on a 29.5 cm (overall length, 38 cm) capillary packed with (3R, -/S)-Whelk-0-stationary phase by CEC under slight overpressure (10 bar). Conditions MES (25 mM, pH 6.0)-acetonitrile (1 3.5, v/v) 25 kV UV detection, 230 nm. Reproduced from [48], with permission.

Figure 6.29 (a) molecular model of the chiral tweezers 6.53, (b) the chiral guest that forms part of the 7T-acidic stationary phase, a (3/ ,45 ) Whelk-0 1 silica-based chromatography column. 

Hi) n-electron acceptor/yc-electron donor stationary phases l-(3,5-Dinitrobenzamido)-l,2,3,4-tetrahydrophenanthrene W-(3,5-Dinitrobenzoyl)-l,2-diphenyl-1.2-diaminoethane yV-(3,5-Dinitrobenzoyl)-l,2-diaminocyclohexane yV-(3,5-DinitrobenzoyI)-(l-naphthyl)glycine amide Whelk-O 1 ULMO DACH DNB CHIREX 3005... 

Figure 10.8. Synthetic low-mass chiral stationary phases. (A) DNP-phenylglycine (B) ChyRoSine-A (C) P-GEM 1 (D) Whelk-0 I and (E) ULMO.

In order to broaden the capabilities of the Pirkle concept, both polar and polarizable groups were introduced into the molecule. The most popular of this type of chiral stationary phase are the (R,R) Whelk-01 and the (S,S)Whelk-01 phases, the structures of which are shown below. These phases are more versatile and have a wider field of application than the phases previously described. The phases are covalently bonded to the silica and so they can be used with almost any type of solvent. However, they have been found to operate most effectively in the normal phase mode. It should be noted that the polarizable character of the aromatic ring is essential for the stationary phase to function well. As the Pirkle phases are generally available in both the (R) and (S) configurations, the reversal of the elution order of a pair of enantiomers is possible. This stationary phase was originally designed for the separation of the Naproxen enantiomers but has found a wide application to the separation of epoxides, alcohols, diols, amides, imides and carbamates. 

Two of the more common Pirkle type stationary phases in use today are the a-Burke 1 and the Whelk-01. The structure of a-Burke 1 is given below. 

C. J. Welch, Anal54ical and Semi-Preparative Separation of Enantiomers Using Whelk-01 Chiral Stationary Phase Naproxen and Abscisic Acid as Case Studies, Chemistry in New Zealand, July 9 (1993). 

Zhang and Shamsi reported the combination of a chiral column tapered at the outlet end and coupled to ESI-MS for simultaneous analysis of ( )-warfarin and ( )-coumachIor [13]. The chiral CEC was performed in capillaries packed with 5.0 pm (3R, 4S)-Whelk-01 chiral stationary phase. AcetonitriIe/5 mM ammonium acetate (pH 4.0) (70 30, vA ) and methanoI/5 mM anuno-nium acetate (pH 8.5) (70 30, v/v) were used as mobile phase and sheath liquid, respectively. It was found that the externally tapered colunm showed much more reproducible retention time compared to the untapered colunm. However, because of the fragile outlet end of the external... 

Figure 4.14 Schematic illustration of the principles underlying design of Pirkle-type chiral stationary phases (CSPs). (a) Illustration of the concept of reciprocity a single enantiomer of a racemate which separates well on the CSP shown on the left, when used to produce a second CSP shown at the right, will usually afford separation of the enantiomers of analytes that are structurally similar to the chiral selector of the first CSP. Reproduced from Pirkle et al, J. Org. Chem. 57 (1992), 3854, Copyright (1992), with permission of the American Chemical Society, (b) Two CSPs that exhibit reciprocal behavior, and (c) enantiomeric recognition model for the more stable diastereomeric complex between (S)-naproxen dimethylamide and the Whelk-0-1 (3R,4R) analog. Note that hydrogen atoms bonded to carbons are omitted for clarity. Reproduced from Wolf and Pirkle (2002), Tetrahedron 58, 3597, copyright (2002), with permission from Elsevier.

Welch CJ, Szczerba T, Perrin SR. Some recent high-performance liquid chromatography separations of the enantiomers of pharmaceuticals and other compounds using the Whelk-Ol chiral stationary phase. J. Chromatogr. A 1997 758 93-98. 

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