Early developments |
1966 |
Gil-Av et al. |
resolution by gas chromatography using amino acid derivatives as chiral selector |
1111 Gil-Av, E.; Feibush, B.; Charles-Sigler, R.; Tetrahedron Lett.
1966, 1009; Feibush, B.; Balan, A.; Altman, B.; Gil-Av, E.; J. Chem. Soc., Perkin Trans. 2
1979, 1230; Gil-Av, E.; J. Mol. Evol.
1975, 6, 131; Hare, P. E.; Gil-Av, E.; Science
1979, 204, 1226; Schurig, V.; Isr. J. Chem.
2016, 56, 890.
|
natural amino acids |
first baseline analytical resolution by gas chromatography |
1971 |
Rogozhin and Davankov |
first CSP (based on proline derivative and divinylbenzene polymer support) for LC enantiomer separation by enantioselective ligand exchange |
3434 Rogozhin, S. V.; Davankov, V. A.; Chem. Commun.
1971, 490; Davankov, V. A.; Bochkov, A. S.; Kurganov, A. A.; Roumeliotis, P.; Unger, K. K.; Chromatographia
1980, 13, 677; Yamskov, I. A.; Berezin, B. B.; Davankov, V. A.; Zolotarev, Y. A.; Dostavalov, I. N.; Myasoedov, N. F.; J. Chromatogr.
1981, 217, 539; Gübitz, G.; Juffmann, F.; Jellenz, W.; Chromatographia
1982, 16, 103; Brückner, H.; Chromatographia
1987, 24, 725; Veigl, E.; Lindner, W.; J. Chromatogr. A
1994, 660, 255; Grobuschek, N.; Schmid, M. G.; Tuscher, C.; Ivanova, M.; Gübitz, G.; J. Pharm. Biomed. Anal.
2002, 27, 599.
|
amino acids |
first baseline resolution by LC |
1973 |
Hesse and Hagel |
first polysaccharide-based enantiomer separation on microcrystalline cellulose triacetate |
3535 Hesse, G.; Hagel, R.; Chromatographia
1973, 6, 277.
|
Tröger's base |
this achievement led to the observation that the secondary structure of the natural polymer was crucial for the sorption of the analyte |
1973 |
Stewart and Doherty |
CSP based on proteins: enantiomer separation on bovine serum albumin bound to sepharose |
3636 Stewart, K. K.; Doherty, R. F.; Proc. Natl. Acad. Sci. U. S. A.
1973, 70, 2850.
|
tryptophan |
complete resolution of DL-tryptophan was accomplished when chromatographed on bovine-serum albumin-succinoyl-aminoethyl-sepharose |
1974 |
Blaschke |
resolution using optically active polyacrylamides |
3737 Blaschke, G.; Chem. Ber.
1974, 107, 237.
|
mandelic acid and ephedrine derivatives |
the recognition ability of these polymers depends on the employed synthetic methods since the chiral recognition sites within the CSPs must be formed during the polymerization process. |
the polymers exhibited a remarkably higher chiral recognition when prepared by the radical polymerization of optically active monomers in comparison to those prepared by the reaction of poly(acryloyl chloride) with the corresponding chiral amines. It has been found that the tacticity of polymethacrylamides influenced their chiral recognition abilities55 Allenmark, S.; Schurig, V.; J. Mater. Chem.
1997, 7, 1955; Okamoto, Y.; Ikai, T.; Chem. Soc. Rev.
2008, 37, 2593; Ward, T. J.; Ward, K. D.; Anal. Chem.
2010, 82, 4712; Cavazzini, A.; Pasti, L.; Massi, A.; Marchetti, N.; Dondi, F.; Anal. Chim. Acta
2011, 706, 205.,2424 Sellergren, B.; J. Chromatogr. A
2001, 906, 227; Yamamoto, C.; Okamoto, Y.; Bull. Chem. Soc. Jpn.
2004, 77, 227; Marty, J. D.; Mauzac, M.; Adv. Polym. Sci.
2005, 172, 1; Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O’Mahony, J.; Whitcombe, M. J.; J. Mol. Recognit.
2006, 19, 106; Shen, J.; Okamoto, Y.; Chem. Rev.
2016, 116, 1094; Morioka, K.; Suito, Y.; Isobe, Y.; Habaue, S.; Okamoto, Y.; J. Polym. Sci., Part A: Polym. Chem.
2003, 41, 3354.
|
1975 |
Cram and co-workers |
chiral crown ethers [bis(dinaphthyl)-22-crown-6] coated and covalently immobilized on silica gel for amino-acid esters |
3838 Dotsevi, G.; Sogah, Y.; Cram, D. J.; J. Am. Chem. Soc.
1975, 97, 1259; Sousa, L. R.; Sogah, G. D. Y.; Hoffman, D. H.; Cram, D. J.; J. Am. Chem. Soc.
1978, 100, 4569; Sogah, G. D. Y.; Cram, D. J.; J. Am. Chem. Soc.
1979, 101, 3035; Hyun, M. H.; Han, S. C.; Lipshutz, B. H.; Shin, Y.-J.; Welch, C. J.; J. Chromatogr. A
2001, 910, 359; Hyun, M. H.; Han, S. C.; Lipshutz, B. H.; Shin, Y.-J.; Welch, C. J.; J. Chromatogr. A
2002, 959, 75; Hyun, M. H.; Tan, G.; Cho, Y. J.; Biomed. Chromatogr.
2005, 19, 208.
|
natural or unnatural α-amino acids (or their esters) |
chiral selectors capable of resolving compounds bearing a primary amino functionality |
1976 |
Gil-Av and co-workers |
first donor-acceptor type CSP (later known as Pirkle concept) based on oxime derivatives of lactic acid and analogues of it |
3939 Mikeš, F.; Boshart, G.; Gil-Av, E.; J. Chromatogr.
1976, 122, 205.
|
helicenes |
coated and bonded chiral charge-transfer complexing agents as stationary phases |
1979 |
Pirkle et al. |
first Pirkle CSP, based on 2,2,2-trifluoro-1-(9-anthryl)ethanol-bonded selector |
4040 Pirkle, W. H.; House, D. W.; J. Org. Chem.
1979, 44, 1957; Pirkle, W. H.; House, D. W.; Finn, J. M.; J. Chromatogr.
1980, 192, 143.
|
chiral sulfoxides, 3,5-dinitrobenzoyl derivatives of amines, alcohols, thiols, amino acids, amino alcohols and hydroxy acids |
small molecules with groups acting as donors or receptors of p electrons leading to the formation of π-π charge transfer (face to face or face to edge) diastereomeric complexes with a specific enantiomer. Greater uniformity in distribution of chiral selectors upon the inert matrix, amplified enantio-recognition via effective steric barriers from structurally rigid fragments being part of these selectors, tailor-made molecular design for specific analytes, mobile or reverse phases allowed, mechanical stability, chemical inertness, capacity to separate high sample loading and an exceptionally good accessibility to chiral selectors with different features in both enantiomeric forms |
Pirkle CSP based on N-(3,5-dinitrobenzoyl)-phenylglycine |
3131 Pirkle, W. H.; Welch, C. J.; Hyun, M. H.; J. Org. Chem.
1983, 48, 5022; Pirkle, W. H.; Welch, C. J.; J. Org. Chem.
1984, 49, 138; Pirkle, W. H.; Welch, C. J.; Mahler, G. S.; J. Org. Chem.
1984, 49, 2504.
,
4141 Pirkle, W. H.; Finn, J. M.; J. Org. Chem.
1981, 46, 2935; Pirkle, W. H.; Schreiner, J. L.; J. Org. Chem.
1981, 46, 4988; Pirkle, W. H.; Finn, J. M.; Schreiner, J. L.; Hamper, B. C.; J. Am. Chem. Soc.
1981, 103, 3964.
|
N-acyl-1-arylaminoalkanes; piperidines and polyhydro-isoquinolines; chiral secondary arylalkyl-carbinols; derivatives of BINOL; hydantoins and succinimides |
Landmark papers that have led to modern (silica-based) CSPs and commercial columns |
1984 |
Hermansson |
α1-acid glycoprotein-bonded CSP (Chiralpak AGP) |
4242 Hermansson, J.; J. Chromatogr.
1984, 298, 67.
|
twelve racemic drug substances from different pharmacological groups (e.g. tropicamide, mepivacaine, mepensolate bromide) |
α1-AGP stationary phase proved to be highly stable since no tendency for degradation of the solid phase or denaturation of protein could be observed after daily use during prolonged period |
Landmark papers that have led to modern (silica-based) CSPs and commercial columns |
1984 |
Okamoto et al. |
polysaccharide CSPs obtained by coating of cellulose and amylose esters and carbamates onto the surface of macroporous silica particles |
4343 Okamoto, Y.; Kawashima, M.; Hatada, K.; J. Am. Chem. Soc.
1984, 106, 5357; Okamoto, Y.; Kawashima, M.; Yamamoto, K.; Hatada, K.; Chem. Lett.
1984, 739; Okamoto, Y.; Kawashima, M.; Hatada, K.; J. Chromatogr.
1986, 363, 173; Ichida, A.; Shibata, T.; Okamoto, Y.; Yuki, Y.; Namikoshi, H.; Toga, Y.; Chromatographia
1984, 19, 280; Shibata, T.; Okamoto, Y.; Ishii, K.; J. Liq. Chromatogr.
1986, 9, 313; Okamoto, Y.; Yashima, E.; Angew. Chem., Int. Ed.
1998, 37, 1020; Kubota, T.; Yamamoto, C.; Okamoto, Y.; J. Am. Chem. Soc.
2000, 122, 4056.
|
Pirkle's alcohol, Tröger's base; acrylates and methacrylates, anticholinergic drugs, miscellaneous compounds |
the grooves-shaped asymmetric structure characteristic of polysaccharide polymers allows the adsorption of enantiomers via inclusion mechanism. Cellulose triacetate and tribenzoate coated onto aminopropyl-silanised macroporous silica gel exhibited enhanced mass transfer and substantial mechanical stability |
1984 |
Allenmark et al. |
immobilized bovine serum albumin as a chiral stationary phase (Resolvosil, Chiralpak human serum albumin (HSA)) |
4444 Allenmark, S.; Bomgren, B.; Borén, H.; J. Chromatogr.
1984, 617.
|
N-acylated α-amino acids, benzoin |
immobilized protein as CSP using aqueous buffer systems as eluents |
1986 |
Armstrong et al. |
β-cyclodextrin-bonded CSP (Cyclobond I and others) |
4545 Armstrong, D. W.; Ward, T. J.; Armstrong, R. D.; Beesly, T. E.; Science
1986, 232, 1132.
|
diverse enantiomeric drugs: β-adrenergic blockers, antihistamine, sedative anticonvulsants (barbitals), central nervous system stimulant, cinchona alkaloids, antiestrogens, among others |
separation of stereoisomers of diverse drugs by the formation of β-cyclodextrin inclusion complexes |
1992 |
Pirkle et al. |
Donor-acceptor CSP with π-acidic and π-basic aromatic moieties (Whelk O1) |
3030 Pirkle, W. H.; Welch, C. J.; Burke, J. A.; Lamm, B.; Anal. Proc.
1992, 29, 225; Pirkle, W. H.; Welch, C. J.; Lamm, B.; J. Org. Chem.
1992, 57, 3854; Pirkle, W. H.; Liu, Y.; J. Chromatogr. A
1996, 736, 31; ibid. 749, 19; Pirkle, W. H.; Welch, C. J.; J. Chromatogr. A
1994, 683, 347.
,
4646 Pirkle, W. H.; Lee, W.; Bull. Korean Chem. Soc.
1998, 19, 1277; Pirkle, W. H.; Welch, C. J.; Tetrahedron: Asymmetry
1994, 5, 777; Pirkle, W. H.; Spence, P. L.; Chirality
1998, 10, 430; Pirkle, W. H.; Spence, P. L.; J. Chromatogr. A
1997, 775, 81; Yu, J. J.; Hyun, M. H.; Armstrong, D. W.; Breitbach, Z. S.; Ryoo, J. J.; Bull. Korean Chem. Soc.
2015, 36, 723.
|
profens; N-Boc or N-Cbz α-amino acids; α-aryloxy propionic acids, primary and secondary alcohols, diols, α-hydroxy ketones, α-substituted cyclohexanones, oxiranes, aziridines; phthalides, lactams, γ-lactones; oxazolidinones |
the discriminating ability of this class of selector has been attributed to a "pre-organized" cleft which provides an active site in which but one enantiomer of a profen could undergo simultaneous hydrogen bonding, π-π face-to-face stacking, and π-π face-to-edge interaction while in a relatively low energy conformation |
1994 |
Armstrong et al. |
macrocyclic-antibiotic-based CSPs (Chirobiotic V, T, TAG, R). |
2929 Berthod, A.; Chen, X.; Kullman, J. P.; Armstrong, D. W.; Gasparrini, F.; D’Acquarica, I.; Villani, C.; Carotti, A.; Anal. Chem.
2000, 72, 1767; Péter, A.; Árki, A.; Tourwé, D.; Forró, E.; Fülöp, F.; Armstrong, D. W.; J. Chromatogr. A
2004, 1031, 159; Pataj, Z.; Berkecz, R.; Ilisz, I.; Misicka, A.; Tymecka, D.; Fülöp, F.; Armstrong, D. W.; Péter, A.; Chirality
2009, 21, 787.
,
4747 Armstrong, D. W.; Tang, Y.; Chen, S.; Zhou, Y.; Bagwill, C.; Chen, J.-R.; Anal. Chem.
1994, 66, 1473; Berthod, A.; Chirality
2009, 21, 167; Péter, A.; Árki, A.;Vékes, E.; Tourwé, D.; Lázár, L.; Fülöp, F.; Armstrong, D. W.; J. Chromatogr. A
2004, 1031, 171; Pataj, Z.; Ilisz, I.; Berkecz, R.; Misicka, A.; Tymecka, D.; Fülöp, F.; Armstrong, D. W.; Péter, A.; J. Sep. Sci.
2008, 31, 3688; D’Acquarica, I.; Gasparrini, F.; Misiti, D.; Zappia, G.; Cimarelli, C.; Palmieri, G.; Carotti, A.; Cellamare, S.; Villani, C.; Tetrahedron: Asymmetry
2000, 11, 2375; Ilisz, I.; Grecsó, N.; Forró, E.; Fülöp, F.; Armstrong, D. W.; Péter, A.; J. Pharm. Biomed. Anal.
2015, 114, 312.
|
warfarin, proglumide, bendroflumethiazide; amino acids (free, N-acylated or O-methylated); ChirobioticTM TAG: common α-amino acids and other carboxylic acids; ChirobioticTM T: atenolol and pindolol (β-blockers); uncommon analogues of phenylalanine; β-amino acids |
macrocycles are functionally diversified, possessing many stereogenic centers, so the chiral recognition might be carried through different mechanisms including π-π complexation, hydrogen bonding, hydrophobic pocket, dipole stacking, steric interactions, or their combinations2020 Ilisz, I.; Pataj, Z.; Aranyi, A.; Péter, A.; Sep. Purif. Rev.
2012, 41, 207; Ilisz, I.; Berkecz, R.; Péter, A.; J. Chromatogr. A
2009, 1216, 1845; Ilisz, I.; Berkecz, R.; Péter, A.; J. Sep. Sci.
2006, 29, 1305.
|
V: vancomycin; T: teicoplanin; TAG: teicoplanin aglycone; R: ristocetin A |
CSPs based on macrocyclic antibiotics could be used in both normal and reversed mobile phases (multimodal selectors) |
1996 |
Lämmerhofer and Lindner |
quinine-carbamate-based CSPs (Chiralpak QN-AX) |
4848 Lämmerhofer, M.; Lindner, W.; J. Chromatogr. A
1996, 741, 33.
|
N-protected Phe derivatives; other chiral carboxylic acids |
these chiral selectors immobilized onto porous silica have preferentially operated with buffered aqueous mobile phases to resolve enantiomers of acidic analytes, involving ion pair mechanisms as the dominating binding interaction |
1996 |
Francotte |
immobilized polysaccharide CSPs (Chiralpak IA, IB, IC, etc.) |
4949 Francotte, E.; WO1996027615 A1
1996.
|
initially, optically active compounds usually employed as standards to test CSP were resolved: benzoin, Tröger's base, trans-stilbene oxide, benzodiazepines, etc. |
photochemically cross-linked polysaccharide derivatives in which the OH groups have been esterified as OR' groups or converted into a carbamate. The use of CH2Cl2 or THF is allowed since covalent binding avoids the sweeping observed for polysaccharides only physically adsorbed |
1998 |
Machida et al. Hyun et al. |
covalently bonded 18-crown-6-tetracarboxylic-acid-based CSP (ChiroSil) |
5050 Machida, Y.; Nishi, H.; Nakamura, K.; Nakai, H.; Sato, T.; J. Chromatogr. A
1998, 805, 85; Hyun, M. H.; Jin, J. S.; Lee, W.; J. Chromatogr. A
1998, 822, 155; Park, J. Y.; Jin, K. B.; Hyun, M. H.; Chirality
2012, 24, 427; Jin, K. B.; Kim, H. E.; Hyun, M. H.; Chirality
2014, 26, 272; Ahn, S. A.; Hyun, M. H.; Chirality
2015, 27, 268; Hyun, M. H.; Kim, D. H.; Chirality
2004, 16, 294; Hyun, M. H.; Cho, Y. J.; Kim, J. A.; Jin, J. S.; J. Liq. Chromatogr. Relat. Technol.
2003, 26, 1083; Hyun, M. H.; Song, Y.; Choo, Y. J.; Choi, H. J.; Chirality
2008, 20, 325; Hyun, M. H.; Song, Y.; Choo, Y. J.; Choi, H. J.; J. Sep. Sci.
2007, 30, 2539; Berkecz, R.; Ilisz, I.; Misicka, A.; Tymecka, D.; Fülöp, F.; Choi, H. J.; Hyun, M. H.; Péter, A.; J. Sep. Sci.
2009, 32, 981; Ilisz, I.; Pataj, Z.; Berkecz, R.; Misicka, A.; Tymecka, D.; Fülöp, F.; Choi, H. J.; Hyun, M. H.; Péter, A.; J. Chromatogr. A
2010, 1217, 1075.
|
amines, α-amino acids, aand β-amino acids, α-amino amides, aryl α-amino ketones, primary amines and amino alcohols |
tetracarboxylic-acid-derived crown ether chiral selectors have proved being successful for the resolution of various primary amino compounds with the use of aqueous mobile phases containing organic and acidic modifiers |
chiral drugs: benzodiazepinones, mexiletine analogues, amino esters of acyclovir, β-blockers |
β2- and β3-homo-amino acids |
2008 |
Lindner and co-workers |
zwitterionic quinine-carbamate-based CSPs (Chiralpak ZWIX) |
5151 Hoffmann, C. V.; Pell, R.; Lämmerhofer, M.; Lindner, W.; Anal. Chem.
2008, 80, 8780; Keunchkarian, S.; Osorio Grisales, J.; Padró, J. M.; Boeris, S.; Castells, C. B.; Chirality
2012, 24, 512; Sardella, R.; Lämmerhofer, M.; Natalini, B.; Lindner, W.; Chirality
2008, 20, 571.
|
β -blockers, N-protected natural a-amino acids, free natural and unnatural a-amino acids with pharmaceutical activity, β-amino acids |
ion exchanger type chiral stationary phases based on zwitterionic selectors. These selectors interact with ionizable analytes via ionic interactions, but π-πinteractions and hydrogen bonding contribute to the stabilization of the complex |
2009 |
Armstrong and co-workers |
cyclofructan-based CSPs (Larich series) |
5252 Sun, P.; Wang, C.; Breitbach, Z. S.; Zhang, Y.; Armstrong, D. W.; Anal. Chem.
2009, 81, 10215.
|
trans-1-amino-2-indanol, Tröger's base, orphenadrine citrate salt, N-(3,5-dinitrobenzoyl)-DL-leucine, thalidomide, among others |
aliphatic functionalized cyclofructans possess unique enantiomeric selectivities to separate a broad range of racemic compounds, it is possible to modulate the affinity of cyclofructans by partially derivatizing the hydroxyl groups therefore disrupting internal hydrogen bonding |
α -aryl ketones1919 Breitbach, A. S.; Lim, Y.; Xu, Q.-L.; Kürti, L.; Armstrong, D. W.; Breitbach, Z. S.; J. Chromatogr. A
2016, 1427, 45.
|