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Chromatographia

, Volume 76, Issue 15–16, pp 871–897 | Cite as

Small Molecules as Chromatographic Tools for HPLC Enantiomeric Resolution: Pirkle-Type Chiral Stationary Phases Evolution

  • Carla Fernandes
  • Maria Elizabeth Tiritan
  • Madalena PintoEmail author
Review

Abstract

This review focuses on the evolution of Pirkle-type chiral stationary phases (CSPs), based on chiral recognition mechanism of small molecules and applications directly related with Medicinal Chemistry. Therefore, the strategies to plan these chiral selectors for enantioseparation of diverse therapeutic classes of chiral drugs and the understanding of the recognition mechanism are emphasized. The planning of Pirkle and co-workers to design different classes of CSPs was initially based on NMR studies, following the principle of reciprocity together with chromatographic results and studies of chiral recognition phenomena. All those features are described and critically discussed in this review. Finally, based on general principles established by Pirkle’s work it can be inferred that diverse chiral small molecules can be successfully used as chromatographic tools for enantiomeric resolution. In this context, several research groups were inspired on Pirkle’s design to develop new CSPs. Xanthone derivatives bonded to chiral groups were also exploited as selectors for CSPs and are briefly reported.

Keywords

HPLC Chiral stationary phase Chirality Chiral recognition Enantioresolution Xanthone derivatives 

Notes

Acknowledgments

FCT—Fundação para a Ciência e a Tecnologia under the project CEQUIMED-PEst-OE/SAU/UI4040/2011.

References

  1. 1.
    Caldwell J (1996) Importance of stereospecific bioanalytical monitoring in drug development. J Chromatogr A 719(1):3–13CrossRefGoogle Scholar
  2. 2.
    Triggle DJ (1997) Stereoselectivity of drug action. Drug Discovery Today 2(4):138–147CrossRefGoogle Scholar
  3. 3.
    Rentsch KM (2002) The importance of stereoselective determination of drugs in the clinical laboratory. J Biochem Biophys Methods 54(1–3):1–9CrossRefGoogle Scholar
  4. 4.
    Cordato DJ, Mather LE, Herkes GK (2003) Stereochemistry in clinical medicine: a neurological perspective. J Clin Neurosci 10(6):649–654CrossRefGoogle Scholar
  5. 5.
    Baumann P, Zullino DF, Eap CB (2002) Enantiomers’ potential in psychopharmacology—a critical analysis with special emphasis on the antidepressant escitalopram. Eur Neuropsychopharmacol 12(5):433–444CrossRefGoogle Scholar
  6. 6.
    Baker GB, Prior TI, Coutts RT (2002) Chirality and drugs used to treat psychiatric disorders. J Psychiatry Neurosci 27(6):401–403Google Scholar
  7. 7.
    Caldwell J (1995) Stereochemical determinants of the nature and consequences of drug metabolism. J Chromatogr A 694(1):39–48CrossRefGoogle Scholar
  8. 8.
    Brocks DR (2006) Drug disposition in three dimensions: an update on stereoselectivity in pharmacokinetics. Biopharm Drug Dispos 27(8):387–406CrossRefGoogle Scholar
  9. 9.
    Mannschreck A, Kiesswetter R, von Angerer E (2007) Unequal activities of enantiomers via biological receptors: examples of chiral drug, pesticide, and fragrance molecules. J Chem Educ 84(12):2012–2017CrossRefGoogle Scholar
  10. 10.
    Kasprzyk-Hordern B (2010) Pharmacologically active compounds in the environment and their chirality. Chem Soc Rev 39(11):4466–4503CrossRefGoogle Scholar
  11. 11.
    Pasteur L (1848) Memoire sur la relation qui peut exister entre la forme crystalline et la composition chimique et sur la cause del la polarization rotatoire. Competes rendues de l’ Academie des Sciences 26:535–538Google Scholar
  12. 12.
    Blaschke G et al (1979) Chromatographic separation of racemic thalidomide and teratogenic activity of its enantiomers (author’s transl). Chromatographische Racemattrennung von Thalidomid und teratogene Wirkung der Enantiomere. Arzneimittelforschung 29(10): 1640–1642Google Scholar
  13. 13.
    FDA (1992) FDA’s policy statement for the development of new stereoisomeric drugs. Fed Reg 57: FR 22249Google Scholar
  14. 14.
    Investigation of chiral active substances. Directive 75/318/EEC (1993)Google Scholar
  15. 15.
    Shimazawa R et al (2008) Present state of new chiral drug development and review in Japan. J Health Sci 54(1):23–29CrossRefGoogle Scholar
  16. 16.
    Maier NM, Franco P, Lindner W (2001) Separation of enantiomers: needs, challenges, perspectives. J Chromatogr A 906(1–2):3–33Google Scholar
  17. 17.
    Caner H et al (2004) Trends in the development of chiral drugs. Drug Discovery Today 9(3):105–110CrossRefGoogle Scholar
  18. 18.
    Agranat I, Wainschtein SR (2010) The strategy of enantiomer patents of drugs. Drug Discovery Today 15(5–6):163–170CrossRefGoogle Scholar
  19. 19.
    Metzger S et al (2005) Entfernung von iodierten Röntgenkontrastmitteln bei der kommunalen Abwasserbehandlung durch den Einsatz von Pulveraktivkohle. GWF Wasser Abwasser 9:638Google Scholar
  20. 20.
    http://www.imshealth.com. Accessed 6 Mar 2013
  21. 21.
    Agranat I, Caner H (1999) Intellectual property and chirality of drugs. Drug Discovery Today 4(7):313–321CrossRefGoogle Scholar
  22. 22.
    Hutt AJ, Valentová J (2003) The chiral switch: the development of single enantiomers drugs from racemates. Acta Facultatis Pharmaceuticae Universitatis Comenianae 50:7–23Google Scholar
  23. 23.
    Francotte ER (2001) Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. J Chromatogr A 906(1–2):379–397Google Scholar
  24. 24.
    Francotte E, Lindner W (2006) Methods and principles in medicinal chemistry: chirality in drug research, vol 33. Wiley, WeinheimCrossRefGoogle Scholar
  25. 25.
    Taylor DR, Maher K (1992) Chiral separations by high-performance liquid chromatography. J Chromatogr Sci 30(3):67CrossRefGoogle Scholar
  26. 26.
    Haginaka J (2002) Pharmaceutical and biomedical applications of enantioseparations using liquid chromatographic techniques. J Pharm Biomed Anal 27(3–4):357–372CrossRefGoogle Scholar
  27. 27.
    Toyo’oka T (2002) Resolution of chiral drugs by liquid chromatography based upon diastereomer formation with chiral derivatization reagents. J Biochem Biophys Methods 54(1–3):25–56CrossRefGoogle Scholar
  28. 28.
    Zhang Y et al (2005) Enantioselective chromatography in drug discovery. Drug Discovery Today 10(8):571–577CrossRefGoogle Scholar
  29. 29.
    Cavazzini A et al (2011) Recent applications in chiral high performance liquid chromatography: a review. Anal Chim Acta 706:205–222CrossRefGoogle Scholar
  30. 30.
    Lämmerhofer M (2010) Chiral recognition by enantioselective liquid chromatography: mechanisms and modern chiral stationary phases. J Chromatogr A 1217(6):814–856CrossRefGoogle Scholar
  31. 31.
    Kalíková K, Riesová M, Tesařová E (2012) Recent chiral selectors for separation in HPLC and CE. Cent Eur J Chem 10(3):450–471Google Scholar
  32. 32.
    Ward TJ, Ward KD (2012) Chiral separations: a review of current topics and trends. Anal Chem 84(2):626–635CrossRefGoogle Scholar
  33. 33.
    Okamoto Y, Ikai T (2008) Chiral HPLC for efficient resolution of enantiomers. Chem Soc Rev 37(12):2593–2608CrossRefGoogle Scholar
  34. 34.
    Felix G, Berthod A (2007) Commercial chiral stationary phases for the separations of clinical racemic drugs. Sep Purif Rev 36(4):285–481CrossRefGoogle Scholar
  35. 35.
    Pirkle WH, Pochapsky TC (1989) Considerations of chiral recognition relevant to the liquid chromatographic separation of enantiomers. Chem Rev 89(2):347–362CrossRefGoogle Scholar
  36. 36.
    Gorog S, Gazdag M (1994) Enantiomeric derivatization for biomedical chromatography. J Chromatogr B Biomed Appl 659(1–2):51–84CrossRefGoogle Scholar
  37. 37.
    Dalgliesh CE (1952) The optical resolution of aromatic amino-acids on paper chromatograms. J Chem Soc (resumed): 3916–3922Google Scholar
  38. 38.
    Davankov VA (1997) The nature of chiral recognition: is it a three-point interaction? Chirality 9(2):99–102CrossRefGoogle Scholar
  39. 39.
    Booth TD, Wahnon D, Wainer IW (1997) Is chiral recognition a three-point process? Chirality 9(2):96–98CrossRefGoogle Scholar
  40. 40.
    Kafri R, Lancet D (2004) Probability rule for chiral recognition. Chirality 16(6):369–378CrossRefGoogle Scholar
  41. 41.
    Lämmerhofer M (2010) Chiral recognition by enantioselective liquid chromatography: mechanisms and modern chiral stationary phases. J Chromatogr A 1217(6):814–856CrossRefGoogle Scholar
  42. 42.
    Scriba GKE (2012) Chiral recognition mechanisms in analytical separation sciences. Chromatographia 75(15–16):815–838CrossRefGoogle Scholar
  43. 43.
    Däppen R, Karfunkel HR, Leusen FJJ (1990) Computational chemistry applied to the design of chiral stationary phases for enantiomeric separation. J Comput Chem 11:181–193CrossRefGoogle Scholar
  44. 44.
    Weinstein S, Leiserowitz L, Gil-Av E (1980) Chiral secondary amides. 2. Molecular packing and chiral recognition. J Am Chem Soc 102(8):2768–2772CrossRefGoogle Scholar
  45. 45.
    Lipkowitz KB (2001) Atomistic modeling of enantioselection in chromatography. J Chromatogr A 906(1–2):417–442Google Scholar
  46. 46.
    Lipkowitz KB (1994) Theoretical studies of brush-type chiral stationary phases. J Chromatogr A 666(1–2):493–503Google Scholar
  47. 47.
    Lipkowitz KB, Baker B (1990) Computational analysis of chiral recognition in Pirkle phases. Anal Chem 62:770–774CrossRefGoogle Scholar
  48. 48.
    Busch KW, Busch MA (2006) Chiral analysis, 1st edn. Elsevier, OxfordGoogle Scholar
  49. 49.
    Pirkle WH, Däppen R (1987) Reciprocity in chiral recognition. Comparison of several chiral stationary phases. J Chromatogr A 404(C): 107–115Google Scholar
  50. 50.
    Welch CJ (1994) Evolution of chiral stationary phase design in the Pirkle laboratories. J Chromatogr A 666(1–2):3–26Google Scholar
  51. 51.
    Welch CJ (1995) Crawling out of the chiral pool: the evolution of Pirkle-type chiral stationary phases. In: Brown PR, Grushka E (eds) Advances in chromatography. Marcel Dekker, New York, p 171–197Google Scholar
  52. 52.
    Pirkle WH (1966) The nonequivalence of physical properties of enantiomers in optically active solvents. Differences in nuclear magnetic resonance spectra. I [20]. J Am Chem Soc 88(8):1837CrossRefGoogle Scholar
  53. 53.
    Pirkle WH, Beare SD (1967) Nonequivalence of the nuclear magnetic resonance spectra of enantiomers in optically active solvents. IV. Assignment of absolute configuration [25]. J Am Chem Soc 89(21):5485–5487CrossRefGoogle Scholar
  54. 54.
    Pirkle WH, Burlingame TG (1967) Nonequivalence of the nuclear magnetic reasonance spectra of enantiomers in optically active solvents III. Tetrahedron Lett 8(41):4039–4042CrossRefGoogle Scholar
  55. 55.
    Pirkle WH, Burlingame TG, Beare SD (1968) Optically active NMR solvents VI. The determination of optical purity and absolute configuration of amines. Tetrahedron Lett 9(56):5849–5852CrossRefGoogle Scholar
  56. 56.
    Pirkle WH, Beare SD, Muntz RL (1974) Assignment of absolute configuration of sulfoxides by NMR. A solvation model. Tetrahedron Lett 15(26):2295–2298CrossRefGoogle Scholar
  57. 57.
    Pirkle WH, Beare SD, Muntz RL (1969) Optically active solvents for nuclear magnetic resonance X. Enantiomeric nonequivalence of sulfinamides, sulfinates, sulfites, thiosulfinates, phosphine oxides, and amine oxides [18]. J Am Chem Soc 91(16):4575CrossRefGoogle Scholar
  58. 58.
    Pirkle WH, Hoekstra MS (1976) Chiral nuclear magnetic resonance solvating agents. Resolution, determination of enantiomeric purity, and assignment of absolute configuration of cyclic and acyclic sulfinate esters. J Am Chem Soc 98(7):1832–1839CrossRefGoogle Scholar
  59. 59.
    Pirkle WH, Muntz RL, Paul IC (1971) Chiral nuclear magnetic resonance solvents. XI. A method for determining the absolute configuration of chiral N, N-dialkylarylamine oxides [27]. J Am Chem Soc 93(11):2817–2819CrossRefGoogle Scholar
  60. 60.
    Pirkle WH, Beare SD (1969) Optically active solvents in nuclear magnetic resonance spectroscopy IX. Direct determinations of optical purities and correlations of absolute configurations of α-amino acids. J Am Chem Soc 91(18):5150–5155CrossRefGoogle Scholar
  61. 61.
    Pirkle WH, Rinaldi PL (1977) Nuclear magnetic resonance determination of enantiomeric compositions of oxaziridines using chiral solvating agents. J Org Chem 42(20):3217–3219CrossRefGoogle Scholar
  62. 62.
    Pirkle WH, Sikkenga DL (1977) The use of chiral solvating agents for nuclear magnetic resonance determination of enantiomeric purity and absolute configuration of lactones. Consequences of three-point interactions. J Org Chem 42(8):1370–1374CrossRefGoogle Scholar
  63. 63.
    Pirkle WH, Sikkenga DL, Pavlin MS (1977) Nuclear magnetic resonance determination of enantiomeric composition and absolute configuration of γ-lactones using chiral 2,2,2-trifluoro-1-(9-anthryl)ethanol. J Org Chem 42(2):384–387CrossRefGoogle Scholar
  64. 64.
    Pirkle WH, Rinaldi PL (1978) Erratum: nuclear magnetic resonance determination of enantiomeric compositions of oxaziridines using chiral solvating agents (Journal of Organic Chemistry (1977) 42 (3217)). J Org Chem 43(26):5027CrossRefGoogle Scholar
  65. 65.
    Pirkle WH, Boeder CW (1977) Estimation of allene optical purities by nuclear magnetic resonance. J Org Chem 42(23):3697–3700CrossRefGoogle Scholar
  66. 66.
    Pirkle WH, Hoekstra MS (1974) An example of automated liquid chromatography. Synthesis of a broad-spectrum resolving agent and resolution of 1-(1-naphthyl)-2,2,2-trifluoroethanol. J Org Chem 39(26):3904–3906CrossRefGoogle Scholar
  67. 67.
    Pirkle WH, Sikkenga DL (1975) Use of achiral shift reagents to indicate relative stabilities of diastereomeric solvates. J Org Chem 40(23):3430–3434CrossRefGoogle Scholar
  68. 68.
    Pirkle WH, Hoekstra MS, Miller WH (1976) Electronic effects in asymmetric induction. Reaction of para-substituted phenylsulfinyl chlorides with S-(+)-1-(1-naphthyl)-2,2,2-trifluoroethanol. Tetrahedron Lett 17(25):2109–2112CrossRefGoogle Scholar
  69. 69.
    Pirkle WH, Sikkenga DL (1976) Resolution of optical isomers by liquid chromatography. J Chromatogr A 123(2):400–404CrossRefGoogle Scholar
  70. 70.
    Pirkle WH, House DW, Finn JM (1980) Broad spectrum resolution of optical isomers using chiral high-performance liquid chromatographic bonded phases. J Chromatogr 192(1):143–158CrossRefGoogle Scholar
  71. 71.
    Pirkle WH, House DW (1979) Chiral high-pressure liquid chromatographic stationary phases 1. Separation of the enantiomers of sulfoxides, amines, amino acids, alcohols, hydroxy acids, lactones, and mercaptans. J Org Chem 44(12):1957–1960CrossRefGoogle Scholar
  72. 72.
    Pirkle WH, Tsipouras A (1984) Direct liquid chromatographic separation of benzodiazepinone enantiomers. J Chromatogr 291:291–298CrossRefGoogle Scholar
  73. 73.
    Pirkle WH, Murray PG (1990) The separation of the enantiomers of a variety of non-steroidal anti-inflammatory drugs (NSAIDS) as their anilide derivatives using a chiral stationary phase. J Liq Chromatogr 13(11):2123–2134CrossRefGoogle Scholar
  74. 74.
    Pirkle WH, Tsipouras A, Sowin TJ (1985) Preparative separation of enantiomers by flash chromatography. J Chromatogr A 319(C): 392–395Google Scholar
  75. 75.
    Pirkle WH, Welch CJ, Hyun MH (1983) A chiral recognition model for the chromatographic resolution of N-acylated 1-aryl-1-aminoalkanes. J Org Chem 48(25):5022–5026CrossRefGoogle Scholar
  76. 76.
    Pirkle WH, Welch CJ (1984) Chromatographic separation of the enantiomers of acylated amines on chiral stationary phases. J Org Chem 49(1):138–140CrossRefGoogle Scholar
  77. 77.
    Pirkle WH et al (1984) Chromatographic separation of the enantiomers of N-acylated heterocyclic amines. J Org Chem 49(13):2504–2506CrossRefGoogle Scholar
  78. 78.
    Pirkle WH, McCune JE (1989) Separation of the enantiomers of N-protected α-amino acids as anilide and 3,5-dimethylanilide derivatives. J Chromatogr 479(2):419–423Google Scholar
  79. 79.
    Pirkle WH, Hamper BC (1988) Chromatographic separation of the enantiomers of 1,3-dithiolane-1-oxides. J Chromatogr 450(2):199–210CrossRefGoogle Scholar
  80. 80.
    Pirkle WH et al (1985) Chromatographic separation of the enantiomers of 2-carboalkoxyindolines and N-aryl-α-amino esters on chiral stationary phases derived from N-(3,5-dinitrobenzoyl)-α-amino acids. J Chromatogr A 348(C): 89–96Google Scholar
  81. 81.
    Pirkle WH, Burke JA (1992) Separation of the enantiomers of the 3,5-dinitrobenzamide derivatives of α-amino phosphonates on four chiral stationary phases. J Chromatogr 598(2):159–167CrossRefGoogle Scholar
  82. 82.
    Pirkle WH, Sowin TJ (1987) Direct liquid chromatographic separation of phthalide enantiomers. J Chromatogr A 387(C): 313–321Google Scholar
  83. 83.
    Pirkle WH, McCune JE (1988) An improved chiral stationary phase for the facile separation of enantiomers. J Chromatogr A 441(2):311–322CrossRefGoogle Scholar
  84. 84.
    Pirkle WH, McCune JE (1989) Improved chiral stationary phase for the separation of the enantiomers of chiral acids as their anilide derivatives. J Chromatogr A 471(C):271–281Google Scholar
  85. 85.
    Pirkle WH, Welch CJ, Zych AJ (1993) Chromatographic investigation of the slowly interconverting atropisomers of hindered naphthamides. J Chromatogr 648(1):101–109CrossRefGoogle Scholar
  86. 86.
    Pirkle WH et al (1984) A rational approach to the design of highly effective chiral stationary phases for the liquid chromatographic separation of enantiomers. J Pharm Biomed Anal 2(2):173–181CrossRefGoogle Scholar
  87. 87.
    Pirkle WH, Finn JM (1981) Chiral high-pressure liquid chromatographic stationary phases. 3. General resolution of arylalkylcarbinols. J Org Chem 46(14):2935–2938CrossRefGoogle Scholar
  88. 88.
    Pirkle WH et al (1981) A widely useful chiral stationary phase for the high-performance liquid chromatography separation of enantiomers. J Am Chem Soc 103(13):3964–3966CrossRefGoogle Scholar
  89. 89.
    Pirkle WH, Schreiner JL (1981) Chiral high-pressure liquid chromatographic stationary phases. 4. Separation of the enantiomers of bi-P-naphthols and analogues. J Org Chem 46(24):4988–4991CrossRefGoogle Scholar
  90. 90.
    Pirkle WH, Finn JM (1982) Preparative resolution of racemates on a chiral liquid chromatography column. J Org Chem 47(21):4037–4040CrossRefGoogle Scholar
  91. 91.
    Pirkle WH, Tsipouras A, Hyun MH (1986) Use of chiral stationary phases for the chromatographic determination of enantiomeric purity and absolute configuration of some β-lactams. J Chromatogr 358(2):377–384Google Scholar
  92. 92.
    Lee W et al (2011) Assessing chiral self-recognition using chiral stationary phases. Tetrahedron 67(37):7143–7147CrossRefGoogle Scholar
  93. 93.
    Pirkle WH, Hyun MH (1985) α-arylalkylamine-derived chiral stationary phases. Evaluation of urea linkages. J Chromatogr A 322(C): 295–307Google Scholar
  94. 94.
    Pirkle WH, Hyun MH (1985) Effect of interstrand distance upon chiral recognition by a chiral stationary phase. J Chromatogr A 328:1–9CrossRefGoogle Scholar
  95. 95.
    Pirkle WH, Hyun MH (1984) A chiral stationary phase for the facile resolution of amino acids, amino alcohols, and amines as the N-3,5-dinitrobenzoyl derivatives. J Org Chem 49(17):3043–3046CrossRefGoogle Scholar
  96. 96.
    Pirkle WH, Hyun MH (1985) Reversed-phase chromatographic resolution of N-(3,5-dinitrobezoyl)-α-amino acids on chiral stationary phases. J Chromatogr A 322(C): 287–293Google Scholar
  97. 97.
    Pirkle WH et al (1987) Separation of some enantiomeric di- and tripeptides on chiral stationary phases. J Chromatogr A 398(C): 203–209Google Scholar
  98. 98.
    Griffith OW et al (1986) Liquid chromatographic separation of enantiomers of β-amino acids using a chiral stationary phase. J Chromatogr A 362(C): 345–352Google Scholar
  99. 99.
    Pirkle WH, Welch CJ, Hyun MH (1992) Concerning the role of face-to-edge π–π interactions in chiral recognition. J Chromatogr 607(1):126–130CrossRefGoogle Scholar
  100. 100.
    Hyun MH, Ryoo JJ, Pirkle WH (2000) Experimental support differenciating two proposed chiral recognition models for the resolution of N-(3,5-Dinitrobenzoyl)-α-arylalkylamines on high-performance liquid chromatography chiral stationary phases. J Chromatogr A 886(1–2):47–53Google Scholar
  101. 101.
    Pirkle WH, Mahler G, Hyun MH (1986) Separation of the enantiomers of 3,5-dinitrophenyl carbamates and 3,5-dinitrophenyl ureas. J Liq Chromatogr 9:443–453CrossRefGoogle Scholar
  102. 102.
    Pirkle WH, Hyun MH, Bank B (1984) A rational approach to the design of highly-effective chiral stationary phases. J Chromatogr A 316:585–604CrossRefGoogle Scholar
  103. 103.
    Pirkle WH, Yamamoto S (1983) Bunseki Kagaku 32:345CrossRefGoogle Scholar
  104. 104.
    Pirkle WH, Hyun MH (1985) Preparation and use of hydantion-based chiral stationary phases. J Chromatogr A 322(C): 309–320Google Scholar
  105. 105.
    Pirkle WH, Pochapsky TC (1986) Erratum: a new, easily accessible reciprocal chiral stationary phase for the chromatographic separation of enantiomers (Journal of the American Chemical Society (1986) 108 (352–354)). J Am Chem Soc 108(9):2492CrossRefGoogle Scholar
  106. 106.
    Pirkle WH et al (1986) Useful and easily prepared chiral stationary phases for the direct chromatographic separation of the enantiomers of a variety of derivatized amines, amino acids, alcohols, and related compounds. J Org Chem 51(25):4991–5000CrossRefGoogle Scholar
  107. 107.
    Pirkle WH, Deming KC, Burke Iii JA (1991) A chiral stationary phase which affords unusually high levels of enantioselectivity. Chirality 3(3): 183–187Google Scholar
  108. 108.
    Pirkle WH, Pochapsky TC (1986) Generation of extreme selectivity in chiral recognition. J Chromatogr A 369(C): 175–177Google Scholar
  109. 109.
    Pirkle WH, Readnour RS (1991) Chromatographic approach to the measurement of the interstrand distance for some chiral bonded phases. Anal Chem 63(1):16–20CrossRefGoogle Scholar
  110. 110.
    Pirkle WH, Bowen WE, Vuong DV (1994) Liquid chromatographic separation of the enantiomers of cyclic β-amino esters as their N-3,5-dinitrobenzoyl derivatives. J Chromatogr A 676(2):297–302CrossRefGoogle Scholar
  111. 111.
    Pirkle WH, Sowin TJ (1987) Design, preparation and performance of a phthalide-based chiral stationary phase. J Chromatogr A 396(C): 83–92Google Scholar
  112. 112.
    Hyun MH, Pirkle WH (1987) Preparation and evaluation of a chiral stationary phase bearing both π-acidic and -basic sites. J Chromatogr A 393(2):357–365CrossRefGoogle Scholar
  113. 113.
    Pirkle WH, Welch CJ (1991) Chromatographic separation of underivatized naproxen enantiomers. J Liq Chromatogr 14(18):3387–3396Google Scholar
  114. 114.
    Pirkle WH et al (1992) Target-directed design of chiral stationary phases. Anal Proc 29:225–227CrossRefGoogle Scholar
  115. 115.
    Pirkle WH, Burke JA III (1991) Chiral stationary phase designed for β-blockers. J Chromatogr 557(1–2):173–185Google Scholar
  116. 116.
    Pirkle WH, Burke JA (1989) Preparation of a chiral stationary phase from an α-amino phosphonate. Chirality 1:57–62CrossRefGoogle Scholar
  117. 117.
    Pirkle WH, Lee W (2010) Separation of the enantiomers of β-blockers using brush type chiral stationary phase derived from conformationally rigid α-amino β-lactam. Bull Korean Chem Soc 31(3):620–623CrossRefGoogle Scholar
  118. 118.
    Pirkle WH, Welch CJ, Lamm B (1992) Design, synthesis, and evaluation of an improved enantioselective naproxen selector. J Org Chem 57(14):3854–3860CrossRefGoogle Scholar
  119. 119.
    Pirkle WH, Liu Y (1994) Design, synthesis, resolution, determination of absolute configuration, and evaluation of a chiral naproxen selector. J Org Chem 59(23):6911–6916CrossRefGoogle Scholar
  120. 120.
    Pirkle WH, Liu Y (1996) Incremental development of chiral selectors for underivatized profens. J Chromatogr A 736(1–2):31–38Google Scholar
  121. 121.
    Pirkle WH, Liu Y (1996) On the relevance of face-to-edge π–π interactions to chiral recognition. J Chromatogr A 749(1–2):19–24Google Scholar
  122. 122.
    Pirkle WH, Welch CJ (1994) Use of simultaneous face to face and face to edge π–π interactions to facilitate chiral recognition. Tetrahedron Asymmetr 5(5):777–780CrossRefGoogle Scholar
  123. 123.
    Pirkle WH, Welch CJ (1992) An improved chiral stationary phase for the chromatographic separation of underivatized naproxen enantiomers. J Liq Chromatogr 15(11):1947–1955CrossRefGoogle Scholar
  124. 124.
    Pirkle WH, Koscho ME, Wu Z (1996) High-performance liquid chromatographic separation of the enantiomers of N-aryloxazolinones, N-aryl thiazolinones and their sulfur derivatives on a synthetic chiral stationary phase. J Chromatogr A 726(1–2):91–97Google Scholar
  125. 125.
    Pirkle WH et al (1996) Facile separation of the enantiomers of diethyl N-(aryl)-1-amino-1-arylmethanephosphonates on a rationally designed chiral stationary phase. J Chromatogr A 721(2):241–246CrossRefGoogle Scholar
  126. 126.
    Pirkle WH et al (1996) Resolution and determination of the enantiomeric purity and absolute configurations of α-aryl-α-hydroxymethanephosphonates. Tetrahedron Asymmetr 7(8):2173–2176CrossRefGoogle Scholar
  127. 127.
    Pirkle WH, Gan KZ, Brice LJ (1996) The enhancement of enantioselectivity by halogen substituents. Tetrahedron Asymmetr 7(10):2813–2816CrossRefGoogle Scholar
  128. 128.
    Pirkle WH, Gan KZ (1997) Facile and predictable means of separating the enantiomers of 5-arylhydantoins. J Chromatogr A 790(1–2):65–71Google Scholar
  129. 129.
    Villani C, Pirkle WH (1995) Chromatographic resolution of the interconverting stereoisomers of hindered sulfinyl and sulfonyl naphthalene derivatives. Tetrahedron Asymmetr 6(1):27–30CrossRefGoogle Scholar
  130. 130.
    Pirkle WH, Koscho ME (1997) Predictable chromatographic separations of enantiomers: aryl allenic acids and their derivatives. J Chromatogr A 761(1–2):65–70Google Scholar
  131. 131.
    Pirkle WH, Spence PL (1998) Chiral recognition of phthalides and lactams. Chirality 10(5):430–433CrossRefGoogle Scholar
  132. 132.
    Pirkle WH, Spence PL (1997) Enantiodiffertiation of aryl-substituted heterocycles: a mechanistic study using γ-lactones. J Chromatogr A 775(1–2):81–90Google Scholar
  133. 133.
    Wolf C, Pirkle WH (1998) Synthesis and evaluation of a copolymeric chiral stationary phase. J Chromatogr A 799(1–2):177–184Google Scholar
  134. 134.
    Pirkle WH, Brice LJ, Terfloth GJ (1996) Liquid and subcritical CO2 separations of enantiomers on a broadly applicable polysiloxane chiral stationary phase. J Chromatogr A 753(1):109–119CrossRefGoogle Scholar
  135. 135.
    Pirkle WH, Murray PG (1993) Chiral stationary phase design. Use of intercalative effects to enhance enantioselectivity. J Chromatogr 641(1):11–19CrossRefGoogle Scholar
  136. 136.
    Pirkle WH, Murray PG (1996) Observations relevant to the differential intercalation of enantiomers between the strands of brush-type chiral stationary phases. J Chromatogr A 719(2):299–305CrossRefGoogle Scholar
  137. 137.
    Pirkle WH, Koscho ME (1999) Structural optimization of a chiral selector for use in preparative enantioselective chromatography. J Chromatogr A 840(2):151–158CrossRefGoogle Scholar
  138. 138.
    Pirkle WH, Welch CJ (1992) Effect of superfluous remote polar functionality on chiral recognition. J Chromatogr 589(1–2):45–51Google Scholar
  139. 139.
    Pirkle WH, Murray PG, Burke JA (1993) Use of homologous series of analytes as mechanistic probes to investigate the origins of enantioselectivity on two chiral stationary phases. J Chromatogr 641(1):21–29CrossRefGoogle Scholar
  140. 140.
    Pirkle WH, Bowen WE (1994) Chiral stationary phase design: a study in optimization. J High Resolut Chromatogr 17:629–633CrossRefGoogle Scholar
  141. 141.
    Pirkle WH et al (1994) Doubly tethered tertiary amide selectors. Modified version of Doyle et al.’s naproxen chiral stationary phase. J Chromatogr A 659(1):69–74CrossRefGoogle Scholar
  142. 142.
    Wolf C, Pirkle WH (2002) Conformational effects on the enantioselective recognition of 4-(3,5-dinitrobenzamido)-1,2,3,4-tetrahydrophenanthrene derivatives by a Naproxen-derived chiral stationary phase. Tetrahedron 58(18):3597–3603CrossRefGoogle Scholar
  143. 143.
    Schleimer LM, Pirkle WH, Schurig V (1994) Enantiomer separation by high-performance liquid chromatography on polysiloxane-based chiral stationary phases. J Chromatogr A 679(1):23–34CrossRefGoogle Scholar
  144. 144.
    Terfloth GJ et al (1995) Broadly applicable polysiloxane-based chiral stationary phase for high-performance liquid chromatography and supercritical fluid chromatography. J Chromatogr A 705(2):185–194CrossRefGoogle Scholar
  145. 145.
    Kosaka M et al (2003) Enantioresolution and absolute configurations of chiral meta-substituted diphenylmethanols as determined by x-ray crystallographic and 1H NMR anisotropy methods. Chirality 15(4):324–328CrossRefGoogle Scholar
  146. 146.
    Naito J et al (2004) Enantioresolution of fluorinated diphenylmethanols and determination of their absolute configurations by X-ray crystallographic and 1H NMR anisotropy methods. Chirality 16(1):22–35CrossRefGoogle Scholar
  147. 147.
    Job GE et al (2004) The effects of aromatic substituents on the chromatographic enantioseparation of diarylmethyl esters with the Whelk-O1 chiral stationary phase. J Chromatogr A 1055(1–2):41–53Google Scholar
  148. 148.
    Koscho ME, Spence PL, Pirkle WH (2005) Chiral recognition in the solid state: crystallographically characterized diastereomeric co-crystals between a synthetic chiral selector (Whelk-O1) and a representative chiral analyte. Tetrahedron Asymmetr 16(19):3147–3153CrossRefGoogle Scholar
  149. 149.
    Snyder SE, Carey JR, Pirkle WH (2005) Biphasic enantioselective partitioning studies using small-molecule chiral selectors. Tetrahedron 61(31):7562–7567CrossRefGoogle Scholar
  150. 150.
    Snyder SE et al (2007) Strong enantioselective self-recognition of a small chiral molecule. Org Lett 9(12):2341–2343CrossRefGoogle Scholar
  151. 151.
    Perrin SR et al (2007) Purification of difluoromethylornithine by global process optimization: coupling of chemistry and chromatography with enantioselective crystallization. Org Process Res Dev 11(5):817–824CrossRefGoogle Scholar
  152. 152.
    Snyder SE, Shvets AB, Pirkle WH (2002) Enantioselective nucleophilic aromatic substitution with small-molecule chiral selectors. Helv Chim Acta 85(11):3605–3615CrossRefGoogle Scholar
  153. 153.
    Snyder SE et al (2005) Formation of stable Meisenheimer adduct ion pairs in apolar solvents: implications for stereoselective reactions. J Org Chem 70(10):4073–4081CrossRefGoogle Scholar
  154. 154.
    Snyder SE, Pirkle WH (2002) Enantioselective hydrolysis of N-acylated α-amino esters at a biphasic interface: Tandem reaction kinetic resolution using a chiral complexing agent. Org Lett 4(19):3283–3286CrossRefGoogle Scholar
  155. 155.
    Pirkle WH, Snyder SE (2001) Two-component chiral phase transfer catalysts: enantioselective esterification of an N-acylated amino acid. Org Lett 3(12):1821–1823CrossRefGoogle Scholar
  156. 156.
    Koscho ME, Pirkle WH (2005) Investigation of a broadly applicable chiral selector used in enantioselective chromatography (Whelk-O 1) as a chiral solvating agent for NMR determination of enantiomeric composition. Tetrahedron Asymmetr 16(20):3345–3351CrossRefGoogle Scholar
  157. 157.
    Hyun MH, Pirkle WH (2000) Liquid chromatographic separation of the stereoisomers of thiazide diuretics. J Chromatogr A 876(1–2):221–227Google Scholar
  158. 158.
    Kacprzak KM, Lindner W (2011) Novel Pirkle-type quinine 3,5-dinitrophenylcarbamate chiral stationary phase implementing click chemistry. J Sep Sci 34(18):2391–2396CrossRefGoogle Scholar
  159. 159.
    Wu H et al (2012) Investigation of brush-type chiral stationary phases based on O, O′-diaroyl tartardiamide and O, O′-bis-(arylcarbamoyl) tartardiamide. J Sep Sci 35(3):351–358CrossRefGoogle Scholar
  160. 160.
    Wei WJ et al (2010) Preparation and enantioseparation of a mixed selector chiral stationary phase derived from benzoylated tartaric acid and 1,2-diphenylethylenediamine. Chirality 22(6):604–611Google Scholar
  161. 161.
    Cancelliere G et al (2010) Transition from enantioselective high performance to ultra-high performance liquid chromatography: a case study of a brush-type chiral stationary phase based on sub-5-micron to sub-2-micron silica particles. J Chromatogr A 1217(7):990–999CrossRefGoogle Scholar
  162. 162.
    Gasparrini F, Misiti D, Villani C (2001) High-performance liquid chromatography chiral stationary phases based on low-molecular-mass selectors. J Chromatogr A 906(1–2):35–50Google Scholar
  163. 163.
    Yilmaz H et al (2010) Resolution of (±)-β-methylphenylethylamine by a novel chiral stationary phase for Pirkle-type column chromatography. Chirality 22(2):252–257Google Scholar
  164. 164.
    Moiteiro C et al (2006) Development of novel brush-type chiral stationary phases based on terpenoid selectors: HPLC evaluation and theoretical investigation of enantioselective binding interactions. Tetrahedron Asymmetr 17(23):3248–3264CrossRefGoogle Scholar
  165. 165.
    Tan X et al (2007) Preparation of a new chiral stationary phase for HPLC based on the (R)-1-phenyl-2-(-4-methylphenyl)ethylamine amide derivative of (S)-valine and 2-chloro-3,5-dinitrobenzoic acid: enantioseparation of amino acid derivatives and pyrethroid insecticides. J Sep Sci 30(12):1888–1892CrossRefGoogle Scholar
  166. 166.
    Forjan DM, Kontrec D, Vinković V (2006) Performance of brush-type HPLC chiral stationary phases with tertiary amide in the connecting tether. Chirality 18(10):857–869CrossRefGoogle Scholar
  167. 167.
    Pinto M et al (2011) Fases Estacionárias Quirais baseadas em Derivados Xantónicos, in Boletim da Propriedade Industrial no 2011/01/21. PortugalGoogle Scholar
  168. 168.
    Pinto MMM, Sousa ME, Nascimento MSJ (2005) Xanthone derivatives: new insights in biological activities. Curr Med Chem 12(21):2517–2538CrossRefGoogle Scholar
  169. 169.
    Pinto MMM, Castanheiro RAP (2009) Natural prenylated xanthones: chemistry and biological activities. In: Brahmachari G (ed) Natural products, chemistry, biochemistry and pharmacology. Narosa Publishing House, West Bengal, pp 520–675Google Scholar
  170. 170.
    Pinto E et al (2011) Antifungal activity of xanthones: evaluation of their effect on ergosterol biosynthesis by high-performance liquid chromatography. Chem Biol Drug Des 77(3):212–222CrossRefGoogle Scholar
  171. 171.
    Paiva AM et al (2012) Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line. Med Chem Res 21(5):552–558Google Scholar
  172. 172.
    Castanheiro RAP et al (2007) Dihydroxyxanthones prenylated derivatives: synthesis, structure elucidation, and growth inhibitory activity on human tumor cell lines with improvement of selectivity for MCF-7. Bioorg Med Chem 15(18):6080–6088CrossRefGoogle Scholar
  173. 173.
    Correia-Da-Silva M et al (2011) Polysulfated xanthones: multipathway development of a new generation of dual anticoagulant/antiplatelet agents. J Med Chem 54(15):5373–5384CrossRefGoogle Scholar
  174. 174.
    Costa E et al (2010) Synthesis of xanthones and benzophenones as inhibitors of tumor cell growth. Lett Drug Des Discovery 7(7):487–493CrossRefGoogle Scholar
  175. 175.
    Palmeira A et al (2010) Insights into the in vitro antitumor mechanism of action of a new pyranoxanthone. Chem Biol Drug Des 76(1):43–58CrossRefGoogle Scholar
  176. 176.
    Palmeira A et al (2012) Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones. Biochem Pharmacol 83(1):57–68CrossRefGoogle Scholar
  177. 177.
    Marona H et al (2008) Anticonvulsant activity of some xanthone derivatives. Bioorg Med Chem 16(15):7234–7244CrossRefGoogle Scholar
  178. 178.
    Marona H (1998) Synthesis and anticonvulsant effects of some aminoalkanolic derivatives of xanthone. Pharmazie 53(10):672–676Google Scholar
  179. 179.
    Pinto MMM, Sousa EP (2003) Natural and synthetic xanthonolognoids: chemistry and biological activities. Curr Med Chem 10(1):1–12CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Carla Fernandes
    • 1
    • 2
  • Maria Elizabeth Tiritan
    • 1
    • 2
    • 3
  • Madalena Pinto
    • 1
    • 2
    Email author
  1. 1.Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP)PortoPortugal
  2. 2.Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de FarmáciaUniversidade do PortoPortoPortugal
  3. 3.Centro de Investigação em Ciências da Saúde, Instituto Superior de Ciências da Saúde-Norte-CESPU (CICS-ISCS-N-CESPU)Gandra PRDPortugal

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