Skip to main content

Molecular Chirality: Language, History, and Significance

  • Chapter
  • First Online:

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 340))

Abstract

In this chapter some background material concerning molecular chirality and enantiomerism is presented. First some basic chemical-molecular aspects of chirality are reviewed, after which certain relevant terminology whose use in the literature has been problematic is discussed. Then an overview is provided of some of the early discoveries that laid the foundations of the science of molecular chirality in chemistry and biology, including the discovery of the phenomenon of molecular chirality by L. Pasteur, the proposals for the asymmetric carbon atom by J.H. van ‘t Hoff and J.A. Lebel, Pasteur’s discovery of biological enantioselectivity, the discovery of enantioselectivity at biological receptors by A. Piutti, the studies of enzymatic stereoselectivity by E. Fischer, and the work on enantioselectivity in pharmacology by A. Cushny. Finally, the role of molecular chirality in pharmacotherapy and new-drug development, arguably one of the main driving forces for the current intense interest in the phenomenon of molecular chirality, is discussed.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1194

    Google Scholar 

  2. Mislow K (1999) Molecular chirality. Top Stereochem 22:1–82

    CAS  Google Scholar 

  3. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1197

    Google Scholar 

  4. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1198

    Google Scholar 

  5. Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, pp 298–302

    Google Scholar 

  6. Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, p 300

    Google Scholar 

  7. Mislow K, Siegel J (1984) Stereoisomerism and local chirality. J Am Chem Soc 106:3319–3328

    Article  CAS  Google Scholar 

  8. Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, p 301

    Google Scholar 

  9. Gal J (2011) Stereochemical vocabulary for structures that are chiral but not asymmetric: history, analysis, and proposal for a rational terminology. Chirality 23:647–659

    Article  CAS  Google Scholar 

  10. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York

    Google Scholar 

  11. Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, pp 297–351

    Google Scholar 

  12. Carroll FA (1998) Perspectives on structure and mechanism in organic chemistry. Brooks/Cole Publishing Company, Pacific Grove, pp 58–118

    Google Scholar 

  13. Nicolaou KC, Boddy CNC, Siegel JS (2001) Does CIP nomenclature adequately handle multiple stereoelements? A case study of vancomycin and cognates. Angew Chem Int Ed 40:701–704

    Article  CAS  Google Scholar 

  14. Davankov VA (1991) Should the terminology used in chirality be more precise? Chirality 3:442

    Article  Google Scholar 

  15. Helmchen G (1997) Glossary of problematic terms in organic stereochemistry. Enantiomer 2:315–318

    CAS  Google Scholar 

  16. Bentley R (2010) Chiral: a confusing etymology. Chirality 22:1–2

    Article  CAS  Google Scholar 

  17. Gal J (2011) Louis Pasteur, language, and molecular chirality–I. Background and dissymmetry. Chirality 23:1–16

    Article  CAS  Google Scholar 

  18. Eliel EL (1997) Infelicitous stereochemical nomenclature. Chirality 9:428–430

    Article  CAS  Google Scholar 

  19. Gal J (1998) Problems of stereochemical nomenclature and terminology. 1. The homochiral controversy. Its nature, origins, and a proposed solution. Enantiomer 3:263–273

    CAS  Google Scholar 

  20. Gal J (2007) Carl Friedrich Naumann and the introduction of enantio terminology: a review and analysis on the 150th anniversary. Chirality 19:89–98

    Article  CAS  Google Scholar 

  21. Pifferi G, Perucca E (1995) The cost benefit ratio of enantiomeric drugs. Eur J Drug Metab Pharmacokinet 20:15–25

    Article  CAS  Google Scholar 

  22. Han H, Yoon J, Janda KD (1998) An efficient asymmetric route to 2,3-diaminobutanoic acids. J Org Chem 63:2045–2048

    Article  CAS  Google Scholar 

  23. Kagan H, Gopalaiah K (2011) Early history of asymmetric synthesis: who are the scientists who set up the basic principles and the first experiments? New J Chem 35:1933–1937

    Article  CAS  Google Scholar 

  24. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1192

    Google Scholar 

  25. Krebs HA (1970) The history of the tricarboxylic acid cycle. Perspect Biol Med 14:154–170

    CAS  Google Scholar 

  26. Pasteur L (1922) Recherches sur la dissymétrie moléculaire des produits organiques naturels. In: Pasteur Vallery-Radot L (ed) Œuvres de Pasteur, vol 1. Masson et Cie, Paris, pp 314–344

    Google Scholar 

  27. Mauskopf SH (1976) Crystals and compounds: molecular structure and composition in nineteenth-century French science. Trans Am Phil Soc 66:5–80

    Google Scholar 

  28. Chautard J (1853) Mémoire sur l’acide camphorique gauche et sur le camphre gauche. Compt Rend Acad Sci 37:166–7

    Google Scholar 

  29. Van ‘t Hoff JH (1874) Sur le formules de structure dans l'espace. Arch Neerl 9:1–10

    Google Scholar 

  30. Lebel JA (1874) Sur les relations qui existent entre les formules atomiques des corps organiques et le pouvoir rotatoire de leurs dissolutions. Bul Soc Chim Paris 22:337–347

    Google Scholar 

  31. Ramberg PJ (2003) Chemical structure, spatial arrangement: the early history of stereochemistry 1874–1914. Ashgate Publishing Limited, Aldershot, pp 53–109

    Google Scholar 

  32. Ramsay OB (1981) Stereochemistry. Heyden, London, pp 81–97

    Google Scholar 

  33. Pasteur L (1857) Mémoire sur la fermentation alcoolique. C R Séances Acad Sci 45:1032–1036

    Google Scholar 

  34. Pasteur L (1858) Mémoire sur la fermentation de l'acide tartrique. C R Séances Acad Sci 46:615–618

    Google Scholar 

  35. Gal J (2008) The discovery of biological enantioselectivity: Louis Pasteur and the fermentation of tartaric acid – a review and analysis 150 years later. Chirality 20:5–19

    Article  CAS  Google Scholar 

  36. Lichtenthaler FW (1992) Emil Fischer’s proof of the configuration of sugars. A centennial tribute. Angew Chem Int Ed 31:1541–1546

    Article  Google Scholar 

  37. Fischer E (1894) Einfluss der Konfiguration auf der Wirkung der Enzyme. Ber Dtsch Chem Ges 27:2985–2993

    Article  CAS  Google Scholar 

  38. Fischer E (1891) Ueber die Configuration des Traubezuckers und seiner Isomeren Ber dtsch chem. Ges 24:1836–1845

    Article  Google Scholar 

  39. Ramberg PJ (2003) Chemical structure, spatial arrangement: the early history of stereochemistry 1874–1914. Ashgate Publishing Limited, Aldershot, pp 243–276

    Google Scholar 

  40. Piutti A (1886) Ein neues Asparagin. Ber Dtsch Chem Ges 19:1691–1695

    Article  Google Scholar 

  41. Gal J (2012) The discovery of stereoselectivity at biological receptors: Arnaldo Piutti and the taste of the asparagine enantiomers – history and analysis on the 125th anniversary. Chirality 24:959–976

    Article  CAS  Google Scholar 

  42. Prüll C-R, Maehle A-H, Halliwell RF (2009) A short history of the drug receptor concept. Palgrave MacMillan, Basingstoke, p 1

    Book  Google Scholar 

  43. Ehrlich P, Morgenroth J (1900) Ueber Haemolysine. Dritte Mittheilung. Berliner klin Wochenschrift 37:453–458

    Google Scholar 

  44. Langley JN (1905) On the reaction of cells and nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curare. J Physiol 33:374–413

    Google Scholar 

  45. Vauquelin LN, Robiquet PJ (1806) La découverte d'un nouveau principe végétal dans le suc des asperges. Ann Chim 57:88–93

    Google Scholar 

  46. Piutti A (1888) Sintesi e costituzione delle asparagine. Gazz Chim Ital 18:457–472

    Google Scholar 

  47. Cushny AR (1920) On optical isomers. V Tropeines J Pharmacol 15:105–127

    CAS  Google Scholar 

  48. Cushny AR (1909) Further note on adrenalin isomers. J Physiol 38:259–262

    CAS  Google Scholar 

  49. Cushny AR (1926) Biological relations of optically isomeric substances. The Williams and Wilkins Company, Baltimore

    Google Scholar 

  50. Crossley R (1992) The relevance of chirality to the study of biological activity. Tetrahedron 48:8155–8178

    Article  CAS  Google Scholar 

  51. Patel BK, Hutt AJ (2004) Stereoselectivity in drug action and disposition: an overview. In: Reddy IK, Mehvar R (eds) Chirality in drug design and development. Marcel Dekker, New York

    Google Scholar 

  52. Eichelbaum M, Testa B, Somogyi A (eds) (2003) Stereochemical aspects of drug action and disposition. Springer, Berlin

    Google Scholar 

  53. Ariëns EJ, Soudijn W, Timmermans PBMWM (eds) (1983) Stereochemistry and biological activity of drugs. Blackwell Scientific Publications, Oxford

    Google Scholar 

  54. Ariëns EJ (1984) Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur J Clin Pharmacol 26:663–668

    Article  Google Scholar 

  55. Ariëns EJ, Wuis EW (1987) Bias in pharmacokinetics and clinical pharmacology. Clin Pharmacol Ther 42:361–363

    Article  Google Scholar 

  56. Shah RR, Midgley JM, Branch SK (1998) Stereochemical origin of some clinically significant drug safety concerns: lessons for future drug development. Adverse Drug React Toxicol Rev 17:145–190

    CAS  Google Scholar 

  57. Anonymous (1992) Fed Reg 5(102):22249

    Google Scholar 

  58. Reist M, Testa B, Carrupt PA, Jung M, Schurig V (1995) Racemization, enantiomerization, diastereomerization, and epimerization – their meaning and pharmacological significance. Chirality 7:396–400

    Article  CAS  Google Scholar 

  59. Caldwell J, Hutt AJ, Fournel-Gigleux S (1988) The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem Pharmacol 37:105–114

    Article  CAS  Google Scholar 

  60. Vogel P (2003) Recent advances in asymmetric organic synthesis: principles and examples. In: Eichelbaum M, Testa B, Somogyi A (eds) Stereochemical aspects of drug action and disposition. Springer, Berlin, pp 3–44

    Chapter  Google Scholar 

Download references

Acknowledgments

Helpful information from the following individuals (listed in alphabetical order) is gratefully acknowledged: Prof. Pedro Cintas (University of Extremadura, Spain); Prof. Mark M. Green (New York University, USA); Prof. Andrew J. Hutt (University of Hertfordshire, UK). The author is deeply indebted to the Piutti family, Dr. Claudia Piutti (Nerviano Medical Sciences, Nerviano, Italy), great-granddaughter of Arnaldo Piutti; Pietro Piutti (of Conegliano, Italy), grandson of Arnaldo Piutti; and Pietro’s spouse Caterina (née Rovetto) for providing Arnaldo’s photograph and permission to reproduce it. The author is grateful to John Wiley & Sons, Inc., for permission to use text from some of his previously published articles [9, 17, 20, 35, 41].

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph Gal .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Gal, J. (2013). Molecular Chirality: Language, History, and Significance. In: Schurig, V. (eds) Differentiation of Enantiomers I. Topics in Current Chemistry, vol 340. Springer, Cham. https://doi.org/10.1007/128_2013_435

Download citation

Publish with us

Policies and ethics