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
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1194
Mislow K (1999) Molecular chirality. Top Stereochem 22:1–82
Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1197
Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1198
Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, pp 298–302
Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, p 300
Mislow K, Siegel J (1984) Stereoisomerism and local chirality. J Am Chem Soc 106:3319–3328
Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, p 301
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
Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York
Anslyn EV, Dougherty DA (2006) Modern physical organic chemistry. University Science Books, Sausalito, pp 297–351
Carroll FA (1998) Perspectives on structure and mechanism in organic chemistry. Brooks/Cole Publishing Company, Pacific Grove, pp 58–118
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
Davankov VA (1991) Should the terminology used in chirality be more precise? Chirality 3:442
Helmchen G (1997) Glossary of problematic terms in organic stereochemistry. Enantiomer 2:315–318
Bentley R (2010) Chiral: a confusing etymology. Chirality 22:1–2
Gal J (2011) Louis Pasteur, language, and molecular chirality–I. Background and dissymmetry. Chirality 23:1–16
Eliel EL (1997) Infelicitous stereochemical nomenclature. Chirality 9:428–430
Gal J (1998) Problems of stereochemical nomenclature and terminology. 1. The homochiral controversy. Its nature, origins, and a proposed solution. Enantiomer 3:263–273
Gal J (2007) Carl Friedrich Naumann and the introduction of enantio terminology: a review and analysis on the 150th anniversary. Chirality 19:89–98
Pifferi G, Perucca E (1995) The cost benefit ratio of enantiomeric drugs. Eur J Drug Metab Pharmacokinet 20:15–25
Han H, Yoon J, Janda KD (1998) An efficient asymmetric route to 2,3-diaminobutanoic acids. J Org Chem 63:2045–2048
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
Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York, p 1192
Krebs HA (1970) The history of the tricarboxylic acid cycle. Perspect Biol Med 14:154–170
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
Mauskopf SH (1976) Crystals and compounds: molecular structure and composition in nineteenth-century French science. Trans Am Phil Soc 66:5–80
Chautard J (1853) Mémoire sur l’acide camphorique gauche et sur le camphre gauche. Compt Rend Acad Sci 37:166–7
Van ‘t Hoff JH (1874) Sur le formules de structure dans l'espace. Arch Neerl 9:1–10
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
Ramberg PJ (2003) Chemical structure, spatial arrangement: the early history of stereochemistry 1874–1914. Ashgate Publishing Limited, Aldershot, pp 53–109
Ramsay OB (1981) Stereochemistry. Heyden, London, pp 81–97
Pasteur L (1857) Mémoire sur la fermentation alcoolique. C R Séances Acad Sci 45:1032–1036
Pasteur L (1858) Mémoire sur la fermentation de l'acide tartrique. C R Séances Acad Sci 46:615–618
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
Lichtenthaler FW (1992) Emil Fischer’s proof of the configuration of sugars. A centennial tribute. Angew Chem Int Ed 31:1541–1546
Fischer E (1894) Einfluss der Konfiguration auf der Wirkung der Enzyme. Ber Dtsch Chem Ges 27:2985–2993
Fischer E (1891) Ueber die Configuration des Traubezuckers und seiner Isomeren Ber dtsch chem. Ges 24:1836–1845
Ramberg PJ (2003) Chemical structure, spatial arrangement: the early history of stereochemistry 1874–1914. Ashgate Publishing Limited, Aldershot, pp 243–276
Piutti A (1886) Ein neues Asparagin. Ber Dtsch Chem Ges 19:1691–1695
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
Prüll C-R, Maehle A-H, Halliwell RF (2009) A short history of the drug receptor concept. Palgrave MacMillan, Basingstoke, p 1
Ehrlich P, Morgenroth J (1900) Ueber Haemolysine. Dritte Mittheilung. Berliner klin Wochenschrift 37:453–458
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
Vauquelin LN, Robiquet PJ (1806) La découverte d'un nouveau principe végétal dans le suc des asperges. Ann Chim 57:88–93
Piutti A (1888) Sintesi e costituzione delle asparagine. Gazz Chim Ital 18:457–472
Cushny AR (1920) On optical isomers. V Tropeines J Pharmacol 15:105–127
Cushny AR (1909) Further note on adrenalin isomers. J Physiol 38:259–262
Cushny AR (1926) Biological relations of optically isomeric substances. The Williams and Wilkins Company, Baltimore
Crossley R (1992) The relevance of chirality to the study of biological activity. Tetrahedron 48:8155–8178
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
Eichelbaum M, Testa B, Somogyi A (eds) (2003) Stereochemical aspects of drug action and disposition. Springer, Berlin
Ariëns EJ, Soudijn W, Timmermans PBMWM (eds) (1983) Stereochemistry and biological activity of drugs. Blackwell Scientific Publications, Oxford
Ariëns EJ (1984) Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur J Clin Pharmacol 26:663–668
Ariëns EJ, Wuis EW (1987) Bias in pharmacokinetics and clinical pharmacology. Clin Pharmacol Ther 42:361–363
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
Anonymous (1992) Fed Reg 5(102):22249
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
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
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
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
Corresponding author
Editor information
Editors and Affiliations
Rights 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
DOI: https://doi.org/10.1007/128_2013_435
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-03238-2
Online ISBN: 978-3-319-03239-9
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)