Investigations into Calabar beans (the dried ripe seeds of Physostigma venenosum) and their alkaloidal components compose a classical scientific journey throughout some one-and-a-half centuries and not only represent a fascinating aspect of the history of medicine but which is, moreover, still ongoing at the forefront of chemical and medical discovery. Those in particular involving its major such component, l-physostigmine, have led to an understanding of some of the fundamental mechanisms occurring in physiology, pharmacology and biochemistry and, either actually or potentially (by providing a template and thereby acting as a “lead compound”) have provided a useful treatment for a variety of neurological disorders associated with irregularities in cholinergic transmission in which augmentation of cholinergic activity has proved to be beneficial.
Author(s): Brian Robinson
Publisher: Springer
Year: 2023
Language: English
Pages: 283
City: Dodrecht
Quotations
Dr Brian Robinson (May 1936-February 2023)
Preface and Acknowledgements
Chronology
Contents
Abbreviations
Chapter 1: Introduction
Chapter 2: l-Physostigmine (Eserine)
2.1 Natural Occurrence
2.2 Structure Elucidation
2.3 Syntheses of:-
2.3.1 By Early Approaches, Including the First to be Successful
2.3.2 l-Physostigmine and the 3a-alkyl-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]Indole Ring System
2.3.3 d-Physostigmine
2.4 Absolute Configuration, Together with that of the Other Structurally-Established Alkaloids of the Calabar Bean
2.5 Biogenesis
2.6 Ultraviolet Absorption Spectrum and Reaction in an Acidic Medium
2.7 Mass Spectrum
2.8 Detection, Assay and Instability
2.8.1 Qualitative and Quantitative Analysis
2.8.2 Rubreserine
2.8.3 Eserine Blue
2.8.4 Eserine Brown
Chapter 3: l-Physovenine
3.1 Isolation and Structure Elucidation
3.2 Synthesis of the
3.2.1 Racemate
3.2.2 l- and d-Enantiomers
3.2.3 3a-alkyl-3,3a,8,8a-tetrahydro-2H-furo[2,3-b]indole Ring System
3.3 Biogenesis
Chapter 4: l-Eseramine
4.1 Isolation and Structure Elucidation
4.2 Synthesis of the Racemate and the l-enantiomer
4.2.1 Racemate
4.2.2 l-enantiomer
Chapter 5: l-N(8)-Norphysostigmine
5.1 Isolation and Structure Elucidation
5.2 Synthesis of the l-enantiomer
Chapter 6: l-Geneserine
6.1 Isolation and Structure Elucidation
6.2 Synthesis of the l-enantiomer and the Racemate
Chapter 7: 1H-, 13C- and 15N-Nuclear Magnetic Resonance Spectra of the Alkaloids of the Calabar Bean
Chapter 8: Other Alkaloids That Have Been Isolated, or Allegedly So, from the Calabar Bean
8.1 Calabarine
8.2 Eseridine
8.3 Isophysostigmine
8.4 Calabatine and Calabacine
8.5 Investigations Still to Be Effected
Chapter 9: Non-Alkaloidal Components of the Calabar Bean
Chapter 10: Biological Activities of the Alkaloids of the Calabar Bean
10.1 AntiAchE Activity
10.1.1 AchE - Its Function in Neurohumoral Transmission, Structure and Inhibition
10.2 Pharmacology of l-physostigmine
10.3 Role of l-physostigmine in the Discovery of the Mechanism of Neurohumoral Transmission
10.4 AntiAchE Activities of the Minor Alkaloids of the Calabar Bean - The l-physostigmine Pharmacophore
10.5 Clinical use of l-physostigmine in Ophthalmology - Miotic Activity and the Reduction of Intraocular Pressure in Glaucoma
10.6 Use of l-physostigmine in the Treatment of: -
10.6.1 Myasthenia Gravis
10.6.2 Paraplegic Anejaculation
10.7 Use of l-physostigmine in the:-
10.7.1 Prophylactic Protection Against Intoxication by Organophosphates (Including ``Nerve Gases´´)
10.7.2 Enhancement of Cognition and Memory (Including Antiamnesic Activity in Dementia of the Alzheimer´s Type - Alzheimer´s D...
10.8 Bactericidal and Insecticidal Activities of l-Physostigmine
10.9 Prophylactic Protection with d-physostigmine Against Intoxication by Organophosphates (Including ``Nerve Gases´´)
10.10 Other Clinical Uses of l-physostigmine
10.11 Antinociceptive Activity of l-eseroline and Its Synthetic Analogues
10.12 Cytotoxicities of Rubreserine and another Structurally-Related Degradation Product of l-Physostigmine
10.13 Poisonings (Either Accidental or Malicious) with the Calabar Bean
References
Index
