Eserethole Explained

Eserethole is a nitrogen-containing organic compound (C15H22N2O). It possesses a unique bicyclic structure, combining an indole and a pyrrole ring system. It is used in the synthesis of various alkaloids.[1]

Discovery

Discovery of eserethole is associated with a scientific competition in the 1930s. Two research groups were independently trying to synthesize the drug physostigmine. One group, led by Percy Julian at Howard University aimed to create d,l-eserethole as a crucial intermediate step. Another group, working under Sir Robert Robinson also reported the synthesis of d,l-eserethole around the same time.

However, the d,l-eserethole reported by Julian's group exhibited entirely different properties compared to that of Robinson's group. Ultimately, eserethole synthesized by Julian's group was proved to be the actual compound based on melting point equivalence with eserethole obtained from natural sources.[2] [3] [4] [5]

Properties

Eserethole is not an end product itself, but rather a molecule formed during the synthesis of other compounds, particularly alkaloids found in Calabar bean.

It exists as a red to dark red semi-solid and is usually stored at 253K under inert conditions. It is sparingly soluble in non-polar solvents like chloroform and slightly soluble in polar solvents like ethanol.

Eserethole contains a pyrrolo-indole aromatic ring system with a pyrrole ring attached to a indole ring. It has two stereocenters.

Uses

Eserethole is a vital building block in the synthesis of physostigmine, a naturally occurring alkaloid and acetylcholinesterase inhibitor used to treat glaucoma and delayed gastric emptying.[6] [7]

It is also intermediate in the synthesis of other alkaloids with acetylcholinesterase-inhibiting properties like (-)-physovenine, (-)-geneserine, etc.[8]

Notes and References

  1. Web site: Eserethole . BenchChem . 2024-05-15.
  2. Ault . Addison . 2008 . Percy Julian, Robert Robinson, and the Identity of Eserethole . Journal of Chemical Education . en . 85 . 11 . 1524 . 10.1021/ed085p1524 . 2008JChEd..85.1524A . 0021-9584.
  3. Web site: Percy Lavon Julian . 2024-05-15 . American Chemical Society . en.
  4. Web site: Koester . Vera . Percy Lavon Julian: Against All Odds . ChemistryViews . 2022-11-01 . 2024-05-15.
  5. Web site: The Right Chemistry, 1935 . 2024-05-15 . The Scientist Magazine® . en.
  6. Moore . Philip W. . Rasimas . J. J. . Donovan . J. W. . Physostigmine is the Antidote for Anticholinergic Syndrome . Journal of Medical Toxicology . 11 . 1 . 2015 . 1556-9039 . 25339374 . 4371033 . 10.1007/s13181-014-0442-z . 159–160.
  7. Smith . Richard . Livinghouse . Tom . 1985-01-01 . Alkaloid synthesis via the intramolecular imidate methylide 1,3-dipolar cycloaddition reaction . Tetrahedron . 41 . 17 . 3559–3568 . 10.1016/S0040-4020(01)96709-2 . 0040-4020.
  8. Node . Manabu . Hao . Xiao-jiang . Nishide . Kiyoharu . Fuji . Kaoru . 1996 . A Formal Asymmetric Synthesis of Calabar Bean Alkaloids. . Chemical and Pharmaceutical Bulletin . en . 44 . 4 . 715–719 . 10.1248/cpb.44.715 . 0009-2363.