Biosynthesis, total synthesis, and biological profiles of Ergot alkaloids.
The Alkaloids: Chemistry and Biology 2021 DOI: 10.1016/bs.alkal.2020.08.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | LSD |
| Keywords | Aurantioclavine Chanoclavine Chemical methodologies Clavicipitic acid Cycloclavine Ergoline Indole Isolysergol Natural products Pharmaceutical chemistry Rugulovasine Structure-activity relationship Total synthesis Ergot alkaloids: ergot Alkaloid synthesis: biosynthesis |
| Citations | 32 |
| Key findings | Ergot alkaloid research over the past 20 years has elucidated biosynthetic pathways, enabled efficient total syntheses, and identified therapeutic potential for psychiatric disorders, but side effects of ergotism remain a challenge. |
Abstract
While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.
Comparable studies
Other narrative reviews on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Study of a New Schizophrenomimetic Drug—Sernyl | 1959 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| The Pharmacology of Lysergic Acid Diethylamide: A Review | 2008 | Review | |
| Serotonin research: contributions to understanding psychoses | 2008 | Review | |
| ADVERSE REACTIONS TO PSYCHEDELIC DRUGS. A REVIEW OF THE LITERATURE | 1984 | Review |
Citations in the library
Cited by 6
- Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants Chemical Reviews November 30, 2023
- The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology International Journal of Molecular Sciences January 10, 2023
- Biological studies of clavine alkaloids targeting CNS receptors Frontiers in Psychiatry November 21, 2023
- Synthetic Strategies toward Lysergic Acid Diethylamide: Ergoline Synthesis via α-Arylation, Borrowing Hydrogen Alkylation, and C-H Insertion. The Journal of Organic Chemistry October 6, 2023
- LSD: Mechanisms and relevance to the treatment of depression Neuroscience & Biobehavioral Reviews October 10, 2025
and 1 more in the library
Cites 12
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Crystal structure of an LSD-bound human serotonin receptor Cell January 26, 2017
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
- Modern Clinical Research on LSD Neuropsychopharmacology April 27, 2017
- Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting Psychopharmacology October 24, 2018
and 7 more in the library