Related Experiment Video
Updated: May 30, 2026
11:44
Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
Total synthesis of (-)-histrionicotoxin.
Yohei Adachi1, Noriyuki Kamei, Satoshi Yokoshima
1Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Organic Letters
|July 29, 2011
Summary
A total synthesis of (-)-histrionicotoxin was achieved using novel methods. Key steps included chirality transfer, ring formation via metathesis, and selective functionalization for an optically active bicyclo[5.4.0] system.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- (-)-Histrionicotoxin is a complex natural product with significant biological activity.
- Previous synthetic routes to histrionicotoxin and its analogs have faced challenges in stereocontrol and efficiency.
Purpose of the Study:
- To develop a novel and efficient total synthesis of (-)-histrionicotoxin.
- To establish a stereoselective route to the core bicyclo[5.4.0] framework.
- To showcase the utility of specific synthetic methodologies in complex molecule construction.
Main Methods:
- Chirality transfer from an allenylsilane to prepare a pseudosymmetrical dienyne.
- Diyne metathesis for the construction of the bicyclo[5.4.0] system in an optically active form.
- Selective diene functionalization using 5-exo-trig iodoetherification.
- Asymmetric propargylation for introducing key structural elements.
Main Results:
- Successful total synthesis of (-)-histrionicotoxin.
- Efficient construction of the optically active bicyclo[5.4.0] core.
- Demonstration of a robust synthetic strategy involving chirality transfer and metathesis.
Conclusions:
- The developed synthetic strategy provides a viable route to (-)-histrionicotoxin.
- The methodology employed is applicable to the synthesis of related natural products and analogs.
- This work advances the field of complex natural product synthesis through innovative chemical transformations.
Related Concept Videos
01:22Botulism
Botulism is a life-threatening neuroparalytic condition caused by botulinum neurotoxin, which is produced by the bacterium Clostridium botulinum, a Gram-positive, spore-forming, obligate anaerobe.In adults, the toxin enters the body in different ways: in foodborne botulism, the preformed toxin is absorbed in the intestine. In wound botulism, spores grow in injured tissue and release the toxin into the blood. Infant botulism differs mechanistically from adult forms. In infants, botulism commonly...
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
01:29Tetanus
Tetanus is a life-threatening neurological disorder characterized by persistent muscle contractions and spastic paralysis. It is caused by Clostridium tetani, a motile, Gram-positive, rod-shaped, obligate anaerobe. These bacteria produce terminal endospores, giving them a distinctive “lollipop” or “tennis-racket” appearance. They thrive in anaerobic environments, such as those found in deep puncture wounds.Once introduced into the body, the spores germinate into vegetative cells. These cells...
01:28Diphtheria
Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
01:36Types of Toxins
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
01:30Toxidromes: Clinical Features
Toxidromes are specific patterns of symptoms resulting from toxic substance exposure. They help in the identification and treatment of poisoning. The symptoms of each toxidrome group indicate poisoning by a certain class of chemicals or drugs.1. Sympathomimetic: Stimulates the sympathetic nervous system. Symptoms include agitation, increased heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature, and pupil size. Drugs like cocaine and amphetamines, along with tremors and...