Total Synthesis and Structure Revision of Halioxepine
Caroline Poock1, Markus Kalesse1,2,3
1Institute for Organic Chemistry, Gottfried Wilhelm Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|November 20, 2020
Summary
The first total synthesis of halioxepine was achieved using key 1,4-addition and halo etherification reactions. Structural confirmation involved enantiomeric building blocks and configuration analysis, establishing the molecule's precise architecture.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Halioxepine is a complex natural product with a unique molecular structure.
- Previous efforts have not achieved the total synthesis of halioxepine.
Purpose of the Study:
- To achieve the first total synthesis of halioxepine.
- To establish reliable synthetic routes for complex molecules.
Main Methods:
- Utilized a 1,4-addition reaction to construct the quaternary center at C10.
- Employed a halo etherification strategy to form the tertiary ether at C7.
- Assembled different enantiomeric building blocks to confirm structure.
Main Results:
- Successfully synthesized halioxepine.
- Determined the correct structure of halioxepine by varying enantiomeric components.
- Established the relative configuration between C10 and C15.
Conclusions:
- The first total synthesis of halioxepine has been accomplished.
- The synthetic strategy provides a robust method for constructing complex molecular architectures.
- The structural elucidation confirms the molecule's precise stereochemistry.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Related Concept Videos
01:16Adrenergic Agonists: Chemistry and Structure-Activity Relationship
3.6K
Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...
3.6K
03:00Preparation of Epoxides
8.8K
Overview
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy acids to...
8.8K
01:07Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.5K
In the presence of an aqueous base and a halogen, primary amides can lose the carbonyl (as carbon dioxide) and undergo rearrangement to form primary amines. This reaction, called the Hofmann rearrangement, can produce primary amines (aryl and alkyl) in high yields without contamination by secondary and tertiary amines.
3.5K
00:51Base-Promoted α-Halogenation of Aldehydes and Ketones
4.0K
α-Halogenation of aldehydes and ketones is a reaction involving the substitution of α hydrogens with halogens in the presence of a base. The reaction begins with the abstraction of α hydrogen by the base to produce a nucleophilic enolate ion. This intermediate undergoes a subsequent nucleophilic substitution with the halogen to produce a monohalogenated carbonyl compound. If the starting substrate has more than one α hydrogen, it is difficult to stop the reaction...
4.0K
01:19Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
522
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
522
01:33Radical Halogenation: Stereochemistry
4.3K
Stereochemistry is the study of the different spatial arrangements of atoms in a given molecule. The stereochemistry of radical halogenations can be understood from three different situations:
Halogenation to form a new chiral center:
Halogenation to form a new chiral center:
4.3K