Related Experiment Video
Updated: Nov 7, 2025
![Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60786.jpg&w=3840&q=50)
07:12
Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
6.4K
Synthesis of New Triazolopyrazine Antimalarial Compounds
Daniel J G Johnson1, Ian D Jenkins1, Cohan Huxley1
1Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, Australia.
Molecules (Basel, Switzerland)
|April 30, 2021
Summary
Researchers synthesized novel triazolopyrazine analogues using photoredox and Diversinate chemistry. Some analogues showed moderate antimalarial activity against Plasmodium falciparum without significant toxicity to human cells.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Parasitology
Background:
- The Open Source Malaria (OSM) project aims to develop new antimalarial drugs.
- Triazolopyrazine scaffolds are of interest for antimalarial drug discovery.
Purpose of the Study:
- To synthesize novel triazolopyrazine analogues via late-stage functionalization.
- To evaluate the antimalarial activity and cytotoxicity of the synthesized compounds.
Main Methods:
- Utilized photoredox and Diversinate chemistry for late-stage functionalization of the triazolopyrazine scaffold.
- Characterized new analogues using NMR, UV, MS, and X-ray crystallography.
- Assessed antimalarial activity against Plasmodium falciparum (3D7 and Dd2 strains) and cytotoxicity against HEK293 cells.
Main Results:
- Synthesized 12 new triazolopyrazine analogues.
- Confirmed structures of four analogues via X-ray crystallography.
- Observed moderate antimalarial activity (IC50: 0.3 to >20 µM) for some compounds.
- Demonstrated no significant cytotoxicity against HEK293 cells at 80 µM.
Conclusions:
- Novel triazolopyrazine analogues were successfully synthesized and characterized.
- Several analogues exhibit promising antimalarial activity with a good safety profile.
- This work contributes to the ongoing search for new antimalarial therapies.
Related Concept Videos
01:11Aryldiazonium Salts to Azo Dyes: Diazo Coupling
3.2K
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para...
3.2K
01:19Diazonium Group Substitution: –OH and –H
3.0K
Nitrous acid, a weak acid, is prepared in situ via the reaction of sodium nitrite with a strong acid under cold conditions. This nitrous acid prepared in situ reacts with primary arylamines to form arenediazonium salts. Such reactions are known as diazotization reactions. As shown in Figure 1, the formation of arenediazonium salts begins with the decomposition of nitrous acid in an acidic solution to give nitrosonium ions.
3.0K
01:28Preparation of 1° Amines: Gabriel Synthesis
4.0K
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
4.0K
01:07Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
3.4K
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.
3.4K
01:22Preparation of 1° Amines: Azide Synthesis
4.2K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
4.2K
01:20Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
2.1K
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
2.1K