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Usage

Uses

Used in Pharmaceutical Industry:
cis-Atovaquone is used as an antimalarial agent for its ability to disrupt the electron transport chain in Plasmodium parasites, which are responsible for causing malaria. This action leads to the inhibition of parasite growth and the treatment of the disease.
Used in Antifungal Applications:
In the field of antifungal treatment, cis-Atovaquone is utilized as an antifungal agent, particularly effective against opportunistic fungal infections. Its mechanism of action targets the mitochondrial function in fungi, thereby inhibiting their growth and aiding in the treatment of various fungal infections.
Used in Research and Development:
cis-Atovaquone is also used as a research compound for studying the effects of mitochondrial electron transport inhibition on cellular processes and the development of new therapeutic strategies against various diseases, including cancer and other parasitic infections.

Upstream product

• 83-72-7 2-hydroxynaphtho-1,4-quinone 
• 1010-60-2 2-chloro-1,4-naphthoquinone 
• 1071223-07-8 cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone 
• 1203609-10-2 cis-2-[4-(4-chlorophenyl)cyclohexyl]-1,4-naphthoquinone 
• 1409957-42-1 cis-1a-(4-(4-chlorophenyl)cyclohexyl)naphtho[2,3-b]oxirene-2,7(1aH,7aH)dione 
• 94015-53-9 atovaquone 

Downstream Products

• 95233-18-4 atovaquone 

Relevant academic research and scientific papers

Late-Stage C-H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

Under oxidative conditions, 1,4-dihydropyridines (DHPs) undergo a homolytic cleavage, forming exclusively a Csp3-centered radical that can engage in the C-H alkylation of heterocyclic bases and 1,4-quinones. DHPs are readily prepared from aldehydes, and considering that aldehydes normally require harsh reaction conditions to take part in such transformations, with mixtures of alkylated and acylated products often being obtained, this net decarbonylative alkylation approach becomes particularly useful. The present method takes place under mild reaction conditions and requires only persulfate as a stoichiometric oxidant, making the procedure suitable for the late-stage C-H alkylation of complex molecules. Notably, structurally complex pharmaceutical agents could be functionalized or prepared with this protocol, such as the antimalarial Atovaquone and antitheilerial Parvaquone, thus evidencing its applicability. Mechanistic studies revealed a likely radical chain process via the formation of a dearomatized intermediate, providing a deeper understanding of the factors governing the reactivity of these radical forebears.

A single-pot synthesis of atovaquone: An antiparasitic drug of choice

The present article relates to a practical, economically viable, and validated at industrial scale, single-pot synthetic route for preparation of atovaquone, one of the most versatile antiparasitic drugs of choice used for the prophylaxis and treatment of diseases such as pneumocystis, toxoplasmosis, babesiosis, coccidiosis, and malaria. However, owing to the extremely poor yields of synthesis and very high doses of treatment (due to poor bioavailability) the cost of treatment with this drug is not affordable by the patients in need, particularly in the third world countries where these diseases are most prevalent. Unlike most of the reported processes which use 2-chloronaphthoquinone and pure trans-4-chlorophenyl cyclohexane carboxylic acid, our process is based on the decarboxylative alkylation of isomeric mixture of 4-chlorophenyl cyclohexane carboxylic acid with 1,4-naphthoquinone to give 42% overall yield of atovaquone, 10 times higher than from the reported process (4%) from the innovators of this drug.

NOVEL METHOD FOR PREPARATION OF ATOVAQUONE

Provided is a process of preparation of 2-[trans,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy- 1,4-naphthoquinone, i.e. Atovaquone [I] which is cost effective, green, and eco-friendly process, without separation of any diastereomers or geometric isomers of intermediates obtained during the reactions. Also provided is separation of 'cis' and 'trans ' isomer of intermediates VI, VII and VIII through selective crystallization in an appropriate solvent. A method for converting 2-[cis,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone to 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone in presence of Lewis/ Bronsted acid is also provided. A process for preparation of compound 2-(4-(4- chlorophenyl)- 1 -hydroxy cyclohexyl)-3,4-dihydronaphthalen- 1 (2H)-one [IV] comprising condensation of (1,2-dihydronaphthalen-4-yloxy)trimethylsilane [II] with 4-(4- chlorophenyl)cyclohexanone [III] in presence of Lewis acid in organic solvent. The invention also encompasses a highly efficient and atomeconomic process for synthesis of compound [III] i.e. 4-(4-chlorophenyl)cyclohexanone as well as a process for synthesis of 2-[cis-4-(4'- chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone. Further provided is a process for isomerization of cis- Atovaquone i.e. 2-[cis-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4- naphthoquinone to tnms-Atovaquone i.e. 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3- hydroxy- 1,4-naphthoquinone in presence of Lewis acid.