Experimental optimization and
validation of Burparvaquone
synthetic routes
By
Hazel Tatenda Chikukwa
BACKGROUND
Introduction
- Buparvaquone, a hydroxynaphthoquinone antiprotozoal agent, treats theileriosis in cattle,
sheep, goats, and buffalo
Mechanism of Action
-Buparvaquone inhibits parasite respiratory system activities
-Does not affect membrane permeability but it is able to irreversibly bind to cytochrome b in the
bc1 complex within mitochondria
Chemical Properties
- Molecular formula: C21H26O3
- Molecular mass: 326.436 g/mol
- Class: Hydroxyl naphthoquinones
- High hydrophobic compound ( Log P 6.5), small water soluble
Commercial Preparations
- Zubion
- Butalex
BACKGROUND
Treatment Regimen
- Dosage: 2.5 mg/kg body weight (intramuscular, parenteral)
- Frequency: Multiple injections over days or weeks (dependent on infection
severity)
Pharmacological Effects
- Effective in early stages of infection
- Decreased efficacy in later stages
Safety and Efficacy
- Pregnant cattle: decreased drug effectiveness
- Sheep: safe, with minor changes in troponin 1, blood urea nitrogen, and
alkaline phosphatase levels
- Buffalo: more effective in early stages
PROBLEM STATEMENT
The relatively high cost of Buparvaquone limits its
worldwide application, hindering access to effective
theileriosis treatment. To address this, previous
studies have proposed alternative synthetic routes.
However, the feasibility and yield optimization of
these routes remain unverified, necessitating
experimental optimization and validation.
Knowledge Gap
The feasibility, yield optimization, and validation of
alternative Buparvaquone synthesis methods remain
unverified, making it unclear whether these routes
can produce the drug efficiently and cost-effectively."
Justification
This study justifies the optimization of alternative
Buparvaquone synthesis methods to improve
accessibility, efficiency, and cost-effectiveness of
theileriosis treatment, ultimately enhancing livestock
health and economic stability.
AIM
To optimize and validate Buparvaquone
synthetic routes
OBJECTIVES
[Link] evaluate the feasibility of proposed synthetic
routes through laboratory synthesis
[Link] optimize proposed routes for improved yield and
efficiency.
[Link] validate the optimized synthetic routes by
comparing experimental yields with
reported/predicted yields.
RESEARCH QUESTIONS
Objective 1
1. What are the reaction conditions and reagents required for successful synthesis of Buparvaquone through the
proposed routes?
2. Do the proposed synthetic routes yield Buparvaquone with acceptable purity and recovery?
Objective 2
1. How do variations in reaction temperature, pressure, and solvent affect the yield and efficiency of
Buparvaquone synthesis?
2. Can modifications to the reaction sequence, catalysts, or reagents enhance the yield and efficiency of the
proposed synthetic routes?
Objective 3
1. Do the optimized synthetic routes consistently produce Buparvaquone with yields comparable to reported
literature values?
2. How do the experimental yields from optimized routes compare to predicted yields based on theoretical
calculations or modeling?
METHODOLOGY
Literature review : literature review on overview importance, properties , applications,
existing synthetic methods, optimization techniques, reaction conditions of Burparvaquone
Synthetic producers : synthesis method , reaction conditions eg temperature, pressure etc ,
catalyst
Chemicals :
Catalyst : Palladium catalyst
Optimization techniques: Use of OFAT( One factor - at a time technique) or DeO( Design of
Expriment) , use of HPLC to optimize the reaction conditions eg temperature etc ,
optimization of yield ( that's improving the yield)
Validation: Use of High Performance Liquid chromatography to validate the yield , purity and
product
Data Analysis: Use of statistical method eg R (
Results and Discussion
-Analyze results using statistical software( R or
Python )
- Compare optimized and standard synthesis
methods.
- Present findings using tables and graphs.
- Discussion will focus on how optimized reaction
conditions impacted yield and purity, interpreting the
presence and concentrations of impurities,comparing
of results to existing studies as well as
the implications of the achieved yield and purity.
ACTIVITY DURATION
Literature review 2 weeks
Synthesis process 4 weeks
Optimization 4weeks
Validation 4weeks
Data analysis 2weeks
Report writing 2weeks
Conclusion
This proposed research aims to optimize and validate
the Buparvaquone synthesis route, enhancing cost-
effectiveness, yield, and purity. Upon successful
completion, this project will contribute significantly
to the pharmaceutical industry and veterinary
medicine, improving treatment options and efficacy.
The anticipated outcomes will pave the way for
future research and development in antiprotozoal
drug synthesis