This invention describes a one-pot process to synthesize chroman derivatives (formula I) by reacting salicylaldehyde (formula II), styrene derivatives (formula III), and trimethyl orthoformate with a Lewis/Bronsted acid and an organic solvent, forming an intermediate (formula IV). This intermediate then reacts with aryl nucleophiles (formula V) to yield the final chroman derivatives. Additionally, it outlines an efficient method for the total synthesis of myristinins A-F, enhancing the speed, scope, and scalability of producing these biologically important compounds.
Figure (1) formula (I) comprising reacting salicylaldehyde of formula (II) with styrene derivatives of formula (III) and trimethyl orthoformate in presence of Lewis/Bronsted acid and organic solvent to form an in-situ intermediate of formula (IV) followed by reaction with aryl nucleophiles of formula (V) to obtain the chroman derivatives of formula (I). The invention further relates to efficient total synthesis of Myristinins A -F.
Current methods for synthesizing flavonoids, particularly chroman derivatives and myristinins, are complex, time-consuming, and inefficient. These processes require multiple steps and specialized conditions, making it difficult to produce these biologically important compounds quickly and at scale. There's a need for a more straightforward, faster, and scalable method to synthesize these compounds effectively.
- One-pot Process for Chroman Synthesis: Utilizes a streamlined one-pot method combining salicylaldehyde, styrene derivatives, and trimethyl orthoformate with Lewis/Bronsted acid, reducing synthesis time and complexity, which facilitates quicker and more efficient production of valuable chroman derivatives.
- Comprehensive Total Synthesis of Myristinins A-F: Implements a direct synthesis approach using specific starting materials and hydrogenation steps, enabling a more straightforward and reliable production process for myristinins, which are important for their bioactive properties.
- Employment of Lewis/Bronsted Acids: Uses effective catalysts like Bi(OTf)3 and Cu(OTf)2, which improve reaction specificity and efficiency, resulting in higher yields and purer products, crucial for industrial applications requiring precision.
- Scalable and Adaptable Substrate Scope: Adapts to a wide range of substrates and scalable reaction conditions, allowing for the synthesis of various chroman derivatives and myristinins in larger quantities, meeting commercial and research demands.
- Mild Reaction Conditions: Conducts reactions at temperatures ranging from 0°C to room temperature with solvents such as acetonitrile and methanol, promoting safer and more environmentally friendly chemical processes.
- High Diastereoselectivity: Achieves moderate to high diastereoselectivity favoring the cis isomer, ensuring the production of specific desired isomers, which is critical for applications in pharmaceuticals where the configuration impacts biological activity.
- Simplified Purification Process: Utilizes straightforward chromatography techniques for purification, streamlining the isolation of pure compounds, thereby enhancing the overall efficiency and effectiveness of the synthesis process.
A functional laboratory-scale prototype has been demonstrated, utilizing a one-pot reaction system combining salicylaldehyde, styrene derivatives, and trimethyl orthoformate with Lewis/Bronsted acids. This setup efficiently produces chroman derivatives and myristinins under mild conditions. The system validates the process design and confirms its applicability to pharmaceutical synthesis.
The basic principles have been observed and reported. The process has been successfully developed at the laboratory level, with supporting data demonstrating its feasibility.
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- Enhanced Pharmaceutical Development: Facilitates the synthesis of bioactive compounds like myristinins, potentially leading to new treatments for diseases such as cancer and malaria.
- Accelerates Drug Discovery: Provides a faster, more reliable synthesis process, speeding up the availability of new medications for public health.
- Improves Healthcare Outcomes: Contributes to the development of potent therapeutic agents, enhancing treatment options and patient care.
- Economic Benefits: Reduces manufacturing costs and time in pharmaceutical production, leading to more affordable medications.
Pharmaceuticals, Organic chemistry, Medicinal Chemistry, Drug development, Bioactive compounds, Synthetic chemistry, Natural product synthesis
Geography of IP
Type of IP
202121026202
464585