Advantages
- Allows preservation the physical properties and pharmacological activity of starting materials
- Waste-free, environmentally adaptable, cost-effective process that requires only visible light and photocatalyst
- High yield with 1 step synthesis
- More than 10 kinds (average yield 90%) have already been synthesized
Background & Technology
Mitochondria are important organelles that play essential roles in the maintenance of life, such as energy production, induction and control of apoptosis, and regulation of calcium signaling. Drug delivery to mitochondria is essential. Quaternary phosphonium cations are cationic species in which four carbon substituents are substituted on the phosphorus atom, and are widely used for pharmaceuticals and functional materials, etc. Taking advantage of the localization of phosphonium cations in mitochondria, various phosphonium salt compounds are utilized in medical research targeting the mitochondria and in disease treatment (reviewed in Chem. Rev. 2017, 117, 10043).
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However, conventional methods for synthesizing phosphonium compounds use the functional groups of alkyl halides and amines, so the starting materials are limited, and the structures of the phosphonium compounds that can be synthesized are often restricted. Furthermore, in conventional methods, the phosphonium groups are introduced by converting the original functional groups, resulting in loss of the original physical properties and physiological activity of the starting materials. The inventors have now established a new synthetic method using only visible light (blue LED) and a photocatalyst (iridium catalyst), and have found that a vinyl phosphonium compound reacts with a versatile alcohol or amine to give a quaternary phosphonium compound by substituting carbon-hydrogen bonds.
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＊Left: X = Hydroxy or Amino group Right: iridium catalyst
Data
Examples of the introduction of phosphonium into drug molecules by this process and the scope of application are shown below.
＜Introduction of phosphonium to Bucetin＞
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＜Examples of applicable scope＞
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Researcher
Hokkaido University Graduate school of science, Organometallic Chemistry Lab.
Yusuke Masuda, Masaya Sawamura, Masaki Yoshida
Publication
Masaki Y. et al, ChemCatChem 2022, 14, e202200744
Patent
・Pending (unpublished)
Development Phase
This stage: Demonstration of phosphonium compound synthesis and confirmation of scope of application completed. Mechanistic research continues.
Next stage:
1. Verification of phosphonium introduction into desired substances
2. Evaluation of activity/performance and development demonstration of acquired agents
3. Industrialization of this process by establishing a mass production system
1 and 2 are available for collaboration research and development with our laboratory, and 3 is available for consideration by partner companies.
We are looking for partner companies interested in evaluating phosphonium compounds of target substances using this technology or in collaborations. We would be happy to start with a detailed explanation and discussion of the technology.
Project No. ON-04720