Scientists from the Scripps Research Institute have developed an innovative method that allows, for the first time ever, the efficient production of a molecular skeleton common to a wide variety of compounds that exist in nature. This development provides effective tools for examining the potential of this molecular structure in the search for new drugs.
The aforementioned structure, known as "skipped polyenes", or conjugated polyenes (The entry in Wikipedia), shared by a large family of rodents that has an essential role in human health, including unsaturated fatty acids, which are essential for regulating blood pressure, inflammation and immune response. The structure is also present in a number of antibiotics, antifungals and other compounds that are toxic to humans.
For the most part, there are no simple and effective methods for preparing this structural skeleton, a fact that creates a significant limitation for testing its ability to be used in effective drugs. Today, the preparation of preparations containing simple derivatives of this structure is a task that requires quite a lot of effort.
"In our research we have identified a new chemical reaction that will allow the production of this type of structural motif to be accelerated," said Professor Glenn Micalizio. "This new reaction provides a tool for examining the medical potential of compounds containing complex conjugated polyanes - compounds that we simply have not been able to synthesize to date."
Essentially, the new chemical method provides a means to replace the long, multi-step sequence of reactions used today to prepare this structure. The new chemical process defines an innovative basic route - a new process for creating carbon-carbon bonds - for the production of these complex structures obtained after a small number of chemical steps.
As a result, the new method not only saves time, but significantly improves the efficiency of the preparation of compounds containing this structural skeleton. In chemistry, each of the steps (or reactions) used to prepare a complex structure progress, usually, with a utilization of less than one hundred percent (only 90-80 percent) relative to the amount of starting materials. As a result, the requirement for a long sequence of reactions (multi-step synthesis), where the utilization of each and every step is multiplied by the one after it (90 percent of 80 percent of 70 percent, etc.), causes a small final utilization to be obtained. "If it is possible to develop a sequence of reactions with a smaller number of steps for the preparation of complex structures, then we will be able to obtain a significant improvement in the efficiency of the reaction," explains the researcher. "One of the main issues in our lab focuses on designing new chemical reactions that do exactly that. Since 2005, we have been able to develop a large family of chemical reactions that can be called "chemical shortcuts" - so that ultimately scientists will be able to better test the medical potential of compounds containing diverse and extensive structures found in nature."
The new method, described in the article, progresses by the formation of a bond between two certain types of compounds: vinylcyclopropanes and alkynes, with the help of a metal-based cross-coupling reaction.
"This initial metal-based coupling leads to a highly unstable intermediate," said the researcher. "In fact, the chemical intermediate reorganizes independently into a stable structure, through a process that establishes the entire complex structure of the final product."
