Scientists from The Scripps Research Institute claim to have created for the first time a technique that will permit proficient production of molecular structures known as skipped polyenes. These are shared by a huge class of molecules and are said to be common to a vast range of natural molecules. The potential of these molecular structures would assist in developing new therapies.
Skipped polyenes supposedly play an important role in human health and also include polyunsaturated fatty acids which are beneficial in blood pressure regulation, inflammation and immune response. These structures are shared by a number of antibiotic, antifungal and cytotoxic compounds. Generally, methods for the preparation of skipped polyenes that are efficient and simple have been lacking, posing a considerable barrier in maximizing their potential as drugs. The production of molecules that presently contain simple variants of this substructure is known to be quite labor intensive.
“Our study identifies a novel chemical reaction that will enable the accelerated production of this type of structural concept,” explained Associate Professor Glenn Micalizio, who authored the new study with a member of his Scripps Florida lab, study associate Todd K. Macklin. “This new reaction provides a means to explore the medicinal potential of molecules bearing complex skipped polyenes – something that we simply haven’t been able to do until now.”
The new chemical method reduces the steps required in forming skipped polyenes. This process defines an essential pathway towards these complex structures. They proceed in fewer steps than the chemical ones previously required. This new method not only saves time but also increases efficiency in production of these molecules according to the scientists.
“If one can invent reactions that decrease the length of sequences required to prepare complex structures, great enhancements of efficiency can result,” said Micalizio. “A central focus of our laboratory is designing new chemical reactions that do just that. Since 2005, we have been advancing a large class of chemical transformations that can be seen as ‘chemical short cuts’ so that ultimately scientists can better explore the therapeutic potential of molecules inspired by the vast and diverse structures that we see in nature.”
These molecules cover the skipped polyene core. Micalizio comments that in chemistry reactions for the formation of molecules are not 100 percent efficient it is assumed that 80-90 percent of previous material can be moved to the next chemical step. The necessities of long sequences of reactions, where the outputs of each step are mathematically compounded through the sequence results in reduced overall effectiveness.
“That initial metal-promoted coupling leads to a very unstable intermediate molecule,” Micalizio said. “Actually, the chemical intermediate spontaneously rearranges to stabilize the structure, through a process that establishes all of the complex architecture of the skipped polyene product.”
This new technique advances by bond development among two specific classes of molecules vinylcyclopropanes and alkynes. In order to assemble the key structure idea it uses a metal-promoted cross-coupling reaction.
This study was published on May 23, 2010 in an advance online edition of the journal Nature Chemistry.