Washington, April 16 (Inditop) Club moss Lycopodium serratum is a flowerless plant whose potent brew of alkaloids, which could have anti-cancer properties and may combat memory loss, have drawn considerable scientific and medical interest. Now scientists have made one of the alkaloids in a lab, in quantity sufficient for use.
However, the plant makes many of these compounds in extremely low amounts, hindering efforts to test their therapeutic value.
That is no longer a problem for what is arguably the most complex of these alkaloids, a compound called Serratezomine A: an alkaloid that could have anti-cancer properties and may tackle memory loss.
A team of synthetic chemists at Vanderbilt University reported that they have created an efficient way to make this molecule from scratch. It took six years to develop the process because the researchers had to invent some entirely new chemical methods to complete the synthesis.
These methods should make it easier to synthesise other Lycopodium alkaloids as well as other natural compounds with therapeutic potential.
Besides therapeutic possibilities, Vanderbilt chemists were attracted to these compounds because they are among the most intricately structured and functionally dense of all the small molecules produced by living organisms. The compounds consist of carbon and nitrogen atoms assembled in unique ring structures.
“This was a challenging problem,” said Jeffrey Johnston, a chemistry professor who led the research. “It takes years to develop a new chemical reaction and then apply it to the natural product target. So, once we start, we don’t stop.”
In the world of total synthesis chemistry, it is not enough to figure out a way to synthesise a naturally occurring molecule, said a Vanderbilt release.
The process has to produce large enough quantities of the molecule that it can be tested for biological activity. That means that the number of sequential steps in the process – what chemists refer to as the longest linear sequence – should be as small as possible to maximise production.
For example, if a sequence has 30 steps and each step has an 80 percent yield, the overall yield of the sequence is about a tenth of one percent. At the same time, one low-yield step will knock a process out of contention.
These findings was published in the March 18 issue of the Journal of the American Chemical Society.
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