The Power of Synthetic Molecules: Creating Lissodendoric Acid A

Organic chemists at UCLA have recently created the first synthetic version of a molecule found in a sea sponge that may have therapeutic benefits for Parkinson’s disease and similar disorders. The molecule, known as lissodendoric acid A, appears to counteract other molecules that can damage DNA, RNA, and proteins and even destroy whole cells. By using an unusual, long-neglected compound called a cyclic allene, the research team was able to control a crucial step in the chain of chemical reactions needed to produce usable versions of this molecule. This advance could prove advantageous in developing other complex molecules for pharmaceutical research.

Chirality: A Key Factor in Synthetic Organic Molecules

One of the challenges in creating synthetic organic molecules is chirality, or “handedness.” Many molecules, including lissodendoric acid A, can exist in two distinct forms that are chemically identical but are 3D mirror images of each other, like a right and left hand. Each version is known as an enantiomer. When used in pharmaceuticals, one enantiomer of a molecule may have beneficial therapeutic effects while the other may do nothing at all or even prove dangerous. Unfortunately, creating organic molecules in the laboratory often yields a mixture of both enantiomers, and chemically removing or reversing the unwanted enantiomers adds difficulties, costs, and delays to the process.

Cyclic Allenes: A Solution to the Challenge

To address this challenge and quickly and efficiently produce only the enantiomer of lissodendoric acid A that is beneficial, the UCLA research team employed cyclic allenes as an intermediate in their 12-step reaction process. First discovered in the 1960s, these highly reactive compounds had never before been used to make molecules of such complexity. The team discovered that they could harness the compounds’ unique qualities to generate one particular chiral version of cyclic allenes, which in turn led to chemical reactions that ultimately produced the desired enantiomer of the lissodendoric acid A molecule almost exclusively.

The Future of Synthetic Molecules

While the ability to synthetically produce an analog of lissodendoric acid A is the first step in testing whether the molecule may possess suitable qualities for future therapeutics, the method for synthesizing the molecule is something that could immediately benefit other scientists involved in pharmaceutical research. “By challenging conventional thinking, we have now learned how to make cyclic allenes and use them to make complicated molecules like lissodendoric acid A,” said Neil Garg, UCLA’s Kenneth N. Trueblood Professor of Chemistry and Biochemistry and corresponding author of the study. “We hope others will also be able to use cyclic allenes to make new medicines.”


What is chirality?

Chirality is a property of molecules that describes their handedness or 3D mirror image. Many molecules can exist in two different forms that are chemically identical but have different therapeutic effects.

What are cyclic allenes?

Cyclic allenes are highly reactive compounds that were first discovered in the 1960s. They have unique qualities that make them useful in generating chiral versions of complex molecules.

How can the UCLA research team’s discovery benefit pharmaceutical research?

The UCLA research team’s discovery of using cyclic allenes to create chiral versions of complex molecules could benefit pharmaceutical research by making the process of synthesizing molecules quicker, more efficient, and more affordable. This could lead to the development of new medicines for various diseases and disorders.

Posted in