Biomimetic synthesis of natural products: Progress, challenges and prospects

In a recent publication in Engineering, researchers from Jinan University in China and the University of Illinois Chicago in the US presented an in-depth perspective on the biomimetic synthesis of natural products. This research area, which bridges chemistry, biology, and pharmacy, has seen significant progress in recent years.

Natural products are crucial in drug discovery, providing essential scaffolds for developing new medications. However, obtaining sufficient quantities of these compounds for research and production is challenging due to resource limitations. Traditional chemical synthesis and biosynthesis methods also face their own set of problems, such as high reagent costs, environmental unfriendliness, and limitations in modifying complex molecules.

Biomimetic synthesis offers a promising alternative. It imitates the biosynthetic processes in nature to design synthetic strategies for natural products. This approach dates back to the late 19th century, with significant milestones including Robinson’s synthesis of tropinone in 1917. Since then, various biomimetic strategies have been developed.

For instance, the biomimetic polyene cyclization strategy mimics the natural process of creating complex cyclic structures from polyene precursors. It has been used to synthesize steroids like progesterone and terpenoid alkaloids, providing insights into stereoselective control. The biomimetic oxidative coupling strategy, which imitates the oxidative joining of phenol or indole units, has been applied in the synthesis of morphine-like molecules and natural phenolic products. The biomimetic Diels-Alder reaction strategy, inspired by the natural cycloaddition process, has enabled the synthesis of complex polycyclic rings in natural products such as FR182877.

Despite these advances, biomimetic synthesis still faces challenges. Synthesizing natural products with multiple chiral centers and unique functional groups requires sophisticated techniques. Many biomimetic reactions have low yields or side reactions, and it’s difficult to develop routes using easily accessible starting materials. Scaling up from laboratory-scale to industrial-scale production is also a major hurdle.

Looking ahead, the prospects of biomimetic synthesis are promising. It can create complex natural products and their derivatives, expanding the molecular library for drug research. Integrating chemical and biological synthesis, along with the development of new strategies, will further enhance the efficiency of production. Additionally, the use of big data and deep learning technologies could optimize synthetic routes and improve predictability.

The paper “Strategies and Advances in the Biomimetic Synthesis of Natural Products,” authored by Li-Jun Hu, Zhi-Zhang Duan, Ying Wang, Wen-Cai Ye, Chun-Tao Che. Full text of the open access paper: https://doi.org/10.1016/j.eng.2024.12.013. For more information about the Engineering, follow us on X (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringJrnl).

END