Optimization synthesis of phosphorous-containing natural products fosmidomycin and FR900098

Abstract

Fosmidomycin and its acetyl analogue FR900098 are two phosphorus-containing natural products with inhibitory activity against IspC enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis in plants and most bacteria. This work presents a facile route for the chemical synthesis of fosmidomycin and FR900098 using readily available raw materials. Through optimizing reaction conditions of the key steps of Michaelis-Becker reaction and acylation, the monosodium salts of fosmidomycin and FR900098 were obtained in yields of 60% and 66%, respectively, over six steps in the route. This unified route provides an alternative to the reported methods and makes it possible to synthesize the two valuable compounds with scalability and low cost, having the potential for application in developing new antimalarial drugs and pesticides.

Graphical Abstract

Keywords:

• IspC enzyme
• inhibitor
• fosmidomycin
• FR900098
• synthesis
• Michaelis-Becker reaction

Acknowledgements

The authors gratefully acknowledge the financial supports from the National Natural Science Foundation of China (No. 21772060 and 22277038).

Disclosure statement

The authors report there are no competing interests to declare.