(6S)-6-Fluoroshikimic acid

(6S)-6-Fluoroshikimic acid is a synthetic analog of shikimic acid, a key intermediate in the shikimate pathway. The shikimate pathway is a metabolic route used by bacteria, fungi, algae, parasites, and plants for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan), as well as other essential aromatic compounds like folates, quinones, and lignin precursors.

The introduction of a fluorine atom at the 6th position of the shikimic acid molecule results in (6S)-6-Fluoroshikimic acid. Fluorine substitution can significantly alter the biochemical properties of molecules due to the unique characteristics of the fluorine atom, such as its small size, high electronegativity, and strong carbon-fluorine bond.

(6S)-6-Fluoroshikimic acid acts as an inhibitor of the shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS catalyzes the penultimate step in the shikimate pathway, the condensation of phosphoenolpyruvate (PEP) and shikimate-3-phosphate (S3P) to form 5-enolpyruvylshikimate-3-phosphate (EPSP). Inhibition of EPSPS by (6S)-6-Fluoroshikimic acid disrupts the production of aromatic amino acids and other downstream metabolites, ultimately leading to growth inhibition or cell death in organisms that rely on the shikimate pathway.

Because animals do not possess the shikimate pathway, compounds that target this pathway are often considered relatively non-toxic to them, making (6S)-6-Fluoroshikimic acid and related compounds of interest in the development of herbicides and antimicrobial agents. Research involving (6S)-6-Fluoroshikimic acid has contributed to understanding the mechanism of action of EPSPS and the development of glyphosate, a widely used herbicide that also inhibits EPSPS. It has also been studied for potential applications as a novel antimicrobial agent.