R-2-(4-Hydroxyphenoxy) Propionic Acid: Technological Innovation from Chemical Synthesis to Green Biological Manufacturing

With the increasing demand for green manufacturing and sustainable development, the synthesis process of R-2-(4-hydroxyphenoxy) propionic acid is undergoing a profound change from traditional chemical method to green biological method. The conventional chemical synthesis route starts with L-lactic acid and involves three sequential steps: esterification, sulfonylation, and etherification. This approach can achieve an optical purity of 97.9% or higher; however, the synthetic pathway is relatively long, and certain steps present challenges in controlling stereoinversion.
In recent years, major breakthroughs have been made in biocatalytic synthesis routes. A deep-tank fermentation process using the entomopathogenic fungus Beauveria bassiana strain ZJB23323 as the production strain was optimized by supplementing the medium with soybean oil and phase-transfer catalysts (such as cyclodextrins, tetrabutylammonium bromide, and polyethylene glycol 1000) and employing a fed-batch co-cultivation strategy, which markedly enhanced the fermentation yield of R-2-(4-hydroxyphenoxy)propionic acid. Compared with chemical synthesis, biocatalytic methods offer several distinct advantages, including mild reaction conditions, high stereoselectivity, minimal byproduct formation, and greater environmental friendliness. Meanwhile, the process for isolating and purifying DHPPA from the fermentation broth has been continuously optimized. By employing techniques such as heat-induced solid–liquid separation, extraction under different pH conditions, filtration, and recrystallization, the product purity can reach over 90%, with an average yield of 85% to 95%. Furthermore, the grant of a patent for a new purification device has significantly enhanced both the mixing rate of the raw material and solvent, as well as crystal purity. These breakthroughs in green processes have laid a solid foundation for the large-scale, clean production of DHPPA.