Liquid-Phase Total Synthesis of Plecanatide Aided by Diphenylphosphinyloxyl Diphenyl Ketone (DDK) Derivatives
journal contributionposted on 10.04.2020, 19:45 by Haidi Li, Jie Chao, Zixin Zhang, Guang Tian, Jun Li, Ninghui Chang, Chuanguang Qin
Plecanatide is an oral guanylate cyclase-C agonist for the treatment of gastrointestinal disorders. The large-scale supply of plecanatide is restrained primarily by its industrial manufacture. Herein we developed diphenylphosphinyloxyl diphenyl ketone (DDK) derivatives as greener supports with unique precipitation-inducing properties to aid the liquid-phase total synthesis of plecanatide without the use of chromatography. Plecanatide could be obtained in high yield, and the ultimately sheared DDK derivative residue could be directly recycled or regenerated for reuse.