Direct Synthesis of Aryloxy Phosphonamidate Nucleotide Prodrugs Using the Cross Metathesis Assisted by Ultrasonic Irradiation

• DOI: 10.1021/acs.orglett.4c00094
• Publication Date: 2024-02-21T17:36:21Z
• Authors: Se Myeong Choi; Ye Eun Nam; Yeon Jin An; Eun Rang Choi; Hyejin Park; Raymond F. Schinazi; Jong Hyun Cho

A direct synthetic strategy of aryloxy phosphonamidate nucleotide prodrugs (A, G, C, and U) was developed with the CM reaction assisted by ultrasonic irradiation partitioned addition 12 mol % Hoveyda–Grubbs (H-G) II catalyst in 61–82% yields as a mixture E-/Z-isomers (∼2:1) from vinylphosponamidate 5′-vinyl nucleoside moieties.