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

Org Lett. 2024 Feb 21. doi: 10.1021/acs.orglett.4c00094. Online ahead of print.

Abstract

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