Improvement of the <i>C</i>-glycosylation Step for the Synthesis of Remdesivir
Fei Xue, Xinbo Zhou, Ruijie Zhou, Xiaohan Zhou, Dian Xiao, Eric Gu, Xiaowen Guo, Ji Xiang, Ke Wang, Likai Yang, Wu Zhong, Yong Qin
Abstract
The bulk supply of the antiviral C-nucleoside analogue remdesivir is largely hampered by a low-yielding C-glycosylation step in which the base is coupled to the pentose unit. Here, we disclose a significantly improved methodology for this critical transformation. By utilizing diisopropylamine as a cost-effective additive, the addition reaction furnishes an optimal yield of 75% of the desired ribofuranoside adduct, representing the highest yield obtained thus far for this key step. The method proved suitable for hectogram scale synthesis without column chromatographic operations.
Topics & Concepts
Yield (engineering)GlycosylationChemistryNucleosideCombinatorial chemistryAdductStereochemistryOrganic chemistryBiochemistryMaterials scienceMetallurgyPneumocystis jirovecii pneumonia detection and treatmentHIV/AIDS drug development and treatmentPeptidase Inhibition and Analysis