An improved stereodivergent and practical synthesis of α- and β-pseudouridines

Abstract

An improved stereodivergent and practical synthesis of both α- and β-pseudouridines has been achieved from a common intermediate. This practical approach features a highly diastereoselective Grignard reaction using inexpensive protected D-ribose under non-cryogenic conditions and a divergent one-pot, acid-mediated global deprotection–cyclisation and anomerization to give β-pseudouridine, or a Mitsunobu cyclisation followed by deprotection to provide α-pseudouridine. Detailed ¹H NMR kinetic studies provide insight into the cyclisation and anomerization steps.