ja9b06050_si_001.pdf (20.04 MB)
New Catalytic Asymmetric Formation of Oxygen Heterocycles Bearing Nucleoside Bases at the Anomeric Carbon
journal contribution
posted on 2019-06-13, 00:00 authored by Barry M. Trost, Shiyan Xu, Ehesan U. SharifPyrimidine
nucleosides are an important class of compounds with
versatile applications across many fields, including biology and medicinal
chemistry. Synthesis of nucleoside analogs in optically pure form
via traditional glycosylation has always been a challenge, especially
for unnatural carbohydrate motifs which do not have C2 substitution
to dictate the stereochemical outcome of the newly formed glyosidic
bond. Herein, we report an asymmetric Pd-catalyzed synthesis of nucleoside
analogs enabled by the development of a series of chiral ligands.
A variety of 5-substituted pyrimidine nucleobases, ranging from 5-
to 12-membered ring nucleoside analogs, are generated in excellent
yield (up to 96%) as well as diastereo- (>20:1) and enantioselectivity
(up to 99.5% ee). These nucleoside analogs bearing an iodide functional
group handle allow for rapid transformation to a variety of other
interesting pyrimidine nucleoside structures.