Trost BM.
*
Xu S,
Sharif EU.
Stanford University, USA
New Catalytic Asymmetric Formation of Oxygen Heterocycles Bearing Nucleoside Bases at the Anomeric Carbon.
J. Am. Chem. Soc. 2019;
141: 10199-10204
Key words
pyrimidine nucleoside analogs - oxygen heterocycles - iodoetherification
Significance
Many FDA approved antiviral and anticancer drugs contain nucleoside analogs. The biologically active nucleosides are synthesized either by derivatization of an intact nucleoside or by coupling a nitrogenous base with a modified sugar (glycolsylation reaction). However, all previous methods suffered from poor yields and low diastereoselectivities.
Comment
Trost and co-workers reported a new Pd-catalyzed synthesis of pyrimidine nucleoside analogs bearing an iodide substituent. This process occurs in high yields as well as excellent enantio- and diastereoselectivity (dr >20:1). The products can be transformed into a variety of new pyrimidine nucleoside analogs. According to the proposed mechanism, the reaction proceeds through a Pd(IV) species, which undergoes reductive elimination to form a C–I bond.
