Covalent Modification of Nucleobases using Water‐Soluble Palladium Catalysts

Abstract

Nucleosides represent one of the key building blocks of biochemistry. There is significant interest in the synthesis of nucleoside-derived materials for applications as probes, biochemical models, and pharmaceuticals. Palladium-catalyzed cross-coupling reactions are effective methods for making covalent modification of carbon and nitrogen sites on nucleobases under mild conditions. Water-soluble catalysts derived from palladium and hydrophilic ligands, such as tris(3-sulfonatophenyl)phosphine trisodium (TPPTS), are efficient catalysts for a range of coupling reactions of unprotected halonucleosides. Over the past two decades, these methods have been extended to direct functionalization of halonucleotides, as well as RNA and DNA oligonucleotides (ONs) containing halogenated bases. These methods can be run under biocompatible conditions, including examples of Suzuki coupling of modified DNA in whole cells and tissue samples. In this account, development of this methodology by our group and others is highlighted along with the extension of these catalyst systems to modification of nucleotides and ONs.

Rapid plugged flow synthesis of nucleoside analogues via Suzuki-Miyaura coupling and heck Alkenylation of 5-Iodo-2’-deoxyuridine (or cytidine)

“…The introduction of aromatic or heteroaromatic functionalities on the nucleosides (that help enhance the fluorescent properties) via metal-catalyzed cross-coupling reactions [5,6] (especially palladium-catalyzed Suzuki-Miyaura coupling) has been extensively explored [7,8]. Contributions by the research groups of Len [9][10][11][12], Shaughnessy [13][14][15][16], Lakshman [17][18][19][20][21][22] and many others [18][19][20][21][22] are acknowledged for their advances in the area of nucleoside modification. We have also been active in the development of several catalytic systems (palladium-based) allowing efficient cross-coupling [23][24][25][26][27][28][29][30].…”