Efficient one-step Suzuki arylation of unprotected halonucleosides, using water-soluble palladium catalysts.
Modification of nucleosides to give pharmaceutically active compounds, mutagenesis models, and oligonucleotide structural probes continues to be of great interest. The aqueous-phase modification of unprotected halonucleosides is reported herein. Using a catalyst derived from tris(3-sulfonatophenyl)phosphine (TPPTS) and palladium acetate, 8-bromo-2'-deoxyguanosine (8-BrdG) is coupled with arylboronic acids to give 8-aryl-2'-deoxyguanosine adducts (8-ArdG) in excellent yield in a 2:1 water:acetonitrile solvent mixture. The TPPTS ligand was found to be superior to water-soluble alkylphosphines for this coupling reaction. The coupling chemistry has been extended to 8-bromo-2'-deoxyadenosine (8-BrdA) and 5-iodo-2'-deoxyuridine (5-IdU), as well as the ribonucleosides 8-bromoguanosine and 8-bromoadenosine. Good to excellent yields of arylated adducts are obtained in all cases. With use of tri(4,6-dimethyl-3-sulfonatophenyl)phosphine (TXPTS), the Suzuki coupling of 8-BrdA and 5-IdU can be accomplished in less than 1 h at room temperature. This methodology represents an efficient and general method for halonucleoside arylation that does not require prior protection of the nucleoside.
Western
Elizabeth C
EC
Department of Chemistry and the Center for Green Manufacturing, The University of Alabama, Box 870336, Tuscaloosa, Alabama 35487-0336, USA.
Daft
Jonathan R
JR
Johnson
Edward M
EM
Gannett
Peter M
PM
Shaughnessy
Kevin H
KH
D002384:Catalysis; D006151:Guanosine / Q000031:analogs & derivatives*; D007065:Idoxuridine; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds; D010165:Palladium; D013451:Sulfonic Acids
D007202:Indicators and Reagents; D009705:Nucleosides; D009943:Organophosphorus Compounds; D013451:Sulfonic Acids; C400058:triphenylphosphine-3,3',3''-trisulfonic acid; D006151:Guanosine; C035169:8-bromoguanosine; D010165:Palladium; D007065:Idoxuridine