Details

Autor(en) / Beteiligte

• Western, Elizabeth C
• Daft, Jonathan R
• Johnson, Edward M
• Gannett, Peter M
• Shaughnessy, Kevin H

Titel

Efficient One-Step Suzuki Arylation of Unprotected Halonucleosides, Using Water-Soluble Palladium Catalysts

Ist Teil von

• Journal of organic chemistry, 2003-08, Vol.68 (17), p.6767-6774

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.