Nucleic Acid Related Compounds. 39. Efficient Conversion of 5-Iodo to 5-Alkynyl and Derived 5-Substituted Uracil Bases and Nuleosides

Article abstract of DOI:10.1021/jo00159a012

Coupling of terminal alkynes with 5-iodo-1-methyl-uracil and 5-iodouracil nucleosides (protected as their p-toluyl esters) proceeded in high yields in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I)iodide in warm triethylamine.Several of the subsequently deprotected 5-alkynyl-2'-deoxyuridines, including the parent 5-ethynyl-2'-deoxyuridine, had antiviral activity, and their 5'-monophosphates inhibited thymidylate synthetase.Hydrogenation of the 5-alkynyl side chain can be controlled to give (Z)-5-alkenyl- or the saturated 5-alkyl-2'-deoxyuridines.This provides a stereocontrolled route to the known 5-ethyl-and 5-n-hexyl-2'-deoxyuridines as well as (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU).Hydration of the triple bond gave the corresponding uracil-5-alkanone products in favorable cases.