Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside

The vinyl phosphonate derivatives of uridine, cytidine, and cytosine arabin oside (ara-C) have been prepared through oxidation of appropriately protect ed nucleosides to the 5' aldehydes and Wittig condensation with [(diethoxyp hosphinyl)methylidine]triphenylphosphorane. Dihydroxylation of these vinyl phosphonates with an AD-mix reagent generated the new 5',6'-dihydroxy-6'-ph osphonates. After hydrolysis of the phosphonate esters and the various prot ecting groups, the six phosphonic acids were tested for their ability to se rve as substrates for the enzyme nucleotide monophosphate kinase and for th eir toxicity to K562 cells. (C) 2000 Elsevier Science Ltd. All rights reser ved.