Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside.
The vinyl phosphonate derivatives of uridine, cytidine, and cytosine arabinoside (ara-C) have been prepared through oxidation of appropriately protected nucleosides to the 5' aldehydes and Wittig condensation with [(diethoxyphosphinyl)methylidine]triphenylphosphorane. Dihydroxylation of these vinyl phosphonates with an AD-mix reagent generated the new 5',6'-dihydroxy-6'-phosphonates. After hydrolysis of the phosphonate esters and the various protecting groups, the six phosphonic acids were tested for their ability to serve as substrates for the enzyme nucleotide monophosphate kinase and for their toxicity to K562 cells.
Jung
K Y
KY
Department of Chemistry, University of Iowa, Iowa City 52242-1294, USA. kyjung@knusun.kangnung.ac.kr
Hohl
R J
RJ
Wiemer
A J
AJ
Wiemer
D F
DF
D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis*; D002625:Chemistry, Organic; D003561:Cytarabine / Q000138:chemical synthesis*; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D055601:Organic Chemistry Phenomena; D063065:Organophosphonates / Q000737:chemistry*; D011770:Pyruvate Kinase / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D000964:Antimetabolites, Antineoplastic; D063065:Organophosphonates; D003561:Cytarabine; D003562:Cytidine; D011770:Pyruvate Kinase; D014529:Uridine