Alpha-phosphono lactone analogues of cytidine and cytosine arabinoside diphosphates: synthesis via ring closing metathesis.
alpha-Phosphono lactone derivatives of the nucleosides cytidine and cytosine arabinoside have been prepared from the corresponding nucleoside aldehydes. The stereochemical outcome of allylation reactions with these aldehydes was found to be dependent upon both the choice of protecting groups for the 2'- and 3'-hydroxyl groups and, to some extent, the nature of the Lewis acid catalyst employed. Ultimately, conditions were found that favored either the 5'R or 5'S diastereomer from different cytidine aldehydes, and gave some stereoselectivity in additions to an aldehyde derivative of ara-C. The resulting homoallylic alcohols were used as substrates in attempted Knovenagel and Horner-Wadsworth-Emmons condensations, but elimination was found to predominate over lactone formation under the conditions employed. The desired alpha-phosphono lactones could be prepared through a reaction sequence that included ring-closing metathesis on acrylate esters of the homoallylic alcohols, followed by reduction of the resulting alpha,beta-unsaturated lactones and carbon-phosphorus bond formation on enolates generated from the saturated lactones.
Chen
Xuemei
X
Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, USA.
Wiemer
David F
DF
D001089:Arabinose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D003562:Cytidine / Q000031:analogs & derivatives / Q000737:chemistry*; D003565:Cytidine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents; D007783:Lactones; D008958:Models, Molecular; D063065:Organophosphonates; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007783:Lactones; D063065:Organophosphonates; D003561:Cytarabine; D003562:Cytidine; D003565:Cytidine Diphosphate; D003596:Cytosine; D001089:Arabinose