Synthesis using ring closure metathesis and effect on nucleoside transport of a (N)-methanocarba S-(4-nitrobenzyl)thioinosine derivative.
[reaction: see text] A new synthetic route to ring-constrained (N)-methanocarba nucleosides and nucleotides is presented. Ring closure of a diene intermediate using Grubbs catalyst provides a new avenue for the preparation of the cyclopentenone derivative 6, which is a versatile intermediate for various carbocycles. The product was almost as potent an inhibitor of es-mediated nucleoside transport as the parent compound, inhibiting initial rates of uptake of uridine into cultured CCRF-CEM cells by 50% at approximately 30-50 nM.
Lee
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K
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cass
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C
Jacobson
K A
KA
D001692:Biological Transport / Q000187:drug effects*; D002384:Catalysis; D002478:Cells, Cultured; D003500:Cyclization; D003517:Cyclopentanes / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D009711:Nucleotides / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000737:chemistry
D003517:Cyclopentanes; D009711:Nucleotides; C007201:cyclopentanone; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine