Acetylenic nucleosides. 3. Synthesis and biological activities of some 5-ethynylpyrimidine nucleosides.
Iodination of 1-(2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)uracil furnished the 5-iodo derivative (Ib), which, on treatment with (trimethylsilyl)acetylene in the presence of catalytic amounts of (Ph3P)2PdCl2/CuI and subsequent deblocking, afforded 1-beta-D-arabinofuranosyl-5-ethynyluracil (Ie). Condensation of the trimethylsilyl derivative of 5-(dibromovinyl)uracil with 3-O-acetyl-5-O-benzoyl-2-deoxy-2-azido-D-arabinofuranosyl chloride, followed by treatment with phenyllithium, gave 1-(2-deoxy-2-azido-beta-D-arabinofuranosyl)-5-ethynyluracil (IIb). Condensation of 3-O-acetyl-5-O-benzoyl-2-deoxy-2-fluoro-D-arabinofuranosyl bromide with the trimethylsilyl derivative of 5-ethynylcytosine and subsequent removal of the protecting groups furnished 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethynylcytosine (IIIb). The structural assignment for IIb and IIIb was made by NMR and ORD spectra. Compounds Ie and IIIb inhibited the growth of leukemia L-1210 cells in culture by 50% at concentrations of 1.7 X 10(-5) and 6 X 10(-5) M, respectively. In addition, Ie and IIIb inhibited the replication of herpes simplex virus type I by 90% at concentrations of 2.8 X 10(-5) and 5 X 10(-5) M, respectively. Compound IIb did not show any antileukemic or antiherpes activity.
D000107:Acetylation; D000480:Alkynes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects
D000480:Alkynes; D011741:Pyrimidine Nucleosides