Nucleosides and nucleotides. 95. Improved synthesis of 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)cytosine (cytarazid) and -thymine. Inhibitory spectrum of cytarazid on the growth of various human tumor cells in vitro.
Reaction of N3-benzoyl-1-[3,5-O-(tetraisopropyldisiloxan-1,3-diyl)-beta- D- ribofuranosyl]thymine (4a) with diphenyl phosphorazidate, diethyl azodicarboxylate, and triphenylphosphine in tetrahydrofuran afforded N3-benzoyl-1-[2-azido-2-deoxy-3,5-O- (tetraisopropyldisiloxan-1,3-diyl)-beta-D-arabinofuranosyl]t hymine (5a) in good yield. After the sequence of deblocking of 5a gave 1-(2-azido-2-deoxy-beta-D-arabinofuranosyl)thymine (7), it was heated in N,N-dimethylformamide to produce 6,2'-imino-1-(2-deoxy-beta-D-arabinofuranosyl)thymine (8). This reaction disclosed the arabino configuration for 5a. Similarly the N3-benzoyluracil derivative 4b was transformed to the corresponding 2'-"up"-azidouridine derivative 5b, which was further converted to 1-(2-azido-2-deoxy-1-beta-D-arabinofuranosyl)cytosine (1, cytarazid). The antineoplastic activity of 1 was compared with that of ara-C against various human cancer cell lines in vitro.
Matsuda
A
A
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Yasuoka
J
J
Sasaki
T
T
Ueda
T
T
D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors; D013274:Stomach Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D003561:Cytarabine; C067821:1-(2-azido-2-deoxyarabinofuranosyl)thymine; D015215:Zidovudine; C017163:cytarazid