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 INVITRO

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]thymine (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.