Document Report Card

ID: ALA1125651

Journal: J Med Chem

Title: 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.

Authors: Matsuda A, Yasuoka J, Sasaki T, Ueda T.

Abstract: 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.

CiteXplore: 2002478

DOI: 10.1021/jm00107a018