Document Report Card

ID: ALA1125887

Journal: J Med Chem

Title: Nucleosides and nucleotides. 94. Radical deoxygenation of tert-alcohols in 1-(2-C-alkylpentofuranosyl) pyrimidines: synthesis of (2'S)-2'-deoxy-2'-C-methylcytidine, an antileukemic nucleoside.

Authors: Matsuda A, Takenuki K, Sasaki T, Ueda T.

Abstract: (2'S and 2'R)-2'-Deoxy-2'-C-methylcytidine (1i and 15) and (2'S)-2'-deoxy-2'-C-ethylcytidine (1j) have been synthesized from the corresponding 2'-C-alkylarabinofuranosyl- or -ribofuranosylpyrimidine derivatives 3 and 4 by radical deoxygenation of the methyl oxalyl esters of the 2'-tert-alcohol, followed by sequential deblocking and amination at the 4-position. (2'S)-2'-Deoxy-2'-C-methyl-5-methyluridine (8) has also been synthesized in a similar manner. Among them, compound 1i exhibits the most potent cytotoxicity to L1210 cells with potency comparable to that of 1-beta-D-arabinofuranosylcytosine (1a). The size of the 2'-substituents and the configuration at the 2'-position are the most important for the cytotoxicity. Cytotoxicity in vitro of 1i against various human cancer cell lines was also examined and compared with that of 1a and 5-fluorouracil.

CiteXplore: 1992123

DOI: 10.1021/jm00105a037