Synthesis and biological activity of 4'-C-hydroxymethyl-2'-fluro-D-arabinofuranosylpurine nucleosides.
A series of 4'-C-hydroxymethyl-2'-fluoro-D-arabinofuranosylpurine nucleosides was prepared and evaluated for cytotoxicity. The details of a convenient synthesis of the carbohydrate precursor 4-C-hydroxymethyl-3,5-di-O-benzoyl-2-fluoro-alpha-D-arabinofuranosyl bromide (13) are presented. Proof of the structure and configuration at all chiral centers of the sugars and the nucleosides were obtained by proton NMR. All five target nucleosides were evaluated for cytotoxicity in human tumor cell lines. The 4'-C-hydroxymethyl clofarabine analogue (16beta) showed slight cytotoxicity in CCRF-CEM leukemia cells.
Shortnacy-Fowler
A T
AT
Southern Research Institute, Birmingham, AL 35255-5305, USA.
Tiwari
K N
KN
Montgomery
J A
JA
Secrist
J A
JA
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D001087:Arabinonucleosides