An efficient synthesis of 3-fluoro-5-thio-xylofuranosyl nucleosides of thymine, uracil, and 5-fluorouracil as potential antitumor or/and antiviral agents.
1,2:5,6-Di-O-isopropylidene-alpha-D-glucofuranose by the sequence of mild oxidation, reduction, fluorination, periodate oxidation, borohydride reduction, and sulfonylation gave 3-deoxy-3-fluoro-1,2-O-isopropylidene-5-O-p-toluenesulfonyl-alpha-D-xylofuranose (5). Tosylate 5 was converted to thioacetate derivative 6, which after acetolysis gave 1,2-di-O-acetyl-5-S-acetyl-3-deoxy-3-fluoro-5-thio-D-xylofuranose (7). Condensation of 7 with silylated thymine, uracil, and 5-fluorouracil afforded nucleosides 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) thymine (8), 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) uracil (9), and 1-(5-S-acetyl-3-deoxy-3-fluoro-5-thio-beta-D-xylofuranosyl) 5-fluorouracil (10). Compounds 8, 9, and 10 are biologically active against rotavirus infection and the growth of tumor cells.
Tsoukala
Evangelia
E
Department of Biochemistry and Biotechnology, Laboratory of Organic Chemistry, University of Thessaly, 41221 Larissa, Greece.
Agelis
George
G
Dolinsek
Jan
J
Botić
Tanja
T
Cencic
Avrelija
A
Komiotis
Dimitri
D
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000737:chemistry; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012401:Rotavirus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013941:Thymine / Q000737:chemistry; D014498:Uracil / Q000737:chemistry; D014994:Xylose / Q000031:analogs & derivatives* / Q000737:chemistry; D015215:Zidovudine / Q000494:pharmacology
C520304:3-fluoro-5-thio-xylofuranose; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D009705:Nucleosides; D015215:Zidovudine; D014498:Uracil; D014994:Xylose; D013941:Thymine; D005472:Fluorouracil