A facile, alternative synthesis of 4'-thioarabinonucleosides and their biological activities.
4'-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from D-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hydroxyl groups to give 1-O-acetyl-4-thioarabinose (11), which was condensed with nucleobases to give 4'-thioarabinonucleosides. The 5-substituted-4'-thioaraU (6a-e) derivatives showed anti-HSV-1 activity (ED50 = 0.43-3.50 micrograms/mL). 4'-ThioaraG (6h) and 2,6-diaminopurine 4'-thioarabinonucleoside (4'-thioaraDAP, 6g) showed antiviral activity against several herpes viruses and were particularly potent against human cytomegalovirus (0.010 and 0.022 microgram/mL, respectively).
Yoshimura
Y
Y
Research and Development Division, Yamasa Corporation, Chiba, Japan. yuichi96@choshinet.or.jp
Watanabe
M
M
Satoh
H
H
Ashida
N
N
Ijichi
K
K
Sakata
S
S
Machida
H
H
Matsuda
A
A
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003561:Cytarabine / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects*; D006564:Herpesviridae / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D015459:Leukemia-Lymphoma, Adult T-Cell; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D001087:Arabinonucleosides; D007202:Indicators and Reagents; D013872:Thionucleosides; D003561:Cytarabine