Highly stereoselective synthesis and biological properties of nucleoside analogues bearing a spiro inserted oxirane ring.
Starting from 2',5'-di-O-TBDMS-3'-ketouridine 1 or its thymine analogue 2, both xylo (3-10) and ribo (20) epimers of a series of 3"-substituted 3'-spironucleosides have been obtained in good yields and with a total stereoselectivity. Most new compounds were moderately cytotoxic with in some cases slightly selective antiproliferative activities. None of these compounds was active against HIV, but some other antiviral activities against HSV-2, CMV, EBV, or VZV, in the micromolar range, were noted in specific cases.
Tronchet
J M
JM
Department of Organic Pharmaceutical Chemistry, University of Geneva, Sciences II, Switzerland.
Kovacs
I
I
Seman
M
M
Dilda
P
P
De Clercq
E
E
Balzarini
J
J
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002470:Cell Survival; D003587:Cytomegalovirus / Q000187:drug effects; D005027:Ethylene Oxide / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D014645:Herpesvirus 3, Human / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured
D009705:Nucleosides; D013141:Spiro Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005027:Ethylene Oxide