Synthesis and antiviral activities of 1'-carbon-substituted 4'-thiothymidines

Bioorganic & Medicinal Chemistry
Kazuhiro HaraguchiMasanori Baba

Abstract

4-Thiofuranoid glycals substituted at the 1-position with methyl (5), (t-butyldimethylsilyloxy)methyl (7), and acetoxymethyl (8) groups were prepared from the 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) (TIPDS)-4-thiofuranoid glycal (3) by way of LDA-lithiation. N-Iodosuccimide-initiated electrophilic glycosidation between silylated thymine and these 1-carbon-substituted 4-thioglycals gave the respective beta-anomers (9, 10, and 13) stereoselectively. Tin radical-mediated removal of the 2'-iodine atom from these products provided the corresponding 1'-branched 4'-thiothymidine derivatives (11, 12, and 14) in good yields. The 1'-hydroxymethyl derivative (15) served as a precursor for the preparation of the formyl (16), cyanoethenyl (17), and cyano (19) derivatives. Among the deprotected 1'-branched 4'-thiothymidines (20-25), the 1'-methyl analogue 20 showed the most potent anti-HSV-1 activity, but it was much less active than the parent compound 4'-thiothymidine.

References

Aug 1, 1991·Journal of Medicinal Chemistry·J A SecristJ A Montgomery
Sep 1, 1991·Journal of Medicinal Chemistry·M R DysonR T Walker
Aug 1, 1988·Journal of Virological Methods·R PauwelsE De Clercq
Jul 3, 2003·Nucleic Acids Research. Supplement·K HaraguchiH Tanaka

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Citations

Oct 16, 2013·Antimicrobial Agents and Chemotherapy·Sophie DuraffourRobert Snoeck
Nov 11, 2006·IDrugs : the Investigational Drugs Journal·Letitia Perry, Andrew Balfe
Mar 18, 2010·Chemical Reviews·Giovanni RomeoPedro Merino
Dec 22, 2006·Journal of Medicinal Chemistry·Hiroki KumamotoYung-Chi Cheng

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