Synthesis and biological activities of 5′-ethylenic and acetylenic modified <ce:small-caps xmlns:ce="http://www.elsevier.com/xml/common/dtd">l-nucleosides and isonucleosides

Two series of 6′-halovinyl-adenosine stereoisomers including 5′-ethylenic and acetylenic substituted l-adenosine, 5′-ethylenic and acetylenic substituted isonucleosides were synthesized. In the l-nucleoside series, compounds <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/6b" xmlns:xlink="http://www.w3.org/1999/xlink">6b</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/8b" xmlns:xlink="http://www.w3.org/1999/xlink">8b</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/10b" xmlns:xlink="http://www.w3.org/1999/xlink">10b</ce:inter-ref> and <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/13b" xmlns:xlink="http://www.w3.org/1999/xlink">13b</ce:inter-ref> showed modest inhibition of SAH hydrolase (21, 44, 50 and 26% respectively) at 100μM. The l-isomers of 5′-ethylenic and acetylenic modified isonucleoside <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/23" xmlns:xlink="http://www.w3.org/1999/xlink">23</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/24" xmlns:xlink="http://www.w3.org/1999/xlink">24</ce:inter-ref> exhibited no activity for the inhibition of SAH hydrolase, however, the d-isomers <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/30" xmlns:xlink="http://www.w3.org/1999/xlink">30</ce:inter-ref> and <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/31" xmlns:xlink="http://www.w3.org/1999/xlink">31</ce:inter-ref> showed some activities in the same test (35 and 21%). It indicated clearly the strict stereochemical requirement for the substrate of SAH hydrolase. Compounds <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/6b" xmlns:xlink="http://www.w3.org/1999/xlink">6b</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/8b" xmlns:xlink="http://www.w3.org/1999/xlink">8b</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/8c" xmlns:xlink="http://www.w3.org/1999/xlink">8c</ce:inter-ref>, <ce:inter-ref xlink:href="sid:S0040-4020(04)01049-X/11b" xmlns:xlink="http://www.w3.org/1999/xlink">11b</ce:inter-ref> exhibited modest to good inhibition effects on the growth of HeLa cells or Bel-7420 cells at 1μM (64, 44, 53 and 82% respectively). [Copyright &y& Elsevier]