Stereoselective synthesis of sugar-modified enyne analogues of adenosine and uridine. Interaction with S-adenosyl-L-homocysteine hydrolase and antiviral and cytotoxic effects.

Sonogashira coupling of (E)-6'-iodohomovinyl nucleosides 1 with (trimethylsilyl)acetylene gave the conjugated 8'-(trimethylsilyl)enyne derivatives of the adenosine 2a and uridine 2b with expected E-stereochemistry. Desilylation of 2a,b with tetrabutylammonium fluoride followed by treatment with N-iodosuccinimide/AgNO(3) afforded 8'-iodoenynes 4a,b. Analogous coupling of (Z)-6'-iodohomovinyl nucleosides 7a,b produced (Z)-8'-(trimethylsilyl)enynes 8a,b, which were deprotected with aqueous trifluoroacetic acid to give the Z-enynes 9a,b.

Stereocontrolled synthesis of diene and enyne sugar-modified nucleosides and their interaction with S-adenosyl-L-homocysteine hydrolase.

Conjugated diene 5-7 and enyne 8 analogs derived from adenosine and uridine were synthesized employing Pd-catalyzed cross-coupling reactions.