Nucleic Acid Related Compounds. 80. Synthesis of 5'-S-(Alkyl and aryl)-5'-fluoro-5'-thioadenosines with Xenon Difluoride or (Diethylamido)sulfur Trifluoride, Hydrolysis in Aqueous Buffer, and Inhibition of S-Adenosyl-L-homocysteine hydrolase by derived "Adenosine 5'-Aldehyde" Species

Abstract

Treatment of 5'-S-(allyl and aryl)-5'-thioadenosine derivatives 2 with XeF 2 , or the corresponding sulfoxides 3 with DAST/SbCl 3 , gave diastereomeric 5'-fluoro compounds which were deprotected to give the 5'-S-(allyl and aryl)-5'-fluoro-5'-thioadenosine analogues 5. Stereochemistry was established by X-ray crystallography, and 19 F NMR chemical shifts were definitive for configurationally-related 5'-fluoro diastereomers. Sulfoxidation and thermolysis afforded the fluoromethylene analogues with retained relative configuration. The nucleoside 5'-α-fluoro thioethers 5 underwent spontaneous hydrolysis in aqueous buffer to give derived «adenosine 5'-aldehyde» species which caused potent time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase