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

Treatment of 5/-S-(alkyl and aryl)-5'-thioadenosine derivatives 2 with XeF2, or the corresponding sulfoxides 3 with DAST/SbCl3, gave diastereomeric 5'-fluoro compounds which were deprotected to give the 5'-S-(alkyl and aryl)-5'-fluoro-5'-thioadenosine analogues 5. Stereochemistry was established by X-ray crystallography, and F-19 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'-alpha-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.