Nucleic acid related compounds. 76. Synthesis of 5'(E and Z)-chloro-4',5'-didehydro-5'-deoxyadenosines via chlorination and thermolysis of adenosine 5'-sulfoxides. Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase

Abstract

Treatment of 2',3'-di-O-acetyl-5'-S-(4-methoxyphenyl)-5'-thioadenosine (1a), or its sulfoxides 2a (S r ) and 3a(S s ), with iodobenzene dichloride and potassium carbonate in acetonitrile resulted in formation of the 5'-chloro(and 5',5'-dichloro)-5'-deoxy-5'-[(4-methoxyphenyl)sulfinyl]adenosines 4a, 5a, 6a, and minor diastereomers. Deprotection of 5a gave 5'(S)-chloro-5'-deoxy-5'-[(4-methoxyphenyl)-sulfinyl]adenosine [5b(5'S,S s ] whose stereochemistry and conformation were established by X-ray crystallography. The α-chlorination of sulfoxydes 2a(S r ) and 3a(S s ) occured with predominant retention of configuration at sulffur. Thermolysis of the α-chloro sulfoxides and deprotection gave the chloromethylene derivatives