Open-Chain Carbocyclic Analogs of Adenosine with Dihalovinyl Unit as Potential Inhibitors of S-Adenosyl-L-homocysteine Hydrolase

Abstract

Vinylogously extended deoxyeritadenine derivatives were synthesized as acyclic/carbocyclic analogues of the 6′-halo(homovinyl)adenosines, which are known to be potent inhibitors of S-adenosyl-L-homocysteine hydrolase. Swern oxidation of 9-[3-(t-butyldimethylsilyloxy)-4-hydroxybutyl]adenine (4) followed by Wittig olefination and desilylation gave access to ethyl 6-(adenin-9-yl)-4-hydroxy-2(E)-hexenoate (7) and 5-(adenin-9-yl)-1,1-dibromo-1-penten-3-ol (9). No inhibition of AdoHcy Hydrolase was observed with 7 and 9.

Key Words:

• S-Adenosyl-L-homocysteine hydrolase
• Carbocyclic nucleosides
• Acyclic nucleosides
• Enzyme inhibition

Acknowledgments

This work was partially supported by an award from the American Heart Association, Florida/Puerto Rico Affiliate and Diazyme Laboratories, San Diego, CA. EL thanks Academy of Agriculture for her sabbatical leave and JL is grateful to AHA for the Undergraduate Research Program Award.