Synthesis of a First Estradiol-Adenosine Hybrid Compound

Abstract

An estradiol derivative, bearing an adenosine residue linked at C-16α by a three-carbon side chain, provides access to a new series of substrate-cofactor hybrid compound designed to potentially interact with two binding domains of the enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD). The synthesis of 5′-O-[3-(3′,17′β-dihydroxy-1′,3′,5′(10′)-estratrien-16′α-yl)propanoyl]adenosine (7) is reported focusing on the crucial last steps: the coupling of adenosine residue to estradiol side chain by an ester link and the appropriate final cleavage of three protecting groups.

Keywords:

• 17β-hydroxysteroid dehydrogenase
• Enzyme
• Inhibitor
• Steroid
• Estradiol
• Adenosine

Acknowledgments

We appreciate the financial support of a Collaborative Project Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). We thank the Oncology and Molecular Endocrinology Research Center (CHUQ, Pavillon CHUL) for providing chemical facilities. We also thank Martin Tremblay for helpful suggestions.