Synthesis of Novel 7α-Thiol-Bridged Progesterone Derivatives

Abstract

Novel synthetic routes to the formation of progesterone derivatives are of interest due to their potential role in the treatment of breast cancer. This multi-step synthesis proceeds via the dehydrogenation of the endocyclic ketone moiety of the steroid, affording the resulting α,β–γ,δ-unsaturated system. This is followed by 1,6-conjugate addition of p-aminothiophenol, affording the C7 thiol-bridged progesterone analog. The resulting compound was then subjected to a selection of isocyanates affording a variety of novel progesterone derivatives for their medicinal evaluation.

Keywords:

• Steroids
• Progesterone
• Breast cancer
• Enantioselective synthesis

Acknowledgment

The authors wish to thank Dr. R. Clarke and R. Najarian of the Georgetown University School of Medicine for invaluable medicinal discussions.