Synthesis of novel estrone analogs by incorporation of thiophenols via conjugate addition to an enone side chain

• Key reactions include a diastereoselective OTMS cyanohydrin reaction and aldol.
• Synthesis of C17 estrone analogs possessing alkyl and aryl substituted α,β-unsaturated ketones.
• Synthesis of C24 thioether estrone analogs via a sulfa-Michael addition reaction of p-thiocresolto an enone.

Functionalized estrogen analogs have received interest due to their unique and differing biological activity compared to their parent compounds. The synthesis of a new class of 3-methoxyestrone analogs functionalized at the C17 position possessing both alkyl and aryl substituted α,β-unsaturated ketones is described, along with their thiophenol conjugate addition products.

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