Part I. Efforts directed towards the total synthesis of shionone. Part II. Conversion of estrone to androst-4-EN-3-ONE: a new method for activating the C-9 and C-10 positions of estrogenic steroids for substitution

Part I: An approach to the total synthesis of the triterpene shionone is described, which proceeds through the tetracyclic ketone i. The shionone side chain has been attached to this key intermediate in 5 steps, affording the olefin 2 in 29% yield. A method for the stereo-specific introduction of the angular methyl group at C-5 of shionone has been developed on a model system. The attempted utilization of this method to convert olefin 2 into shionone is described.

Part II: A method has been developed for activating the C-9 and C-10 positions of estrogenic steroids for substitution. Estrone has been converted to 4β,5β-epoxy-10β-hydroxyestr-3-one; cleavage of this epoxyketone using an Eschenmoser procedure, and subsequent modification of the product afforded 4-seco-9-estren-3,5-dione 3-ethylene acetal. This versatile intermediate, suitable for substitution at the 9 and/or 10 position, was converted to androst-4-ene-3-one by known procedures.