Steroid analogues. Part 4. Synthesis of Δ9-6,7-dinor-5,8-seco-steroids viaβ-lactones

Abstract

The condensation of cycloalkanones with cycloalkanecarboxylic acids has been shown to be a general method for the preparation of cycloalkylidenecycloalkanes bearing different functional groups in the two halves of the molecule.

Condensation of bicyclic hydroxy-ketones representing rings C and D of the steroid nucleus with the dilithium salts of 4-substituted cyclohexanecarboxylic acids (representing ring A) gave β-hydroxy-acids, which were trans-formed by lactonisation and subsequent pyrolysis into 3-substituted Δ⁹-6,7-dinor-5,8-seco-estrenes and -pregnenes. The stereochemistry of these compounds has been elucidated by n.m.r. spectroscopy using a lanthanoid shift reagent, and by reference to conformation theory and the Woodward–Hoffmann rules.

In order to provide model routes to 11-hydroxy-analogues of these compounds, 2-hydroxy-1,1′-bi(cyclohexylidene)(46) was prepared from 1-(cyclohex-1-enyl)cyclohexanecarbonitrile (38) by epoxidation and reduction with lithium–ammonia, and from 1-(cyclohex-1-enyl)cyclohexanecarboxylic acid (40) by epoxidation, chromatography over silica gel, and pyrolysis of the resulting γ-hydroxy-β-lactone. Similar treatment of βγ-unsaturated acids derived from the seco-steroidal β-hydroxy-acids mentioned above gave none of the desired 3-substituted 11α-hydroxy-Δ⁹-6,7-dinor-5,8-seco-steroids.