Synthesis and oxidation of tricyclic steroid analogues
The subject of this thesis is the synthesis and oxidation of tricyclic steroid analogues. The synthesis of the tricyclic derivatives, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-ones, is described in chapter 1. The synthetic route involves the initial condensation of readily available acetophenone precursors with furfuraldehyde. Subsequent acidic hydrolysis of the resulting furanyl compounds afforded a diketo acid and/or furan acid depending on the nature and position of the substituent on the aromatic ring. Intramolecular condensation of the diketo acids provides a versatile intermediate in the cyclopentene acetic acid derivatives, the hydrogenation and alkylation of which is discussed in chapter 2. Cyclisation of the acetic acid derivatives with acetic anhydride and subsequent deacetylation provided the tricyclic phenolic compounds. The introduction of angular methyl groups in the cyclopentene acetic acid derivatives is discussed in chapter 2. Reductive methylation of these compounds using lithium in liquid ammonia failed, therefore, hydrogenation, followed by direct alkylation was investigated. Hydrogenation of the esters of the cyclopentene acetic acids gave a mixture of the desired reduced compounds along with the super hydrogenated cyclopentane derivatives. It has been shown that hydrogenation of such systems gives rise to two products, namely the trans cyclopentanone and the cis cyclopentane, the trans cyclopentanone arising through 1,4 addition. Permethylation of these cyclopentanones was achieved using KH, NaH and tBuOK. Chapter 3 deals with the oxidation of the phenols prepared in chapter 1 and the trimethyl compounds prepared in chapter 2. A short review on the oxidation of phenols forms the introduction. The oxidation of the tricyclic compound, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-one, using a variety of different oxidising agents did not lead to quinone formation, however phenolic coupling was observed to give a biphenol. Oxidation of the permethylated compounds prepared in chapter 2 with DDQ gave the expected dehydrogenation products via a quinone methide intermediate.