Two sequences leading to the total synthesis of several octahydrochrysene derivatives are described; in particular, the synthesis of B-nor-cis-2-methoxy-8α-acetoxy-5-keto-10a-methyl-5,6,7,8,9,10,10a-octahydrochrysene (XL) is achieved. In one sequence an olefinic bond at the 5,6 position of ring B (XXXII) was introduced by reduction of cis-2-methoxy-8α-acetoxy-5-keto-10a-methyl-5,6,6a, 7,8,9,10,lOa-octahydrochrysene (XIV) with sodium borohydride, followed by dehydration with phosphorus pentoxide.Subsequent reaction at the olefinic linkage by osmium tetroxide provided the α-diol (XXX), which upon treatment with periodic acid yielded a hemiacetal (XXXIV). Cyclization on alumina then provided the B-nor internal aldol condensation product (XXXIX). The latter readily underwent / oxidation with Jones' reagent to result in the B-nor-5-keto acetate (XL). In an alternate sequence the cis-2-methoxy-8α-acetoxy-5-keto-5,6,6a,7,8, 9,10, 10a-octahydrochrysene (XIV) is oximinated at the 6-position with isoamyl nitrite and the oxime is converted by acid hydrolysis to a 5,6-diketo-8-hydroxy compound (XLII). An attempt was made to accomplish a benzilic acid rearrangement on the α-diketo compound and the resulting product (XLVII) was subjected to lead tetra-acetate oxidation in the hope that the B-nor-5-keto system (XLVIII) could be obtained. The structures from the last two reactions were only tentatively established. A critical discussion of the n.m.r. data is reserved to a separate section of the thesis. Tentative assignments of all the aromatic protons were made. Of special note is the chemical shift dependence of the proton at C₄ on the substitution at C₅. Configurational and conformational assignments of the ring A/B system were made on the basis of angular methyl and 8β-proton frequencies. / Science, Faculty of / Chemistry, Department of / Graduate

A sequence leading to the total synthesis of certain derivatives in the 11, 12-seco (see XXIV) and 5, 6-seco hydro-chrysene (see XXXI) series is described. The synthesis employs in its initial stages the Robinson-Mannich base reaction and the Michael condensation reaction to construct the parent tetracyclic skeleton. Condensation of 6-methoxy-2-tetralone with 1-diethylamino-3-pentanone methiodide produced an isomeric mixture of tricyclic ketones. This mixture was then condensed with methyl vinyl ketone to yield a tetracyclic ketol (XII) which in turn was converted to the tetracyclic ketone (XIII) by reaction with sodium methoxide. By appropriate modifications, this latter substance may then be utilized for the synthesis of a variety of hydrochrysene analogues. Oxidation of trans-anti-trans-2-methoxy-8β-acetoxy-10a -methyl-4b, 5, 6, 6a, 7, 8, 9, 10, 10a, 10b, 11, 12-dodecahydrochrysene (XVI) with t-butyl chromate solution gave not only the 12-keto derivative (XIX), but the 5-keto octahydrochrysene analogue (XX) as well as small amounts of the octahydrochrysene (XVII) and the hexahydrochrysene analogue (XVIII). The olefinic bond at the 11, 12 position of ring C (XXII) was introduced by reduction of the 12-keto derivative (XIX) with sodium borohydride, followed by dehydration with phosphorus pentoxide. Subsequent ozonization of XXII yielded the dialde-hyde (XXIV). The olefinic bond at the 5, 6 position of ring B (XVIII) was introduced by the same procedure as in the ring C series. This hexahydrochrysene analogue (XVIII) was reacted with osmium tetroxide to provide the diol (XXVI), which upon treatment with periodic acid yielded the aldol condensation product directly without isolation of the dialdehyde. Nuclear magnetic resonance (n. m. r.) spectroscopy was found to be a powerful tool for the purpose of the characterization of these rather complex molecules. / Science, Faculty of / Chemistry, Department of / Graduate