UBC Theses and Dissertations

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UBC Theses and Dissertations

Studies directed toward a synthesis of the sesquiterpene zizanoic acid Skinner, Frank W. B.


[Chemical Diagram] The most interesting structural feature of the tricyclic sesquiterpene zizanoic acid is the bicycio[3,2,1]octane system. With the view of synthesizing a bicycio[3,2,1]octane system capable of elaboration to zizanoic acid, the cyclization of compound 220 to compound 131 was investigated. [Chemical Diagram] o-Methoxybenzaldehyde was condensed with diethyl succinate to give ethyl hydrogen cis-γ-o-methoxyphenylitaconate. After hydrogenation, the ethyl hydrogen δ-methoxybenzyl-succinate was cyclized with aluminum chloride to give5-methoxy-l-tetralone-3-carboxylic acid ethyl ester. This was dimethylated to yield 2,2-dimethyl-5-methoxy-l-tetralone-3-carboxylic acid ethyl ester. Hydrolysis of the ester and extension of the carboxylic acid side chain by use of the Arndt-Eistert reaction gave 2,2-dimethy1-5-methoxy-l-tetralone-3-acetic acid methyl ester. The methoxy group was removed with pyridine hydrogen chloride, and the resulting phenol acetylated to give 2,2-dimethyl-5-acetoxy-l-tetralone-3-acetic acid. The carboxylic acid was then reduced with diborane to give 2,2-dimethyl-3-ethyl(2-hydroxy)-5-acetoxy-l-tetralone. The alcohol was converted to the mesylate and the acetate removed to give compound 220 where X=OMs. All attempts to cyclize this compound failed. Attempted cyclization of the reduced species 2,2-dimethyl-3-ethyl(2-methanesulphonate ester)-1,2,3,4-tetra-hydronaphthalene-l,5-diol also failed. 2,2-Dimethyl-3-ethyl(2-bromo-l-oxo)-5-hydroxy-l-tetralone was prepared, but this too failed to react. The bromide 220 where x = Br on treatment with sodium methoxide followed by solid state thermolysis was observed to undergo the desired transformation in up to 20% yield, depending on the solid support used. More promising results were observed in the cyclization of the model compound 7-ethyl(2-methanesulphonate ester)-5,6,7,8-tetrahydro-l-naphthol to the tricyclic compound 1,2,3,4-tetrahydro-3,4a-ethanonaphthalen-5(4aH)-one.

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