UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Studies related to the (±)-aristolone and total synthesis of (±)-seychellene De Waal, William


In the first part of this thesis an 8-step synthesis of (±)-4-demethylaristolone 16 is described. This synthetic sequence was eventually to provide the basis for the total synthesis of (±)-aristolone 11. Alkylation of the known 2-methyl-6-n-butylthiomethylenecyclohexanone 77 with methallyl chloride gave, after removal of the blocking group, ketone 79. Treatment of 79 with p-toluenesulfonic acid in refluxing benzene yielded a mixture of olefinic ketones, 79 and 80. Reaction of 80 with diethylcyanomethylphosphonate yielded a mixture of nitriles, 81 and 82, which upon base hydrolysis afforded in good yield, the β,γ-unsaturated carboxylic acid 83 as the sole product. The latter was converted into the crucial diazoketone 86 via the acid chloride 84. Intramolecular cyclization of 86 in the presence of cupric sulfate gave a mixture of (±)-4-demethylaristolone 16 and (±)-5-epi-4-demethylaristolone 88 in a ratio of 2:1. Employing, in each case, two successive Birch reductions, compounds 16 and 88 were converted into decalones 90 and 111, respectively. An alternate synthesis of compound 90 involved the 1,4-conjugate addition of isopropenylmagnesium bromide to the known octalone 91, followed by catalytic hydrogenation of the addition product 97. The compound obtained from this sequence was identical with 90 prepared from (±)-4-demethylaristolone, thus establishing the stereochemistry of the latter. That the predicted stereochemical outcome of the conjugate addition (to 91) was correct, was shown as follows. Ketalization of 97 yielded compound 104, which was converted into its more stable epimer 107, via keto ketal 106. The olefinic ketal 107 upon catalytic hydrogenation followed by acid catalyzed hydrolysis yielded decalone 108. Since compound 108 was clearly different from decalone 111, prepared from (±)-5-epi-4-demethylaristolone 88, it was established that the Birch reduction of the latter had yielded a product with a cis ring junction. In the second part of this thesis an efficient and very stereoselective 16-step synthesis of (±)-seychellene 13 is described. Conjugate addition of lithium dimethylcuprate to the known α,β-unsaturated ketone 142, followed by trapping of the intermediate enolate anion 150 with acetyl chloride, gave in high yield, the enol acetate 151. Epoxidation of the double bond of 151, and thermal rearrangement of the resulting crude product, gave the keto acetate 154. Reaction of 154 with methylenetriphenylphosphorane yielded the olefinic acetate 156. Successive subjection of 156 to hydrogenation [tris(triphenyl-phosphine)chlororhodium], base hydrolysis and Sarett oxidation afforded ketone 144. Reaction of ketone 144 with methyllithium gave the tertiary alcohol 170 which upon dehydration with thionyl chloride in pyridine afforded the olefin 169. Hydroboration-oxidation of the latter gave alcohol 173 which upon treatment with p-toluenesulfonyl chloride gave the tosylate 174 in high yield. Successive treatment of 174 with p-toluenesulfonic acid in methanol and with chromium trioxide in pyridine afforded the crucial keto tosylate 136. Cyclization of 136 in the presence of methylsulfinyl carbanion yielded (±)nor-seychellanone 117. Treatment of the latter with methyl lithium followed by dehydration of the resulting alcohol with thionyl chloride in pyridine afforded, in high yield, (±)-seychellene 13. The latter gave spectra identical with those obtained from the natural product.

Item Media

Item Citations and Data


For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

Usage Statistics