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UBC Theses and Dissertations

Studies related to the synthesis of eremophilane sesquiterpenes concerning the structure of eremophilene Keziere, Robert John


The naturally occurring sesquiterpene, eremophilene, has recently been formulated as (+)-7β-eremophil-3,11-diene 2. The total synthesis of (±) 2, reported herein, was achieved by the following sequence. Reaction of the hydroxymethylene derivative of 3-isopropenylcyclohexanone 130 with 1-diethyl- amino-3-pentanone methiodide 122 in the presence of base (Robinson annelation reaction) readily afforded, after aldol ring closure, l-methyl-7-isopropenyl-Δ¹’⁹ -octal-2-one 127. Reaction of compound 127 with ethereal lithium dimethylcuprate 135 resulted in the selective conjugate addition of a methyl group to octalone 127, thus affording in good yield the all-cis product (±)-7β-eremophil-ll-en-3-one 128. The relative stereochemistry of the eremophilane derivative 128 was confirmed by chemical correlation with hydroxydihydroeremophilone 30 of known absolute configuration. Reaction of the tosylhydrazone derivative of compound 128 with sodium ethylene glycolate in refluxing ethylene glycol (Bamford-Stevens reaction) afforded (±) 2. Comparison of compound (±) 2 with a sample of authentic eremophilene clearly established that the structural assignment (2) originally proposed for eremophilene was incorrect. Dehydration of the naturally occurring eremoligenol 28 with thionyl chloride and pyridine afforded (+)-eremophil-1(10),11-diene 3 which was shown to be identical with authentic eremophilene. Thus the structure and stereochemistry of eremophilene is correctly represented by formulation 3. The synthesis of eremophil-3,11-diene 2 reported herein establishes a stereoselective synthetic entry into the eremophilane class of sesquiterpenoids.

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