Synthetic efforts toward the convergent construction of the tetracyclic triterpenoids cucurbitacins B and D are described. The results of a Diels-Alder study examining the effects of steric and electronic variations of 2-methyl-2-cyclohexenone on the endo/exo-diastereoselectivity of the reaction are presented. The diastereomer of the core of the cucurbitacins, epimeric at C8, C9, and C10, 51, was synthesized via a highly regio- and stereoselective Diels-Alder reaction of the diene 4 and the novel dienophile 50.
While thermolysis of the macrobicyclic triene lactone 12 did not produce the expected bicyclic transannular Diels-Alder (BTADA) product 13, heating the corresponding ether 18 to 110 °C for 4 h afforded a quantitative yield of the desired cycloadduct 19, which could be easily reduced to the perhydrophenanthrene, an ABC ring analogue of fusidic acid 1. Theoretical calculations with hybrid density functional theory (B3LYP/6-31G(d)) help rationalize why the lactone does not cyclize whereas the ether does.
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