UBC Theses and Dissertations
Carbocycle construction in terpenoid synthesis : subtitle the total synthesis of (±)-sarcodonin G and (±)-1-epi-9-norpresilphiperfolan-9-one Gilbert, Michael W.
Carbocycle construction represents a significant challenge in synthetic studies geared towards terpenoid natural products. A step-wise annulation approach to the construction of the diterpenoid framework of the cyathanes (54) was investigated, ultimately leading to the first reported total synthesis of (±)-sarcodonin G (36). The sesquiterpenoid carbon skeleton of the presilphiperfolanes (270) was assembled via a tandem cyclization strategy, affording the known ketone, (±)-1-epi-9- norpresilphiperfolan-9-one (306). The construction of the cyathane 5-6-7 fused tricyclic framework commenced with 3-methyl-2-cyclohexen-1-one 38, representing the B-ring. The annulation sequences for A and C-rings utilized the bifunctional reagents 39 and 44, respectively. With the help of these reagents, the 5-6-6 fused tricycle 155 was quickly assembled from 38. Intermediate 155 was further elaborated, including a key SmI₂-mediated ring expansion, to afford the 5-6-7 fused tricycle 159, which displays the complete cyathane framework. The target structure, (±)-sarcodonin G (36), was obtained in several steps from 159. In addition, an advanced intermediate in the synthesis of 36 was transformed into substance 269, a likely synthetic precursor of the corresponding keto triol natural product, (±)-cyathin A₄ (37). Assembly of the presilphiperfolane 5-5-6 fused tricyclic carbon skeleton 270 was approached via a tandem cyclization strategy involving free-radical reactions. The key intermediates of this synthetic study, xanthates 367, were readily prepared from enone 49 in several steps. Bu₃SnH-mediated free-radical reaction of 367 yielded a mixture of cyclization products, alkenes 368, whose frameworks include the carbon skeleton of the natural product presilphiperfolan-9-ol (53). Alkenes 368 were subjected to oxidative cleavage conditions, affording the known ketone (±)-1-epi-9-norpresilphiperfolan-9-one (306). [diagram]
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