Efficient Formal Synthesis of (±)-Hyphodermin B

An efficient formal synthesis of hyphodermin B 1, a metabolite of Hyphoderma radula, has been completed
in 15% overall yield. The tricyclic carbon skeleton 3 was rapidly assembled from a novel vinyl enone
via a Diels−Alder reaction, followed by dehydrogenation and anhydride formation. Selective reduction
of anhydride 3 with LiAlH(t-BuO)3 gave hyphodermin B 1 in 99% yield. The structure of hyphodermin
B 1 was confirmed by X-ray crystallographic analysis. The anhydride 3, bearing a γ-carbonyl group,
displayed unexpected reactivity with the anhydride carbonyl closest to the γ-ketone being the most
electrophilic site. This was confirmed by HF/6-31G* calculations. In the presence of base, 3 underwent
a rearrangement to the novel lactone 16.