Efficient formal synthesis of (+/-)-hyphodermin B.

Luke C Henderson, Wendy A Loughlin, Ian D Jenkins, Peter C Healy, Marc R Campitelli

Natural Product Discovery, Griffith University, Brisbane, QLD, 4111, Australia, and School of Science and Eskitis Institute, Griffith University, Brisbane, QLD, 4111, Australia.

The Journal of organic chemistry 2006 Mar 17

filter terms:

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 gamma-carbonyl group, displayed unexpected reactivity with the anhydride carbonyl closest to the gamma-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.

Citation

Luke C Henderson, Wendy A Loughlin, Ian D Jenkins, Peter C Healy, Marc R Campitelli. Efficient formal synthesis of (+/-)-hyphodermin B. The Journal of organic chemistry. 2006 Mar 17;71(6):2384-8