title: Efficient formal synthesis of (+/-)-hyphodermin B.
abstract: 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.
authors.affiliation: Natural Product Discovery, Griffith University, Brisbane, QLD, 4111, Australia, and School of Science and Eskitis Institute, Griffith University, Brisbane, QLD, 4111, Australia.
authors.forename: Luke C
authors.initials: LC
authors.lastname: Henderson
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Loughlin
authors.forename: Ian D
authors.initials: ID
authors.lastname: Jenkins
authors.forename: Peter C
authors.initials: PC
authors.lastname: Healy
authors.forename: Marc R
authors.initials: MR
authors.lastname: Campitelli
mesh_terms: D018360:Crystallography, X-Ray; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D020072:Polyporales / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D005663:Furans; D007659:Ketones; D009281:Naphthalenes; C516361:hyphodermin B