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 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.
Henderson
Luke C
LC
Natural Product Discovery, Griffith University, Brisbane, QLD, 4111, Australia, and School of Science and Eskitis Institute, Griffith University, Brisbane, QLD, 4111, Australia.
Loughlin
Wendy A
WA
Jenkins
Ian D
ID
Healy
Peter C
PC
Campitelli
Marc R
MR
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
D005663:Furans; D007659:Ketones; D009281:Naphthalenes; C516361:hyphodermin B