title: Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions.
abstract: The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Newton
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Drew
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lawrence
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Willis
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Paddon-Row
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sherburn
mesh_terms: D002384:Catalysis; D002396:Catechols / Q000737:chemistry; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006838:Hydrocarbons / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D002396:Catechols; D004224:Diterpenes; D006027:Glycosides; D006838:Hydrocarbons; C049922:pseudopterosins; C034221:catechol