Unified route to the palmarumycin and preussomerin natural products. Enantioselective synthesis of (-)-preussomerin G.
The total syntheses of eight members of the palmarumycin family have been achieved, with identification of the absolute stereochemistry for three of these natural products. In addition, the ras-farnesyl transferase inhibitor (-)-preussomerin G has been synthesized, achieving the first enantioselective route for accessing this family of natural products. Highlights of the synthetic work include an asymmetric epoxidation of a cyclic enone in excellent yield and enantiomeric excess and a potentially biomimetic oxidative spirocyclization for the introduction of the bis-spiroketal array unique to the preussomerin natural products.
Barrett
Anthony G M
AG
Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AY, UK. agmb@ic.ac.uk
Blaney
Frank
F
Campbell
Andrew D
AD
Hamprecht
Dieter
D
Meyer
Thorsten
T
White
Andrew J P
AJ
Witty
David
D
Williams
David J
DJ
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003500:Cyclization; D004146:Dioxanes / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D004852:Epoxy Compounds; D005658:Fungi / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
D001688:Biological Products; D004146:Dioxanes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; D009281:Naphthalenes; D013141:Spiro Compounds; C462860:palmarumycin C12; C462879:palmarumycin C2; C462859:palmarumycin CP2; C410323:preussomerin G; C422643:palmarumycin CP(1)