title: Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels-Alder Reaction.
abstract: The first total synthesis of (+)-cytosporolide A was achieved by a biomimetic hetero-Diels-Alder reaction of (-)-fuscoatrol A with o-quinone methide generated from (+)-CJ-12,373. The dienophile, highly oxygenated caryophyllene sesquiterpenoid (-)-fuscoatrol A, was synthesized from the synthetic intermediate in our previous total synthesis of (+)-pestalotiopsin A. The o-quinone methide precursor, isochroman carboxylic acid (+)-CJ-12,373, was synthesized through a Kolbe-Schmitt reaction and an oxa-Pictet-Spengler reaction. The hetero-Diels-Alder reaction of these two compounds proceeded with complete chemo-, regio-, and stereoselectivity to produce the complicated pentacyclic ring system of the cytosporolide skeleton. This total synthesis unambiguously demonstrates that natural cytosporolide A has the structure previously suggested.
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takao
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Applied Chemistry, Keio University , Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Kin-Ichi
authors.initials: K
authors.lastname: Tadano
mesh_terms: D032701:Biomimetics; D061565:Cycloaddition Reaction; D012717:Sesquiterpenes / Q000138:chemical synthesis*
chemical_list: D012717:Sesquiterpenes; C569249:cytosporolide A