title: Total synthesis of marine eicosanoid (-)-hybridalactone.
abstract: (-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13-membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In this paper, we report on the total synthesis of (-)-hybridalactone (1). The unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically active γ-butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9%. A key step in the synthesis of (-)-hybridalactone (1) is the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis-cyclopropane-γ-lactone derivative. This reaction provided an efficient and stereoselective access to cis-cyclopropane-γ-lactone 12. Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (-)-hybridalactone.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ota
authors.forename: Naoto
authors.initials: N
authors.lastname: Sugata
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ohshiro
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kawashima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyaoka
mesh_terms: D015107:4-Butyrolactone / Q000737:chemistry; D015777:Eicosanoids / Q000138:chemical synthesis / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D000461:Rhodophyta / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D015777:Eicosanoids; D007783:Lactones; D015107:4-Butyrolactone