title: Total Synthesis of Zaragozic Acid C: Implementation of Photochemical C(sp3)-H Acylation.
abstract: Zaragozic acid C (1) was isolated as a potent squalene synthase inhibitor. The 2,8-dioxabicyclo[3.2.1]octane core of 1 is decorated with the three hydroxycarbonyl (C3,4,5), two hydroxy (C4,7), one acyloxy (C6), and one alkyl (C1) groups. Installation of the contiguous C4- and C5-fully substituted carbons presents a formidable synthetic challenge. Our approach to address this problem used a two-step photochemical C(sp3)-H acylation. Persilylated d-gluconolactone 4 was derivatized into 3 with the 1,2-diketone moiety at the C5-tetrasubstituted center. Norrish-Yang cyclization of 3 under violet LED irradiation followed by oxidative opening of the resultant α-hydroxycyclobutanone regio- and stereoselectively transformed the electron-rich tertiary C(sp3)-H bond at C4 into a C(sp3)-C bond to produce densely functionalized 2. A subsequent series of judicious functional group transformations gave rise to 1.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawamata
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masanori
authors.identifier: 0000-0001-9204-194X
authors.initials: M
authors.lastname: Nagatomo
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masayuki
authors.identifier: 0000-0003-3274-551X
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000215:Acylation; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008968:Molecular Conformation; D055668:Photochemical Processes
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C079090:zaragozic acid C