title: (+)-Sorangicin A: evolution of a viable synthetic strategy.
abstract: An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first and second generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a Co(2)(CO)(6)-alkyne complex, the second involving a KHMDS-promoted epoxide ring formation/opening cascade. Additional highlights include effective construction of the dihydro- and tetrahydropyran ring systems, respectively via a stereoselective conjugate addition/α-oxygenation protocol and a thioketalization/hydrostannane reduction sequence. Late-stage achievements entailed two Julia-Kociénski olefinations to unite three advanced fragments with high E-stereoselectivity, followed by a modified Stille protocol to introduce the Z,Z,E trienoate moiety, thereby completing the carbon skeleton. Mukaiyama macrolactonization, followed by carefully orchestrated Lewis and protic acid-promoted deprotections that suppressed isomerization and/or destruction of the sensitive (Z,Z,E)-trienoate linkage completed the first, and to date only, total synthesis of (+)-sorangicin A (1).
authors.affiliation: Department of Chemistry, Laboratory for Research on the Structure of Matter, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Dong
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Fox
authors.forename: Jehrod B
authors.initials: JB
authors.lastname: Brenneman
authors.forename: John A
authors.initials: JA
authors.lastname: Vanecko
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maegawa