title: Total synthesis of (±)-phomactin A. Lessons learned from respecting a challenging structural topology.
abstract: Our struggles and ultimate success in achieving a total synthesis of phomactin A are described. Our strategy features an intramolecular oxa-[3 + 3] annulation to construct its unique ABD-tricyclic manifold. Although the synthesis would constitute a distinctly new approach with the 12-membered D-ring of phomactin A being assembled simultaneously with the 1-oxadecalin at an early stage, the ABD-tricycle represents a unique structural topology that would pose a number of unprecedented challenges. One challenge concerned elaborating this tricycle to have oxygenation at the proper carbon atoms. To overcome this, we would utilize a Kornblum-DeLaMare ring-opening of a peroxide bridge as well as a challenging late-stage 1,3-allylic alcohol transposition. Further, the structural intricacies of the ABD-tricycle were uncovered by a conformational analysis that would be critical for the C5a-homologation.
authors.affiliation: Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Grant S
authors.initials: GS
authors.lastname: Buchanan
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Cole
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hsung
mesh_terms: D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D006576:Heterocyclic Compounds, 4 or More Rings; C413206:phomactin A