title: Towards the synthesis of massadine: a unified strategy for the stereoselective synthesis of the carbocyclic C,D-ring subunit.
abstract: Massadine is a hexacyclic marine natural product, which belongs to the family of pyrrole-imidazole alkaloids. Herein, we describe a unified approach to the C,D-ring subunit of this sponge metabolite based on the exploitation of a norbornene scaffold for the stereocontrolled construction of massadine's carbon skeleton. Highlights of the sequence presented include the application of a stereospecific norbornyl rearrangement for facile introduction of an oxygen at the C7-position within the norbornene nucleus, a highly regioselective and end group differentiating ozonolytic scission of a C-C double bond, and an oxidative decarboxylation reaction for the installation of the hindered secondary C2-alcohol function. Furthermore, the iterative assembly of the two guanidine entities as well as the implementation of the spirocyclic junction between the C- and the D-rings are described. Collectively, these key transformations permit an entry to an appropriately functionalized carbon framework, which will serve as a starting point for our efforts toward the completion of the synthesis of massadine.
authors.affiliation: ETH Zürich HCI H335, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Breder
authors.forename: Gary M
authors.initials: GM
authors.lastname: Chinigo
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Waltman
authors.forename: Erick M
authors.initials: EM
authors.lastname: Carreira
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry*; D010084:Oxidation-Reduction; D011083:Polycyclic Compounds / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D001688:Biological Products; D011083:Polycyclic Compounds; D011758:Pyrroles; C478874:massadine