title: Concise Total Synthesis of (+)-Asperazine, (+)-Pestalazine A, and (+)-iso-Pestalazine A. Structure Revision of (+)-Pestalazine A.
abstract: The concise, enantioselective total syntheses of (+)-asperazine (1), (+)-iso-pestalazine A (2), and (+)-pestalazine A (3) have been achieved by the development of a late-stage C3-C8' Friedel-Crafts union of polycyclic diketopiperazines. Our modular strategy enables the union of complex polycyclic diketopiperazines in virtually their final forms, thus providing rapid and highly convergent assembly at the challenging quaternary stereocenter of these dimeric alkaloids. The significance of this carbon-carbon bond formation can be gauged by the manifold constraints that were efficiently overcome, namely the substantial steric crowding at both reactive sites, the nucleophilic addition of C8' over N1' to the C3 carbocation, and the multitude of reactivity posed by the use of complex diketopiperazine fragments in the coupling event. The success of the indoline π-nucleophile that evolved through our studies is notable given the paucity of competing reaction pathways observed in the presence of the highly reactive C3 carbocation generated. This first total synthesis of (+)-pestalazine A also allowed us to revise the molecular structure for this natural alkaloid.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Loach
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Owen S
authors.initials: OS
authors.lastname: Fenton
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Movassaghi
mesh_terms: D054659:Diketopiperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D054659:Diketopiperazines; D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; C437185:asperazine; C000611660:iso-pestalazine A; C567994:pestalazine A