title: Total synthesis of palau'amine.
abstract: Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N-N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation) and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The synthetic palau'amine is confirmed to exhibit excellent immunosuppressive activity. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.
authors.affiliation: Department of Pharmaceutical Science, Tokushima University, 1-78 Shomachi, Tokushima 770-8505, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Namba
authors.affiliation: Department of Pharmaceutical Science, Tokushima University, 1-78 Shomachi, Tokushima 770-8505, Japan.|Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kaihara
authors.affiliation: Graduate School of Medical and Dental Sciences, Niigata University, Chuo-ku, Niigata 951-8514, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Oda
authors.affiliation: Catalysis Research Center, Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakayama
authors.affiliation: Department of Pharmaceutical Science, Tokushima University, 1-78 Shomachi, Tokushima 770-8505, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakayama
authors.affiliation: Department of Pharmaceutical Science, Tokushima University, 1-78 Shomachi, Tokushima 770-8505, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanino
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009795:Octanes / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D001643:Bridged Bicyclo Compounds; D006146:Guanidines; D007097:Imines; D009795:Octanes; D011758:Pyrroles; D013141:Spiro Compounds; C438976:palau'amine; C026728:octane