title: A Bioinspired Synthesis of (±)-Rubrobramide, (±)-Flavipucine, and (±)-Isoflavipucine.
abstract: A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α-bromo-β-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β-epoxy-γ-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (±)-Flavipucine and (±)-isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α-bromo-β-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)-flavipucine, which was converted into (±)-isoflavipucine by thermal isomerization.
authors.affiliation: Graduate School for Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto, 606-8522, Japan.
authors.forename: Shoma
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Graduate School for Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto, 606-8522, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Komori
authors.affiliation: Faculty of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Kita, 21 Nishi 11, Sapporo, 001-0021, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Faculty of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Kita, 21 Nishi 11, Sapporo, 001-0021, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Monde
authors.affiliation: Graduate School for Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto, 606-8522, Japan. kuramoch@kpu.ac.jp, kuramoch@rs.tus.ac.jp.|Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. kuramoch@kpu.ac.jp, kuramoch@rs.tus.ac.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kuramochi
authors.affiliation: Graduate School for Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Shimogamo Hangi-cho, Sakyo-ku, Kyoto, 606-8522, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsubaki
keywords: biomimetic synthesis; configuration determination; lactams; total synthesis; vibrational spectroscopy