title: A unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins.
abstract: Ellagitannins are a family of polyphenols containing more than 1,000 natural products. Nearly 40% of these compounds contain a highly oxygenated diaryl ether that is one of the most critical elements to their structural diversity. Here, we report a unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins. The strategy involves oxa-Michael addition of phenols to an orthoquinone building block, with subsequent elimination and reductive aromatization. The design of the building block--a halogenated orthoquinone monoketal of gallal--reduces the usual instability of orthoquinone and controls addition/elimination. Reductive aromatization is achieved with perfect chemoselectivity in the presence of other reducible functional groups. This strategy enables the synthesis of different diaryl ethers. The first total synthesis of a natural ellagitannin bearing a diaryl ethers is performed to demonstrate that the strategy increases the number of synthetically available ellagitannins.
authors.affiliation: School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hirokane
authors.affiliation: School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nishii
authors.affiliation: School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamada
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D004987:Ethers / Q000138:chemical synthesis* / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry; D047348:Hydrolyzable Tannins / Q000737:chemistry*; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*
chemical_list: D004987:Ethers; D006841:Hydrocarbons, Aromatic; D047348:Hydrolyzable Tannins; D010100:Oxygen