The total synthesis of dragmacidins G and H was achieved for the first time by employing nucleophilic aromatic substitution and site-selective cross-coupling reactions using appropriately functionalized pyrazines as substrates. The evaluation of antibacterial activities of dragmacidin G, dragmacidin H, and synthetic analogues against Staphylococcus aureus and the efflux pump-deficient Salmonella Typhimurium revealed that the presence of a Br group on the indole ring adjacent to the sulfide unit was important for increasing antibacterial activities.
Herein, we report the unusual skeletal rearrangement of spiro[4.5]decadienone to benzoxepane. In particular, Lewis acid-promoted epoxide-opening ipso-cyclization of aryl epoxides afforded spiro[4.5]decadienone intermediates. Subsequent thermal activation assembled a benzoxepane core via rearomative molecular reorganization. The sequence was high-yielding and highly diastereoselective but sensitive to the aromatic substitution pattern and the epoxide side chain. Mechanistic studies suggested that the rearrangement proceeded via an uncommon intramolecular enolate attack onto the electrophilic O of p-quinone oxonium zwitterion. DFT calculations helped rationalize the product distribution and the origin of diastereoselectivity. Initial investigation into the application of this chemical transformation is also presented.
Chemical and Pharmaceutical Bulletin 71(8) 624-632 2023年8月1日
To develop dearomatization reactions based on a nucleophilic activation of phenols, naphthols, and indoles, ipso-Friedel–Crafts-type C-alkylation must be selectively promoted over competitive O- or N-alkylation reactions. Resolving this chemoselectivity issue is essential for developing this class dearomatization reaction. We found that various dearomatization reactions could be developed using appropriately designed aromatic substrates with an electrophilic moiety for intramolecular reactions. This review describes the transition-metal-catalyzed dearomatization reactions developed by our group. π-Allylpalladium species, η3-propargylpalladium species, alkynes activated by Au(I) species, and silver carbene species could be applied as electrophiles in our reaction system, which provided access to a wide variety of dearomatized products from planar aromatic compounds in a highly chemoselective manner.
This paper presents the advances in the synthesis of dragmacidin E. Since its isolation from a southern Australian deep-water marine sponge by Capon et al. in 1998, the Funk, Feldman, Jia, and Nemoto groups have conducted synthetic studies on this bis-indole alkaloid. An overview of the synthetic studies reported thus far, including the total synthesis of (±)-dragmacidin E achieved by Feldman et al. in 2011, is presented.