title: Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C-H Borylation.
abstract: Verruculogen and fumitremorgin A are bioactive alkaloids that contain a unique eight-membered endoperoxide. Although related natural products such as fumitremorgins B and C have been previously synthesized, we report the first synthesis of the more complex, endoperoxide-containing members of this family. A concise route to verruculogen and fumitremorgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxytryptophan. An iridium-catalyzed C-H borylation/Chan-Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxytryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Dane
authors.initials: D
authors.lastname: Holte
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Jochen
authors.initials: J
authors.lastname: Zoller
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Umemiya
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Simke
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007495:Iridium / Q000737:chemistry; D015394:Molecular Structure; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C431472:6-methoxytryptophan; D007192:Indenes; D007211:Indoles; C009658:verruculogen; D007495:Iridium; C030374:indole; D014364:Tryptophan; C024743:Fumitremorgin A