title: Enantiospecific total synthesis of the hapalindoles, fischerindoles, and welwitindolinones via a redox economic approach.
abstract: Full details are provided for the total synthesis of several members of the hapalindole family of natural products, including hapalindole Q, 12-epi-hapalindole D, 12-epi-fischerindole U, 12-epi-fischerindole G, 12-epi-fischerindole I, and welwitindolinone A. Use of the recently developed direct indole coupling enabled an efficient, practical, scalable, and protecting-group-free synthesis of each of these natural products. The original biosynthetic proposal is reviewed, and a revised biosynthetic hypothesis is suggested, validated by the above syntheses. The syntheses are also characterized by an adherence to the concept of "redox economy". Analogous to "atom economy" or "step economy", "redox economy" minimizes the superfluous redox manipulations within a synthesis; rather, the oxidation state of intermediates linearly and steadily increases throughout the course of the synthesis.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Richter
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Masuda
authors.forename: Brandon W
authors.initials: BW
authors.lastname: Whitefield
authors.forename: Tomás
authors.initials: T
authors.lastname: Llamas
authors.forename: Antti
authors.initials: A
authors.lastname: Pohjakallio
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D000470:Alkaloids / Q000096:biosynthesis / Q000138:chemical synthesis*; D040761:Biomimetic Materials / Q000737:chemistry; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis*; D009570:Nitriles / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D026121:Indole Alkaloids; D007211:Indoles; D009570:Nitriles; C491991:fischerindole; C438931:hapalindole Q; C507638:welwitindolinone A