title: Organoboron-based allylation approach to the total synthesis of the medium-ring dilactone (+)-antimycin A(1b).
abstract: The stereoselective synthesis of (+)-antimycin A1b has been accomplished in 12 linear steps and 18% overall yield from (-)-ethyl lactate. A robust, scalable, and highly diastereoselective montmorillonite K10-promoted allylation reaction between an α-silyloxy aldehyde and a substituted potassium allyltrifluoroborate salt provides a general approach to the core stereochemical triad of the antimycin A family. The requisite (Z)-substituted potassium allyltrifluoroborate salt was synthesized using a syn-selective hydroboration/protodeboration of an alkynylboronate ester, followed by a Matteson homologation reaction. The total synthesis leverages an MNBA (Shiina's reagent)-mediated macrolactonization to generate the 9-membered dilactone ring and a late-stage PyBOP-mediated amide coupling employing an unprotected 3-formamidosalicylic acid fragment, thereby shortening the longest linear sequence and, perhaps most notably, generating the antimycin A C7-C8-C9 stereotriad in a single step using a single chiral pool-derived stereocenter.
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, ON M5S 3H6, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Janetzko
authors.forename: Robert A
authors.initials: RA
authors.lastname: Batey
mesh_terms: D000968:Antimycin A / Q000138:chemical synthesis* / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D012459:Salicylates / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001896:Boron Compounds; D007783:Lactones; D012459:Salicylates; C070963:N-formamidosalicylic acid; D000968:Antimycin A