title: MNBA-mediated β-lactone formation: mechanistic studies and application for the asymmetric total synthesis of tetrahydrolipstatin.
abstract: Various β-lactones were prepared from β-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.
authors.affiliation: Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. shiina@rs.kagu.tus.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Shiina
authors.forename: Yuma
authors.initials: Y
authors.lastname: Umezaki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kuroda
authors.forename: Takashi
authors.initials: T
authors.lastname: Iizumi
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Katoh
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009579:Nitrobenzoates / Q000737:chemistry*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology*
chemical_list: C526944:2-methyl-6-nitrobenzoic anhydride; D000812:Anhydrides; D019440:Anti-Obesity Agents; D003432:Cross-Linking Reagents; D007783:Lactones; D009579:Nitrobenzoates; C054164:lipstatin; D008049:Lipase