title: Total Synthesis of Leupyrrins A1and B1, Highly Potent Antifungal Agents from the Myxobacterium Sorangium cellulosum.
abstract: Full details on the design, elaboration, and application of efficient strategies for the high-yielding total syntheses of leupyrrins A1and B1, unique antifungal agents from the myxobacterium Sorangium cellulosum, are reported. A sequential zirconocene-mediated diyne-cyclization, and regioselective opening of the zirconacyclopentadiene intermediate enabled a concise entry into the unique dihydrofuran fragment, whereas another domino reaction was developed for the butyrolactone involving a one-pot lactol opening, stereoselective aldehyde addition and in situ lactonization. Furthermore, an innovative sp2-sp3-cross-coupling for pyrrole functionalization and an optimized HATU-mediated amide coupling protocol of two elaborate fragments were established. In addition, an unusual protective group strategy, involving a Teoc-acetonide protected amine in combination with tert-butyl and acetate esters, was successfully elaborated. These tactics and strategies are generally useful and may be also applied in the synthesis of other functionalized compounds. It is expected that the material which was obtained by these total syntheses will enable the further exploration of the biological profile of these potent antifungal agents.
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0003-0352-6094
authors.initials: S
authors.lastname: Thiede
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Wosniok
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.|Current address: GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herkommer
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.|Current address: Dottikon Exclusive Synthesis AG, Dottikon, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Debnar
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.|Current address: Scripps Research Institute, La Jolla, USA.
authors.forename: Maoqun
authors.initials: M
authors.lastname: Tian
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.|Current address: Institute of Quality Standard and Testing Technology for Agro-products, Chinese Academy of Agricultural Sciences, Key Laboratory of Agro-food Safety and Quality, Ministry of Agriculture, Beijing, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schrempp
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie, Universität Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Dirk
authors.identifier: http://orcid.org/0000-0002-4724-8383
authors.initials: D
authors.lastname: Menche
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis*; D003500:Cyclization; D006801:Humans; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D015040:Zirconium / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D009942:Organometallic Compounds; C481579:leupyrrin A1; C000607912:leupyrrin B1; C023398:Zirconocene dichloride; D015040:Zirconium; D015107:4-Butyrolactone
keywords: antifungal agent; domino reactions; leupyrrin; natural products; total synthesis