title: Total Synthesis of Leupyrrin B1: A Potent Inhibitor of Human Leukocyte Elastase.
abstract: The total synthesis of leupyrrin B1 was accomplished by an expedient strategy that involves an optimized HATU-mediated amide coupling protocol of elaborate substrates. The generally useful procedure was also successfully applied in an improved total synthesis of leupyrrin A1. Finally, leupyrrins A1 and B1 were evaluated toward a panel of proteases, and human leukocyte elastase was discovered as a molecular target of the leupyrrins.
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thiede
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Wosniok
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herkommer
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Anna-Christina
authors.initials: AC
authors.lastname: Schulz-Fincke
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gütschow
authors.affiliation: Kekulé-Institut für Organische Chemie und Biochemie and ‡Pharmazeutisches Institut, Universität Bonn , D-53121 Bonn, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Menche
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; C000607912:leupyrrin B1; D019272:Leukocyte Elastase; D015107:4-Butyrolactone