title: A concise synthesis of the fully functional lactide core of cycloviracin B with implications for the structural assignment of related glycolipids.
abstract: The absolute stereochemistry at the site of attachment of the fatty acid residues to the lactide core of the glycolipids cycloviracin B1 (1) and glucolipsin A (13) has been elucidated as (3R,3'R) by comparison of their 13C NMR data with those of the three possible, differently configured core structures 9, 12, and 14. Moreover, a careful analysis of this set of NMR data allows us to conclude that the structures previously proposed for a seemingly closely related class of antivirally active compounds, i.e., the fattiviracin family, need revision. The key step en route to the symmetrical dilactones 9 and 12 consists of a highly efficient cyclodimerization process which exploits the template effect exerted by potassium cations on the hydroxy acid cyclization precursor. The latter is obtained in excellent overall yield by a sequence involving ring-opening Claisen condensation of pentadecanolide to form the functionalized beta-ketoester 4, asymmetric hydrogenation catalyzed by [(BINAP)RuCl2]2.NEt3, and a beta-selective glycosylation reaction using trichloroacetimidate 6. The unsymmetrical dilactone 14, in contrast, is prepared by a stepwise approach based on a Yamaguchi lactonization as the means to close the macrocyclic ring.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany. fuerstner@mpi-muelheim.mpg.de
authors.forename: Alois
authors.initials: A
authors.lastname: Fürstner
authors.forename: Martin
authors.initials: M
authors.lastname: Albert
authors.forename: Jacek
authors.initials: J
authors.lastname: Mlynarski
authors.forename: Maribel
authors.initials: M
authors.lastname: Matheu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry*; D018942:Macrolides; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D006017:Glycolipids; D018942:Macrolides; C077636:cycloviracin B1