A concise synthesis of the fully functional lactide core of cycloviracin B with implications for the structural assignment of related glycolipids.
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.
Fürstner
Alois
A
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany. fuerstner@mpi-muelheim.mpg.de
Albert
Martin
M
Mlynarski
Jacek
J
Matheu
Maribel
M
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
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D006017:Glycolipids; D018942:Macrolides; C077636:cycloviracin B1