Total synthesis of macroviracin D (BA-2836-4).
The first total synthesis of the complex glycolipid macroviracin D (BA-2836-4) (1) is described. This antivirally active metabolite isolated from the mycelium extracts of Streptomyces sp. BA-2836 incorporates a unique 46-membered macrodilactone motif decorated with glycosylated fatty acid appendices. Compound 1 consists of three identical subunits which are closely related to one of the segments found in cycloviracin B(1) (2), another antiviral glycoconjugate previously synthesized in our laboratory. Key steps of the synthesis route to 1 involve the stereoselective, ligand-controlled addition of the functionalized diorganozinc derivative 9 to aldehydes 8 a, b, a series of beta-selective glycosidation reactions using appropriately protected trichloroacetimidate donors, and three esterifications via the Yamaguchi method; one of them is performed intramolecularly to forge the macrocyclic lactone ring of the target in 89 % isolated yield. This total synthesis also firmly establishes the absolute configuration of the subunits of compound 1 as 3R,17S,23R.
Mlynarski
Jacek
J
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany.
Ruiz-Caro
Juliana
J
Fürstner
Alois
A
D000998:Antiviral Agents / Q000138:chemical synthesis*; D002240:Carbohydrate Sequence; D018942:Macrolides / Q000138:chemical synthesis*; D008969:Molecular Sequence Data; D025282:Mycelium / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013302:Streptomyces / Q000737:chemistry
D000998:Antiviral Agents; D018942:Macrolides; D009844:Oligosaccharides; C492878:macroviracin D