Studies toward the syntheses of pluramycin natural products. The first total synthesis of isokidamycin

Abstract

We report the first total synthesis of the complex C-aryl glycoside isokidamycin, the epimer of the naturally-occurring pluramycin antibiotic kidamycin. The synthesis features a highly efficient Diels–Alder reaction between a substituted naphthyne and a glycosylated furan to form the anthracene core bearing a pendent angolosamine C-glycoside. The regiochemical outcome of the Diels–Alder reaction was controlled by employing a disposable silicon tether to link the reactive naphthyne and the glycosyl furan, rendering the cycloaddition intramolecular. The benzopyranone moiety of the aromatic nucleus was appended by cyclization of a functionalized vinylogous amide onto an advanced anthrol intermediate. The vancosamine amino glycoside was introduced by an O→ C-glycoside rearrangement that produced the β-anomer. Subsequent refunctionalizations then led to isokidamycin.