De Novo Design and Asymmetric Synthesis of a C-1/2 Benzodioxin Fused Glycoside Analogue of Lincomycin

An in silico designed benzodioxin fused analogue of a des-(1-hydroxyethyl)-lincomycin analogue was synthesized in a de novo asymmetric fashion from an achiral acylfuran, a 4-(n-Pr)-N-methyl-proline, and catechol. The synthesis of the 6-amino-galactose portion of the lincomycin analogue necessitated the development of a novel stereospecific tandem Pd-glycosylation/1,4-addition reaction between catechol and an N-Cbz-protected 6-amino-pyranone with a Pd-π-allyl leaving group at the C-1 position. The desired galacto-stereochemistry was installed by a subsequent stereoselective ketone reduction, alcohol elimination, and diastereoselective dihydroxylation of the C-3/4 alkene.