Asymmetric synthesis of the aminocyclitol pactamycin, a universal translocation inhibitor.

ABSTRACT: An asymmetric total synthesis of the aminocyclopentitol pactamycin is described. The title compound is delivered in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to nonstrategic downstream manipulations. This synthes

SUBMITTER: Sharpe RJ 

PROVIDER: S-EPMC3896956 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature