Copper-Catalyzed Double Additions and Radical Cyclization Cascades in the Re-Engineering of the Antibacterial Pleuromutilin.

ABSTRACT: A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm(II) -mediated radical cyclization cascades of dialdehydes, prepared using a new, one-pot, copper-catalyzed double organomagnesium addition to ?-chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7?steps) allows non-traditional, de novo synthetic access to analogues of the important antibacterial that can't be prepared from the natural product by semisynthesis.

SUBMITTER: Ruscoe RE 

PROVIDER: S-EPMC4736435 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature