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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

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

Ruscoe Rebecca E RE Fazakerley Neal J NJ Huang Huanming H Flitsch Sabine S Procter David J DJ

Chemistry (Weinheim an der Bergstrasse, Germany) 20151126 1

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 β-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 n ...[more]

PMID: 26527052

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