Total synthesis and study of 6-deoxyerythronolide B by late-stage Cĝ€H oxidation

Erik M. Stang, M. Christina White

Research output: Contribution to journalArticlepeer-review

Abstract

Among the frontier challenges in chemistry in the twenty-first century are the interconnected goals of increasing synthetic efficiency and diversity in the construction of complex molecules. Oxidation reactions of Cĝ€H bonds, particularly when applied at late stages of complex molecule syntheses, hold special promise for achieving both these goals. Here we report a late-stage Cĝ€H oxidation strategy in the total synthesis of 6-deoxyerythronolide B (6-dEB), the aglycone precursor to the erythromycin antibiotics. An advanced intermediate is cyclized to give the 14-membered macrocyclic core of 6-dEB using a late-stage (step 19 of 22) Cĝ€H oxidative macrolactonization reaction that proceeds with high regio-, chemo- and diastereoselectivity (40:1). A chelate-controlled model for macrolactonization predicted the stereochemical outcome of Cĝ€O bond formation and guided the discovery of conditions for synthesizing the first diastereomeric 13-epi-6-dEB precursor. Overall, this Cĝ€H oxidation strategy affords a highly efficient and stereochemically versatile synthesis of the erythromycin core.

Original languageEnglish (US)
Pages (from-to)547-551
Number of pages5
JournalNature Chemistry
Volume1
Issue number7
DOIs
StatePublished - Oct 2009

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Fingerprint

Dive into the research topics of 'Total synthesis and study of 6-deoxyerythronolide B by late-stage Cĝ€H oxidation'. Together they form a unique fingerprint.

Cite this