Desymmetrization of Cyclopropenes via the Potassium-Templated Diastereoselective 7- exo- trig Cycloaddition of Tethered Amino Alcohols toward Enantiopure Cyclopropane-Fused Oxazepanones with Antimycobacterial Activity

J Org Chem. 2018 May 18;83(10):5650-5664. doi: 10.1021/acs.joc.8b00640. Epub 2018 May 2.

Abstract

A strain-release-driven, cation-templated intramolecular nucleophilic addition of tethered alkoxides to prochiral cyclopropenes is described. Employment of chiral β- and γ-amino alkoxides allowed for highly diastereoselective assembly of a small series of enantiopure cyclopropane-fused oxazepanones. It was shown that the chiral center at C-4 plays a crucial role in controlling desymmetrization of the cyclopropenyl moiety, instigated by a profound potassium-templated effect. The preliminary biological activities of the new cyclopropane-fused medium heterocycles against Gram-positive bacteria, Gram-negative bacteria, mycobacteria, cancer cells, and fungus were evaluated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemistry
  • Amino Alcohols / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cycloaddition Reaction
  • Cyclopropanes / chemical synthesis
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Fungi / drug effects
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Potassium / chemistry
  • Stereoisomerism

Substances

  • Amino Alcohols
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Cyclopropanes
  • cyclopropene
  • cyclopropane
  • Potassium