Catalytic enantioselective diversity-oriented synthesis of a small library of polyhydroxylated pyrans inspired from thiomarinol antibiotics

Mol Divers. 2014 Nov;18(4):701-19. doi: 10.1007/s11030-014-9542-6. Epub 2014 Aug 24.

Abstract

A small library of 30 thiomarinol analogues was successfully synthesised using as a key step-a catalytic enantioselective tandem oxa[4+2] cycloaddition/aldehyde allylboration methodology. With this method, highly substituted α-hydroxyalkyl dihydropyrans were assembled in a single three-component reaction utilizing three different enol ethers and a wide variety of aldehydes, such as aromatic, heteroaromatic, unsaturated and aliphatic aldehydes. In a second operation, a mild and direct method for reducing an acetal unit in the α-hydroxyalkyl dihydropyrans was optimised without the need for protecting a nearby hydroxyl group. This procedure facilitated the synthetic sequence, which was completed by a dihydroxylation of the residual olefin of α-hydroxyalkyl 2H-pyrans to provide the desired library of dihydroxylated pyran analogues reminiscent of the thiomarinol antibiotics. The relative stereochemistry of the resulting library compounds was demonstrated by X-ray crystallography on one of the analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Catalysis
  • Chemistry Techniques, Synthetic
  • Molecular Structure
  • Mupirocin / analogs & derivatives*
  • Mupirocin / chemical synthesis
  • Mupirocin / chemistry
  • Pyrans / chemical synthesis
  • Pyrans / chemistry*
  • Small Molecule Libraries

Substances

  • Anti-Bacterial Agents
  • Pyrans
  • Small Molecule Libraries
  • thiomarinol
  • Mupirocin