Stereocontrolled synthesis of the C21-C38 fragment of the unnatural enantiomer of the antibiotic nystatin A1

Chemistry. 2004 Mar 19;10(6):1545-57. doi: 10.1002/chem.200305540.

Abstract

The C(21)-C(38) fragment all-trans-41 of the unnatural enantiomer 1 of nystatin A(1) was prepared starting from the N-propionyl oxazolidinone 9. Aldol adduct ent-8 (ee > 96 %) derived in two steps was hydroborated with (thexyl)BH(2). Oxidative work-up and treatment with acid furnished delta-lactone 4. It contains the complete stereotetrade of the target molecule. The alpha,beta-unsaturated ester 28 was reached after another four steps. It should be a precursor for the polyene moieties of a variety of polyol,polyene macrolides. Illustrating that, the alpha,beta-unsaturated aldehyde 29 obtained from 28 and DIBAL was extended by 10 C atoms in four steps yielding the C(21)-C(38) segment 41. The latter set of transformations included the regio- and stereoselective Claisen rearrangement 32-->35.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Molecular Conformation
  • Nystatin / chemical synthesis*
  • Nystatin / chemistry
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Stereoisomerism

Substances

  • Anti-Bacterial Agents
  • Peptide Fragments
  • Nystatin