Total syntheses of HMP-Y1, hibarimicinone, and HMP-P1

J Am Chem Soc. 2012 Oct 10;134(40):16765-72. doi: 10.1021/ja307207q. Epub 2012 Sep 26.


Total syntheses of HMP-Y1, atrop-HMP-Y1, hibarimicinone, atrop-hibarimicinone, and HMP-P1 are described using a two-directional synthesis strategy. A novel benzyl fluoride Michael-Claisen reaction sequence was developed to construct the complete carbon skeleton of HMP-Y1 and atrop-HMP-Y1 via a symmetrical, two-directional, double annulation. Through efforts to convert HMP-Y1 derivatives to hibarimicinone and HMP-P1, a biomimetic mono-oxidation to desymmetrize protected HMP-Y1 was realized. A two-directional unsymmetrical double annulation and biomimetic etherification was developed to construct the polycyclic and highly oxidized skeleton of hibarimicinone, atrop-hibarimicinone, and HMP-P1. The use of a racemic biaryl precursor allowed for the synthesis of both hibarimicinone atropisomers and provides the first confirmation of the structure of atrop-hibarimicinone. Additionally, this work documents the first reported full characterization of atrop-hibarimicinone, HMP-Y1, atrop-HMP-Y1, and HMP-P1. Last, a pH-dependent rotational barrier about the C2-C2' bond of hibarimicinone was discovered, which provides valuable information necessary to achieve syntheses of the glycosylated congeners of hibarimicinone.

Publication types

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

MeSH terms

  • Actinobacteria / chemistry*
  • Actinobacteria / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Biomimetics
  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Glycosides / chemical synthesis*
  • Glycosides / chemistry
  • Naphthacenes / chemical synthesis*
  • Naphthacenes / chemistry
  • Oxidation-Reduction
  • Stereoisomerism


  • Antineoplastic Agents
  • Ethers
  • Glycosides
  • Naphthacenes
  • hibarimicinone