A domino approach to the enantioselective total syntheses of blennolide C and gonytolide C

Chemistry. 2014 Jul 7;20(28):8628-35. doi: 10.1002/chem.201402495. Epub 2014 Jun 6.

Abstract

The first enantioselective total syntheses of the tetrahydroxanthenone (-)-blennolide C (ent-4) and related γ-lactonyl chromanone (-)-gonytolide C (ent-3) are reported. Key to the syntheses is an enantioselective domino-Wacker/carbonylation/methoxylation reaction to set up the stereocentre at C-4a. Various chiral BOXAX ligands were investigated, including novel (S,S)-iBu-BOXAX, and allowed access to chromane 8 in an excellent enantioselectivity of 99 %. The second stereocentre at C-4 was established employing a diastereoselective Sharpless dihydroxylation. An extensive survey of (DHQ)- and (DHQD)-based ligands enabled the preparation of both the anti-isomer 14 a and the syn-isomer 14 b in very good to reasonable selectivities of 13.7:1 and 1:3.7, respectively. While 14 a was further converted to ent-3 and ent-4, 14 b was elaborated to syn-acid 25 and 2'-epi-gonytolide C 28.

Keywords: dihydroxylation; domino reactions; natural products; tetrahydroxanthones; total synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products
  • Catalysis
  • Chromones / chemical synthesis*
  • Chromones / chemistry
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism
  • Xanthones / chemical synthesis*
  • Xanthones / chemistry

Substances

  • Biological Products
  • Chromones
  • Xanthones
  • blennolide C