Synthesis of (-)-Longithorone A: Using Organic Synthesis to Probe a Proposed Biosynthesis

Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12036-41. doi: 10.1073/pnas.0401952101. Epub 2004 Jun 9.

Abstract

We present a full report of our enantioselective synthesis of (-)-longithorone A (1). The synthesis was designed to test the feasibility of the biosynthetic proposal for 1 put forward by Schmitz involving intermolecular and transannular Diels-Alder reactions of two [12]-paracyclophane quinones. We have found that if the biosynthesis does involve these two Diels-Alder reactions, the intermolecular Diels-Alder reaction likely occurs before the transannular cycloaddition. The intermolecular Diels-Alder precursors, [12]-paracyclophanes 38, 49, 59, and 60, were prepared atropselectively, providing examples of ene-yne metathesis macrocyclization. The 1,3-disubstituted dienes produced from the macrocyclizations represent a previously unreported substitution pattern for intramolecular ene-yne metathesis. Protected benzylic hydroxyl stereocenters were used as removable atropisomer control elements and were installed by using a highly enantioselective vinylzinc addition to electron-rich benzaldehydes 26 and 27.

Publication types

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

MeSH terms

  • Bridged-Ring Compounds / chemical synthesis*
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / metabolism
  • Chemistry, Organic / methods
  • Models, Chemical
  • Molecular Structure
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / metabolism
  • Stereoisomerism

Substances

  • Bridged-Ring Compounds
  • Polycyclic Compounds
  • longithorone A