Halocarbocyclization entry into the oxabicyclo[4.3.1]decyl exomethylene-δ-lactone cores of linearifolin and zaluzanin A: exploiting combinatorial catalysis

Org Lett. 2012 Feb 17;14(4):968-71. doi: 10.1021/ol203088g. Epub 2012 Feb 8.


A streamlined entry into the sesquiterpene lactone (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In Situ Enzymatic Screening). Absolute stereochemistry derives from kinetic resolution of 5-benzyloxypentene-1,2-oxide, utilizing a β-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis-fusion) is set via formal halometalation/carbocyclization, mediated by [Rh(O(2)CC(3)F(7))(2)](2)/LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-δ-lactone SQL cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl core of xerophilusin R and zinagrandinolide.

Publication types

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

MeSH terms

  • Bridged Bicyclo Compounds / chemistry*
  • Catalysis
  • Cyclization
  • Lactones / chemistry*
  • Methylation
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Sesquiterpenes / chemistry*
  • Stereoisomerism


  • Bridged Bicyclo Compounds
  • Lactones
  • Sesquiterpenes
  • linearifolin
  • zaluzanin A