Conformationally constrained analogues of diacylglycerol. 24. Asymmetric synthesis of a chiral (R)-DAG-lactone template as a versatile precursor for highly functionalized DAG-lactones

Org Lett. 2004 Jul 8;6(14):2413-6. doi: 10.1021/ol0492041.

Abstract

[structure: see text] Commercially available 2-methylenepropane-1,3-diol was converted to chiral epoxide (R)-2 via Sharpless asymmetric epoxidation in >96% ee. Regiospecific epoxide ring opening and reduction of the intermediate alkyne set the stage for a one-pot lactonization to give (R)-6, a convenient precursor for all functionalized chiral DAG-lactones used as potent PK-C ligands. The synthesis of the most potent DAG-lactones known to date, (Z)-10 and (E)-10, served to confirm PK-C's exclusive preference for the (R)-stereochemistry in this class of compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalysis
  • Diglycerides / chemistry*
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / chemistry
  • Lactones / chemical synthesis*
  • Ligands
  • Molecular Conformation
  • Molecular Structure
  • Protein Kinase C / metabolism*
  • Stereoisomerism

Substances

  • 1,2-diacylglycerol
  • Diglycerides
  • Epoxy Compounds
  • Lactones
  • Ligands
  • Protein Kinase C