Catalytic enantioselective synthesis of (-)-prostaglandin E1 methyl ester based on a tandem 1,4-addition-aldol reaction

J Org Chem. 2002 Oct 18;67(21):7244-54. doi: 10.1021/jo025987x.

Abstract

Catalytic enantioselective 1,4-additions and tandem 1,4-addition-aldol reactions of dialkylzinc reagents to cyclopentene-3,5-dione monoacetals in the presence of an in situ generated Cu(OTf)(2)/chiral phosphoramidite catalyst result in highly functionalized cyclopentane building blocks with ee's up to 97%. A new synthesis of cyclopentene-3,5-dione monoacetals is presented as well as its use in a tandem 1,4-addition-aldol protocol for the catalytic asymmetric total synthesis of (-)-PGE(1) methyl ester. This synthesis represents a new approach to this class of natural products. By using only 3 mol % of an enantiomerically pure catalyst in the key step, the absolute configurations at three stereocenters of the basic structure of the PGE(1) are established at once.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Alprostadil / analogs & derivatives*
  • Alprostadil / chemical synthesis*
  • Alprostadil / chemistry
  • Indicators and Reagents
  • Models, Molecular
  • Molecular Conformation

Substances

  • Indicators and Reagents
  • prostaglandin E1 methyl ester
  • Alprostadil