Stereoselective synthesis of (+)-SCH 351448: a unique ligand system for sodium, calcium, and other cations

J Org Chem. 2005 Aug 5;70(16):6321-9. doi: 10.1021/jo0507993.

Abstract

(+)-SCH 351448 (Na+ salt A) was synthesized employing ring-closing olefin metathesis reaction of an open diene diester intermediate for construction of the 28-membered macrodiolide structure. The open diene diester was prepared from the monomeric hydroxy carboxylic acid and two different olefin fragments. The monomeric hydroxy acid was synthesized via Julia-Julia coupling reaction of intermediates derived from the same olefinic fragments. Oxane units in these fragments were prepared by radical cyclization reactions of beta-alkoxyacrylates. Analogous SCH 351448 salts incorporating other mono- and divalent cations may be prepared. Under acidic conditions, SCH 351448 (Na+ salt A) was the most stable complex, but SCH 351448 (Ca2+ salt) and (Na+ salt B) appear to be physiologically important species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / chemistry*
  • Cations / chemistry
  • Crystallography, X-Ray
  • Lactones / chemical synthesis*
  • Lactones / chemistry*
  • Ligands
  • Molecular Structure
  • Sodium / chemistry*
  • Solvents
  • Stereoisomerism

Substances

  • Cations
  • Lactones
  • Ligands
  • SCH 351448
  • Solvents
  • Sodium
  • Calcium