Stereoselective Synthesis of (+)-SCH 351448: A Unique Ligand System for Sodium, Calcium, and Other Cations

(+)-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 β-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.