The formal synthesis of ($-$)-A-23187 (calcimycin), an ionophore antibiotic which is unique in its ability to bind and transport calcium and magnesium and has been shown to uncouple oxidative phosphorylation in rat liver mitochrondria, has been completed. The synthesis of an enantiomerically pure carboxylic acid pyrrole, which has been previously converted to A-23187 and analogs thereof, constitutes a formal synthesis of the antibiotic.

The route to A-23187, which utilizes the 3-methyl-$\gamma$-butyrolactone approach to the synthesis of polypropionates to construct the C$\sb$-C$\sb{20}$ portion of the antibiotic, starts with readily available (S)-3-methyl-$\gamma$-butryolactone and (S)-2-methyl-4(E)-hexen-2-ol and proceeds in about thirty-five steps. The synthesis of the C$\sb$-C$\sb$ fragment utilizes a Johnson ortho ester Claisen rearrangement with (R)-2-methyl-4(E)-hexen-2-ol to establish the stereochemistry of the C$\sb$ methyl group. Acid catalyzed cyclization of a $\beta$-hydroxy ester sets the stereochemistry at the spiroketal center by virtue of the anomeric effect.