Azeotropic reflux chromatography: an efficient solution to a difficult separation in the scale-up synthesis of spongistatin 1

Azeotropic reflux chromatography (in which the eluent is continuously recycled by means of refluxing) was used to separate a mixture of spiroketal intermediates in the scale-up synthesis of spongistatin 1, leading to an improved separation and an approximately 35-fold reduction in the amount of solvent used.