Purification of pneumocandins by preparative silica-gel high-performance liquid chromatography

Pneumocandin B-0, a secondary metabolite produced by the fermentation of Glarea lozoyensis gen. et sp. nov., has been found to be a potent antifungal compound. Separation from its major impurity, the isomer pneumocandin C-0, proved to be intractable by reversed-phase chromatography or crystallization and could only be performed by normal-phase liquid chromatography. The scale up of the chromatography from an analytical scare column to a similar to 6 1 bed was conducted to produce large quantities of high purity pneumocandin B-0. The challenges of relatively low productivity due to long elution times and to poor product solubility in the mobile phase were addressed. We speculated that the loading per injection was ultimately limited by nonideal retention mechanisms which led to significant peak broadening at very high loading. (C) 1999 Elsevier Science B.V. All rights reserved.