Selective synthesis of a new ascomycin rearrangement product (SDZ ASD732) on a pilot plant scale

The process for a pilot plant synthesis and the purification of a semisynth etic ascomycin derivative (1, SDZ ASD732) showing interesting biological ac tivities is described. Conditions for the key transformation, a base-induce d cascade of rearrangement and epimerization reactions of ascomycin leading to the selective formation of the new ascomycin derivative 1, were develop ed and successfully upscaled. Rapid screening of important reaction paramet ers was achieved by using automated parallel synthesis. In addition, a high ly efficient purification process was found and implemented in the pilot pl ant process, resulting in an efficient separation of the semisynthetic asco mycin derivative from its by-products. The purification protocol consisted of preparative silica gel chromatography followed by a crystallisation step . Starting from crystalline ascomycin with a purity of greater than or equa l to 95%, an overall yield of 53% was achieved with a final purity of >98%.