Screening large-scale crystallization

Fig. 11.1 Examples of initial crystallization hits from a single on-chip screening experiment of a type II topoisomerase ATPase do-main/ADP, 12mgmL b (A) Irregular spherulite. (B) Phase separation and spherulites with nucleating microcrystals. (C) Thin plate clusters. (D) Thick plate stacks. (E) Well-formed microcrystals. (F) Large single crystals. All scale bars are 100 pm.

In another report by Aelterman et al., the development of a facile and large-scale preparation of the antitumor agent R116010 was demonstrated (Scheme 56.2). In their work, the key strategic improvement was the crystallization-induced diastereomeric dynamic resolution of the aminoketone rac-7, leading to the chiral ketone (S)-7 in 90% yield and 90% enantiomeric purity. After screening 22 chiral acids in numerous solvents, the resolution of aminoketone with ditoluoyltartaric acid in methanol was found to be the optimal process. This new process improves the overall yield from 0.26% to 18.8% without tedious chromatographic separations and hazardous reaction conditions. 

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