Serendipitous discovery of a pH-dependant atropisomer bond rotation: Toward a write-protectable chiral molecular switch?☆

Factors influencing the interconversion of a new class of dibenzodiazepine sulfonamide atropisomers

“…11 In the present case, we found no effect of additives (triethylamine and acetic acid) or aqueous buffer of different pH (3, 7, and 10) on the rate of the interconversion of the atropisomers of compound 1.…”

“…In general, interconversion of atropisomers does not depend greatly upon pH or additives; however, in the past, we have occasionally encountered some unusual exceptions to this rule. 11 In the present case, we found no effect of additives (triethylamine and acetic acid) or aqueous buffer of different pH (3, 7, and 10) on the rate of the interconversion of the atropisomers of compound 1.…”

High throughput analysis enables high throughput experimentation in pharmaceutical process research

“…This close working relationship with cutting edge instrument developers became a key component of our strategy for success, allowing us to shape and guide commercial product development in ways that maximized research productivity. The net result of the introduction of the prep chiral SFC resolution platform was that various strategies for enantioselective synthesis, 34 diastereocontrol, kinetic resolution 35 or checking propensity for racemization [36][37][38][39] could be quickly explored by project chemists, allowing competing synthetic routes to be rapidly evaluated and differentiated. This strategy also proved useful for researchers in drug metabolism, 40 and especially for medicinal chemists, where the work on a candidate for treatment of Alzheimer's disease nicely illustrates the value of the approach.…”

9.06 The Use of Preparative Chiral Chromatography for Accessing Enantiopurity in Pharmaceutical Discovery and Development

“…molecular switch elements. 69 Recently, preparative chromatography has also begun to be used in the investigation into new ligands and catalysts for use in enantioselective synthesis. Prof. Gregory Fu has been an early adopter of this technology, using rapid chromatographic enantioseparation to enable rapid prototyping of new catalyst families.…”