Chromatographic resolution of atropisomers for toxicity and biotransformation studies in pharmaceutical research.

Atropisomerism can be a complex concept for those who have not encountered it before. This paper discusses the experiments for identification, isolation, thermal stability, toxicity and biotransformation of various species. The identified atropisomers are a series of rotational hindered biaryl, rotational hindered amide, ring flip, and macrocycles atropisomers identified using supercritical fluid chromatography (SFC) and high performance liquid chromatography (HPLC).

Evolution of strategies to achieve baseline separation of ten anionic, water-soluble sulfated estrogens via achiral packed column supercritical fluid chromatography.

Near baseline separation of ten sulfated sodium salts of various structurally related estrogens employing a variety of bonded stationary phase packed columns was obtained using a conventional supercritical fluid chromatograph coupled with UV detection. Critical pairs 2/3 (8,9-dehydroestrone/17β-dihydroequilin) and 6/7 (17α-estradiol or 17α-dihydroequilin/estrone), however, failed to baseline separate. In all preliminary separations, 10mM ammonium acetate and variable percentages of H2O were initially used as co-additives in conjunction with methanol as a modifier.

Carbonyldiimidazole-mediated Lossen rearrangement.

Carbonyldiimidazole (CDI) was found to mediate the Lossen rearrangement of various hydroxamic acids to isocyanates. This process is experimentally simple and mild, with imidazole and CO(2) being the sole stoichiometric byproduct. Significant for large-scale application, the method avoids the use of hazardous reagents and thus represents a green alternative to standard processing conditions for the Curtius and Hofmann rearrangements.