Copper-Catalyzed Racemization-Recycle of a Quaternary Center and Optimization Using a Combined Kinetics-DoE/MLR Modeling Approach.

The copper-catalyzed racemization of a complex, quaternary center of a key intermediate on route to lanabecestat has been identified. Optimization and mechanistic understanding were achieved through the use of an efficient, combined kinetic-multiple linear regression approach to experimental design and modeling. The use of a definitive screening design with mechanistically relevant factors and a mixture of fitted kinetic descriptors and empirical measurements facilitated the generation of a model that accurately predicted complex reaction time course behavior.

Tautomerism troubles: proton transfer modifies the stereochemical assignments in diastereoisomeric structures of spiro-cyclic 5-methyl-2-imidazol-4-amine dimers.

During the racemization of a novel pharmaceutical spiro-cyclic imidazole-amine compound, namely, 6'-bromo--(6'-bromo-4-meth-oxy-4''-methyl-3'-di-spiro[cyclo-hexane-1,2'-indene-1',2''-imidazol]-5''-yl)-4-meth-oxy-4''-methyl-3'-di-spiro-[cyclo-hexane-1,2'-indene-1',2''-imidazol]-5''-imine, CHBrNO, two impurities were isolated. These impurities were clearly dimers from mass spectroscopic analysis, however single-crystal diffraction characterization was required for the assignment of stereochemistry. The single-crystal diffraction results revealed subtly different structures to those proposed, due to an unexpected proton transfer.

Tuning for rate and duration of frequency-modulated sweeps in the mammalian inferior colliculus.

Responses of auditory duration-tuned neurons (DTNs) are selective for stimulus duration. We used single-unit extracellular recording to investigate how the inferior colliculus (IC) encodes frequency-modulated (FM) sweeps in the big brown bat. It was unclear whether the responses of so-called "FM DTNs" encode signal duration, like classic pure-tone DTNs, or the FM sweep rate.

Organization and trade-off of spectro-temporal tuning properties of duration-tuned neurons in the mammalian inferior colliculus.

Neurons throughout the mammalian central auditory pathway respond selectively to stimulus frequency and amplitude, and some are also selective for stimulus duration. First found in the auditory midbrain or inferior colliculus (IC), these duration-tuned neurons (DTNs) provide a potential neural mechanism for encoding temporal features of sound. In this study, we investigated how having an additional neural response filter, one selective to the duration of an auditory stimulus, influences frequency tuning and neural organization by recording single-unit responses and measuring the dorsal-ventral position and spectral-temporal tuning properties of auditory DTNs from the IC of the awake big brown bat (Eptesicus fuscus).