Heinmcintyre7463

© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Cys is present in a large number of biomolecules and other synthetic molecules.  Although the thiol side chain of Cys can be in a free form, in most cases it forms a disulfide bond either with a second Cys (bridge) or with another thiol, as in the case of the protecting group.  Efficient reduction of these disulfide bridges is a requirement for many applications of Cys-containing molecules in the biochemical and organic chemistry arenas.  Here we review reducing methods for disulfide bonds, taking into consideration the solubility of the substrates when selecting the appropriate reducing reagent. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Because both diarrhea due to other causes and gastrointestinal colonization with toxigenic Clostridioides difficile are common in HSCT, there is a possibility of false-positive diagnoses of C difficile infections (CDI). METHODS We estimated the probability of a patient being colonized by toxigenic C difficile by testing non-diarrheal surveillance stools from 223 HSCT recipients and the probability that a specimen submitted for C difficile testing was not CDI by determining the number of clinical tests that returned negative from this cohort. The number of expected false-positive CDI was estimated using these probabilities and compared with observed clinical test results. RESULTS The expected false-positive and the observed numbers of positive clinical results were similar. The 20 patients diagnosed with CDI were also similar to 142 patients with diarrhea and C difficile-negative stools in number of stools on day of testing, associated symptoms, and the recorded number of days to formed stools. C difficile colonization was most commonly detected during the first week and CDI during the second. Retrospective analysis of 837 patients showed that 18 stools were submitted for each diagnosis of CDI. Ribotyping of the surveillance samples showed 17 ribotypes. CONCLUSIONS Although several assumptions could impact the accuracy of our false-positive CDI estimates, it appears that many HSCT recipients diagnosed with CDI may actually represent colonized status and an alternative cause of diarrhea. Diagnostic stewardship, including limiting CDI diagnoses to patients with positive toxin and restricting stool submissions to patients with more severe symptoms, may decrease the number of false-positive diagnoses. This article is protected by copyright. All rights reserved.This prospective observational study analyzed the pharmacokinetics of busulfan in Japanese children and evaluated the predicting accuracy of previous pediatric PPK models of busulfan. This study enrolled five patients (aged 2-12 years, BW 14-48 kg) receiving a busulfan-based conditioning regimen for hematopoietic stem cell transplantation at our hospital between January 2017 and December 2018. All patients received a 2-hour intravenous busulfan infusion four times daily for a total of 16 doses. After the infusions, 51 plasma samples were collected with the plasma busulfan concentration measured by liquid chromatography-tandem mass spectrometry. PPK model fitting was analyzed using the (%MPE) and the (%MAPE). Limited sampling strategies for estimating busulfan AUC were also evaluated. High interpatient variability was observed in the PK parameters. The most suitable PPK model that reflected our data was McCune's two-compartment model (%MPE -8.7, %MAPE 19.3). A combination sampling method using the busulfan concentration at 2 and 6 hours after the start of the first busulfan dose was found to be able to estimate AUC4 day . These results provide useful information on busulfan therapeutic drug monitoring in the Japanese pediatric population. © 2020 Wiley Periodicals, Inc.Processes leading to enantiomerically pure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, crystallization-induced diastereomeric transformation allows in theory for 100 % transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. Herein, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We report a new general single thermodynamic deracemization process based on cocrystallization for the deracemization of (R,S)-4,4-dimethyl-1-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)pentan-3-one. GDC-6036 chemical structure This study demonstrates the feasibility of this novel approach and paves the way to further development of such processes. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.A straightforward methodology for the synthesis of anti-Markovnikov-type alcohols is presented. Using a specific cobalt triphos complex in the presence of Zn(OTf) 2 as additive, the hydrogenation of epoxides proceeds with high yields and selectivit ies . The described protocol shows a broad substrate scope , including multi-substituted internal and terminal epoxides , as well as a good functional group tolerance. V arious natural product derivatives including steroids, terpenoids and sesquiterpenoids gave access to the corresponding alcohols in moderate to excellent yields. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Metal-coordinating directing groups have seen extensive use in the field of transition-metal-catalysed alkene functionalization; however, their waste-generating installation and removal steps limit the efficiency and practicality of reactions that rely on their use. Inspired by developments in asymmetric organocatalysis, where reactions rely on reversible covalent interactions between an organic substrate and a chiral mediator, herein we report a transient directing group approach to reductive Heck hydroarylation of alkenyl benzaldehyde substrates that proceeds under mild conditions. Highly stereoselective migratory insertion is facilitated by in situ formation of an imine from catalytic amounts of commercially available amino acid additive. Computational studies reveal an unusual mode of enantioinduction by the remote chiral centre in the transient directing group. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.