One-pot Dess-Martin periodinane-mediated oxidative deprotection and olefination of trimethylsilyl-protected pyranosides and pyranoses.

The selective functionalization of carbohydrates provides a powerful method for introducing structural complexity, allowing access to unique drug scaffolds with distinctive pharmaceutical profiles. Herein, we describe an efficient and selective carbon-carbon bond forming reaction of a variety of common trimethylsilyl-protected pyranosides and pyranoses at C-6 using a one-pot Dess-Martin periodinane-mediated oxidation deprotection. This is followed by addition of stabilized and non-stabilized ylides to generate alkenoate carbohydrates and related analogs in good to moderate yields. We also report on the rapid deprotection of the remaining trimethylsilyl ether groups in near quantitative yields using an acidic resin-mediated ethanolysis.

Rehabilitation Exergames: Use of Motion Sensing and Machine Learning to Quantify Exercise Performance in Healthy Volunteers.

BACKGROUND: Performing physiotherapy exercises in front of a physiotherapist yields qualitative assessment notes and immediate feedback. However, practicing the exercises at home lacks feedback on how well patients are performing the prescribed tasks. The absence of proper feedback might result in patients performing the exercises incorrectly, which could worsen their condition. We present an approach to generate performance scores to enable tracking the progress by both the patient at home and the physiotherapist in the clinic. OBJECTIVE: This study aims to propose the use of 2 machine learning algorithms, dynamic time warping (DTW) and hidden Markov model (HMM), to quantitatively assess the patient's performance with respect to a reference. METHODS: Movement data were recorded using a motion sensor (Kinect V2), capable of detecting 25 joints in the human skeleton model, and were compared with those of a reference. A total of 16 participants were recruited to perform 4 different exercises: shoulder abduction, hip abduction, lunge, and sit-to-stand exercises. Their performance was compared with that of a physiotherapist as a reference. RESULTS: Both algorithms showed a similar trend in assessing participant performance. However, their sensitivity levels were different. Although DTW was more sensitive to small changes, HMM captured a general view of the performance, being less sensitive to the details. CONCLUSIONS: The chosen algorithms demonstrated their capacity to objectively assess the performance of physical therapy. HMM may be more suitable in the early stages of a physiotherapy program to capture and report general performance, whereas DTW could be used later to focus on the details. The scores enable the patient to monitor their daily performance. They can also be reported back to the physiotherapist to track and assess patient progress, provide feedback, and adjust the exercise program if needed.

Band-selective excitation NMR spectroscopy and quantitative time-domain analysis using Complete Reduction to Amplitude-Frequency Table (CRAFT) to determine distribution coefficients during drug development.

A sensitive quantitative 1 H NMR method for determining distribution or partition coefficients has been developed that is applicable to early drug discovery. After partitioning and equilibration, aliquots from each layer are analyzed using band-selective excitation 1 H NMR spectroscopy in regions that are free of 1-octanol and water solvent signals. Signals are quantitated directly using CRAFT software, and their amplitudes are adjusted to correct for nonuniformity within the excitation band. Using this approach, the distribution coefficients for 20 drugs present at low concentrations were determined giving values that were in excellent agreement with literature values.

Dissolved organic matter processing and photoreactivity in a wastewater treatment constructed wetland.

Constructed wetlands have the capacity to degrade a host of contaminants of emerging concern through photodegradation via sunlight produced reactive oxygen species. Dissolved organic matter (DOM) is a critical intermediary in photodegradation as it influences the production of reactive oxygen species. In this study, the photochemical behavior of DOM of wastewater treated in constructed wetlands was characterized. Whole water samples and fractionated DOM were characterized using SUVA254, spectral slope ratios, excitation emission matrix fluorescence spectroscopy (EEMs), and proton nuclear magnetic resonance (1H NMR). Photoreactivity was assessed by measuring formation rates and steady state concentrations of hydroxyl radical (•OH), singlet oxygen (1O2), and the triplet excited states of DOM (3DOM⁎). The effluent was observed to transition from a microbially sourced protein-like DOM to a terrestrial DOM with higher aromaticity. Size exclusion chromatography revealed an 18% increase in larger molecular weight fractions of vegetated wetland effluent DOM. Additionally, wetland effluent DOM was observed to have a 32% increase in the aromatic region of 1H NMR spectra as compared to untreated wastewater. 1H NMR analysis also indicated an increase in the complexity of wetland effluent DOM. Fluorescence intensity fraction of the protein-like Peak T (Ex/Em:278/342 nm) of EEMs decreased by 16% from the untreated wastewater to wetland effluent. A negative correlation between the percent fluorescence of Peak T (Ex/Em:278/342 nm) and Peaks A (Ex/Em:245/460 nm), C (Ex/Em:336/435 nm), and M (Ex/Em:312/400 nm) of the excitation emission spectra confirmed the transition from a spectrum of pure wastewater to a spectrum characteristic of terrestrially derived DOM. Microbial uptake of bio-labile DOM and leaching of humic like substances from vegetated wetland cells were the predominant processes involved in this transition. This transition coincided with an increase in the formation rates of 1O2 and 3DOM⁎ and in the steady state concentration of 1O2.

Determination of partition coefficients using 1 H NMR spectroscopy and time domain complete reduction to amplitude-frequency table (CRAFT) analysis.

We have developed a simple, direct and novel method for the determination of partition coefficients and partitioning behavior using 1 H NMR spectroscopy combined with time domain complete reduction to amplitude-frequency tables (CRAFT). After partitioning into water and 1-octanol using standard methods, aliquots from each layer are directly analyzed using either proton or selective excitation NMR experiments. Signal amplitudes for each compound from each layer are then extracted directly from the time domain data in an automated fashion and analyzed using the CRAFT software. From these amplitudes, log P and log D7.4 values can be calculated directly. Phase, baseline and internal standard issues, which can be problematic when Fourier transformed data are used, are unimportant when using time domain data. Furthermore, analytes can contain impurities because only a single resonance is examined and need not be UV active. Using this approach, we examined a variety of pharmaceutically relevant compounds and determined partition coefficients that are in excellent agreement with literature values. To demonstrate the utility of this approach, we also examined salicylic acid in more detail demonstrating an aggregation effect as a function of sample loading and partition coefficient behavior as a function of pH value. This method provides a valuable addition to the medicinal chemist toolbox for determining these important constants. Copyright © 2017 John Wiley & Sons, Ltd.