Synthesis of deoxymannojirimycin using a Ruthenium-catalysed hydrogen borrowing reaction

<p>1-Deoxymannojirimycin (DMJ) has been investigated as a potential anti-cancer therapy due to its specific inhibition of class I α-mannosidase enzymes, which has been shown to trigger ER stress and the Unfolded Protein Response (UPR) pathway, leading to apoptosis in human hepatocarcinoma cells. Current methods for the synthesis of DMJ consist of multiple steps and often result in poor yields. The objectives of this research project were to develop a scale-up suitable synthesis of deoxymannojirimycin (DMJ), and to assess the feasibility of telescoping key-reactions to reduce the number of unit operations. Synthetic efforts focused on the key conversion of 1 to 2 have previously involved separate oxidation and reduction steps. In our laboratory; attempts to use hydrogen-borrowing chemistry had taken >48hr and not been achieved in high yield. The highlights of this work were that this conversion was ultimately realised in 95% yield in 24hr, and that the final deprotection of (2) could be telescoped into the process removing reaction-workup and chromatographic steps. The ruthenium catalyst used in the hydrogen borrowing reaction was found to be extremely air-sensitive, with reactions taking place in carefully prepared reaction vessels under an atmosphere of dry argon gas. The catalyst was also found to exhibit sensitivities to materials such as metal needles and polymer tubing, preventing sampling and monitoring of the reaction during synthesis. This study demonstrated that a one-pot synthesis is feasible,compressing the final steps in the synthesis of DMJ in excellent yield. The difficulty arises from the sensitive nature of the ruthenium catalyst, and the extreme care required in the preparation of the glassware and reagents used in synthesis. Many aspects of this development require further investigation, including the sampling, monitoring and quality control of each synthetic step.</p>

Synthesis of deoxymannojirimycin using a Ruthenium-catalysed hydrogen borrowing reaction

<p>1-Deoxymannojirimycin (DMJ) has been investigated as a potential anti-cancer therapy due to its specific inhibition of class I α-mannosidase enzymes, which has been shown to trigger ER stress and the Unfolded Protein Response (UPR) pathway, leading to apoptosis in human hepatocarcinoma cells. Current methods for the synthesis of DMJ consist of multiple steps and often result in poor yields. The objectives of this research project were to develop a scale-up suitable synthesis of deoxymannojirimycin (DMJ), and to assess the feasibility of telescoping key-reactions to reduce the number of unit operations. Synthetic efforts focused on the key conversion of 1 to 2 have previously involved separate oxidation and reduction steps. In our laboratory; attempts to use hydrogen-borrowing chemistry had taken >48hr and not been achieved in high yield. The highlights of this work were that this conversion was ultimately realised in 95% yield in 24hr, and that the final deprotection of (2) could be telescoped into the process removing reaction-workup and chromatographic steps. The ruthenium catalyst used in the hydrogen borrowing reaction was found to be extremely air-sensitive, with reactions taking place in carefully prepared reaction vessels under an atmosphere of dry argon gas. The catalyst was also found to exhibit sensitivities to materials such as metal needles and polymer tubing, preventing sampling and monitoring of the reaction during synthesis. This study demonstrated that a one-pot synthesis is feasible,compressing the final steps in the synthesis of DMJ in excellent yield. The difficulty arises from the sensitive nature of the ruthenium catalyst, and the extreme care required in the preparation of the glassware and reagents used in synthesis. Many aspects of this development require further investigation, including the sampling, monitoring and quality control of each synthetic step.</p>

Novel Platform for Regulation of Extracellular Vesicles and Metabolites Secretion from Cells Using a Multi-Linkable Horizontal Co-Culture Plate

Microfluidics is applied in biotechnology research via the creation of microfluidic channels and reaction vessels. Filters are considered to be able to simulate microfluidics. A typical example is the cell culture insert, which comprises two vessels connected by a filter. Cell culture inserts have been used for years to study cell-to-cell communication. These systems generally have a bucket-in-bucket structure and are hereafter referred to as a vertical-type co-culture plate (VTCP). However, VTCPs have several disadvantages, such as the inability to simultaneously observe samples in both containers and the inability of cell-to-cell communication through the filters at high cell densities. In this study, we developed a novel horizontal-type co-culture plate (HTCP) to overcome these disadvantages and confirm its performance. In addition, we clarified the migration characteristics of substances secreted from cells in horizontal co-culture vessels. It is generally assumed that less material is exchanged between the horizontal vessels. However, the extracellular vesicle (EV) transfer was found to be twice as high when using HTCP. Other merits include control of the degree of co-culture via the placement of cells. We believe that this novel HTCP container will facilitate research on cell-to-cell communication in various fields.

Optimization and Validation of Rancimat Operational Parameters to Determine Walnut Oil Oxidative Stability

This study was performed to optimize and validate Rancimat (Metrohm Ltd., Herisau, Switzerland) operational parameters including temperature, air-flow, and sample weight to minimize Induction-Time (IT) and IT-Coefficient-of-Variation (CV), using Response Surface Methodology (RSM). According to a Box–Behnken experimental design, walnut oil equivalent to 3-, 6-, or 9-g was added to each reaction vessel and heated to 100, 110, or 120 °C, while an air-flow equal to 10-, 15-, or 20-L·h−1 was forced through the reaction vessels. A stationary point was found per response variable (IT and CV), and optimal parameters were defined considering the determined stationary points for both response variables at 100 °C, 25 L·h−1, and 3.9 g. Optimal parameters provided an IT of 5.42 ± 0.02 h with a CV of 1.25 ± 0.83%. RSM proved to be a useful methodology to find Rancimat operational parameters that translate to accurate and efficient values of walnut oil IT.

Nanomaterials Synthesis through Microfluidic Methods: An Updated Overview

Microfluidic devices emerged due to an interdisciplinary “collision” between chemistry, physics, biology, fluid dynamics, microelectronics, and material science. Such devices can act as reaction vessels for many chemical and biological processes, reducing the occupied space, equipment costs, and reaction times while enhancing the quality of the synthesized products. Due to this series of advantages compared to classical synthesis methods, microfluidic technology managed to gather considerable scientific interest towards nanomaterials production. Thus, a new era of possibilities regarding the design and development of numerous applications within the pharmaceutical and medical fields has emerged. In this context, the present review provides a thorough comparison between conventional methods and microfluidic approaches for nanomaterials synthesis, presenting the most recent research advancements within the field.

Standardized Stirring for Small Scale Surveys

Stirring rates in heterogeneous catalytic reactions have an effect on reaction rates. When conducting small-scale surveys using a single central stir plate, reaction vessels in different positions experience slightly different levels and patterns of agitation. We probed this effect by running the same reaction 40 times, varying the stir rate (fast/slow) and the vial position using two 3D printed vial holders. We found variability of conversion (measured mass spectrometrically) to be approximately two times higher for vials placed at different distances, but the effect was relatively small and could be minimized by using a high stir rate. For those experimenters wishing to completely eliminate differential stirring as a cause for variation in results, the 3D printed circular array we designed is recommended over a conventional rectangular array.

A 3D-Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox- & Photoelectrochemical Synthesis

Most published photochemical reactions are still not performed under standardized conditions. It is well known that the control of light intensity, the exact reaction temperature and other parameters are crucial for the success of a photochemical reaction. However, for most reactions reported in the literature, these parameters are not precisely controlled and recorded. As a result, the reproduction of these reactions is difficult and the progress in the field of photoredox chemistry is hampered by this limitation. To address this problem, a 3D-printed photoreactor was designed which can be easily replicated with a small number of inexpensive and easily available components. Equipped with thermoelectric coolers, the reactor can access and precisely control the temperature in the range of -17 °C to 80 °C, while reactions under high-intensity irradiation are performed with LED lamps from Kessil or HepatoChem. The practical design of the vial holder allows a versatile use of different reaction vessels - in addition to fast reaction optimization with up to eight vials simultaneously, upscaling in batch and flow is easily possible. Due to the high light intensity, the catalyst loading can be reduced to 0.1 mol% for large-scale reactions. The flexibility of the vial holder is demonstrated by combining IKA’s ElectraSyn 2.0 with the photoreactor to perform photoelectrochemical reactions in a reproducible manner.<br>

A 3D-Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox- & Photoelectrochemical Synthesis

Most published photochemical reactions are still not performed under standardized conditions. It is well known that the control of light intensity, the exact reaction temperature and other parameters are crucial for the success of a photochemical reaction. However, for most reactions reported in the literature, these parameters are not precisely controlled and recorded. As a result, the reproduction of these reactions is difficult and the progress in the field of photoredox chemistry is hampered by this limitation. To address this problem, a 3D-printed photoreactor was designed which can be easily replicated with a small number of inexpensive and easily available components. Equipped with thermoelectric coolers, the reactor can access and precisely control the temperature in the range of -17 °C to 80 °C, while reactions under high-intensity irradiation are performed with LED lamps from Kessil or HepatoChem. The practical design of the vial holder allows a versatile use of different reaction vessels - in addition to fast reaction optimization with up to eight vials simultaneously, upscaling in batch and flow is easily possible. Due to the high light intensity, the catalyst loading can be reduced to 0.1 mol% for large-scale reactions. The flexibility of the vial holder is demonstrated by combining IKA’s ElectraSyn 2.0 with the photoreactor to perform photoelectrochemical reactions in a reproducible manner.<br>

A 3D-Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox- & Photoelectrochemical Synthesis

Most published photochemical reactions are still not performed under standardized conditions. It is well known that the control of light intensity, the exact reaction temperature and other parameters are crucial for the success of a photochemical reaction. However, for most reactions reported in the literature, these parameters are not precisely controlled and recorded. As a result, the reproduction of these reactions is difficult and the progress in the field of photoredox chemistry is hampered by this limitation. To address this problem, a 3D-printed photoreactor was designed which can be easily replicated with a small number of inexpensive and easily available components. Equipped with thermoelectric coolers, the reactor can access and precisely control the temperature in the range of -17 °C to 80 °C, while reactions under high-intensity irradiation are performed with LED lamps from Kessil or HepatoChem. The practical design of the vial holder allows a versatile use of different reaction vessels - in addition to fast reaction opMost published photochemical reactions are still not performed under standardized conditions. It is well known that the control of light intensity, the exact reaction temperature and other parameters are crucial for the success of a photochemical reaction. However, for most reactions reported in the literature, these parameters are not precisely controlled and recorded. As a result, the reproduction of these reactions is difficult and the progress in the field of photoredox chemistry is hampered by this limitation. To address this problem, a 3D-printed photoreactor was designed which can be easily replicated with a small number of inexpensive and easily available components. Equipped with thermoelectric coolers, the reactor can access and precisely control the temperature in the range of -17 °C to 80 °C, while reactions under high-intensity irradiation are performed with LED lamps from Kessil or HepatoChem. The practical design of the vial holder allows a versatile use of different reaction vessels - in addition to fast reaction optimization with up to eight vials simultaneously, upscaling in batch and flow is easily possible. Due to the high light intensity, the catalyst loading can be reduced to 0.1 mol% for large-scale reactions. The flexibility of the vial holder is demonstrated by combining IKA’s ElectraSyn 2.0 with the photoreactor to perform photoelectrochemical reactions in a reproducible manner.timization with up to eight vials simultaneously, upscaling in batch and flow is easily possible. Due to the high light intensity, the catalyst loading can be reduced to 0.1 mol% for large-scale reactions. The flexibility of the vial holder is demonstrated by combining IKA’s ElectraSyn 2.0 with the photoreactor to perform photoelectrochemical reactions in a reproducible manner.

Standardized Stirring for Small Scale Surveys

Stirring rates in heterogeneous catalytic reactions have an effect on reaction rates. When conducting small-scale surveys using a single central stir plate, reaction vessels in different positions experience slightly different levels and patterns of agitation. We probed this effect by running the same reaction 40 times, varying the stir rate (fast/slow) and the vial position using two 3D printed vial holders. We found variability of conversion (measured mass spectrometrically) to be approximately two times higher for vials placed at different distances, but the effect was relatively small and could be minimized by using a high stir rate. For those experimenters wishing to completely eliminate differential stirring as a cause for variation in results, the 3D printed circular array we designed is recommended over a conventional rectangular array.