Automated synthesis platforms accelerate and simplify the preparation of molecules by removing the physical barriers to organic synthesis. This provides unrestricted access to biopolymers and small ...molecules via reproducible and directly comparable chemical processes. Current automated multistep syntheses rely on either iterative
or linear processes
, and require compromises in terms of versatility and the use of equipment. Here we report an approach towards the automated synthesis of small molecules, based on a series of continuous flow modules that are radially arranged around a central switching station. Using this approach, concise volumes can be exposed to any reaction conditions required for a desired transformation. Sequential, non-simultaneous reactions can be combined to perform multistep processes, enabling the use of variable flow rates, reuse of reactors under different conditions, and the storage of intermediates. This fully automated instrument is capable of both linear and convergent syntheses and does not require manual reconfiguration between different processes. The capabilities of this approach are demonstrated by performing optimizations and multistep syntheses of targets, varying concentrations via inline dilutions, exploring several strategies for the multistep synthesis of the anticonvulsant drug rufinamide
, synthesizing eighteen compounds of two derivative libraries that are prepared using different reaction pathways and chemistries, and using the same reagents to perform metallaphotoredox carbon-nitrogen cross-couplings
in a photochemical module-all without instrument reconfiguration.
Ultrastrong, smooth, and shiny graphene paper with a layered structure (see figure) is prepared by vacuum filtration of a well‐dispersed graphene dispersion. Moderate thermal annealing further ...enhances its mechanical properties and electrical conductivity. A combination of exceptional mechanical strength, thermal stability, high electrical conductivity, and biocompability makes this unique material promising for many technological applications.
Abstract The brain is an enormously complex organ structured into various regions of layered tissue. Researchers have attempted to study the brain by modeling the architecture using two dimensional ...(2D) in vitro cell culturing methods. While those platforms attempt to mimic the in vivo environment, they do not truly resemble the three dimensional (3D) microstructure of neuronal tissues. Development of an accurate in vitro model of the brain remains a significant obstacle to our understanding of the functioning of the brain at the tissue or organ level. To address these obstacles, we demonstrate a new method to bioprint 3D brain-like structures consisting of discrete layers of primary neural cells encapsulated in hydrogels. Brain-like structures were constructed using a bio-ink consisting of a novel peptide-modified biopolymer, gellan gum-RGD (RGD-GG), combined with primary cortical neurons. The ink was optimized for a modified reactive printing process and developed for use in traditional cell culturing facilities without the need for extensive bioprinting equipment. Furthermore the peptide modification of the gellan gum hydrogel was found to have a profound positive effect on primary cell proliferation and network formation. The neural cell viability combined with the support of neural network formation demonstrated the cell supportive nature of the matrix. The facile ability to form discrete cell-containing layers validates the application of this novel printing technique to form complex, layered and viable 3D cell structures. These brain-like structures offer the opportunity to reproduce more accurate 3D in vitro microstructures with applications ranging from cell behavior studies to improving our understanding of brain injuries and neurodegenerative diseases.
Solid reagents, leaching catalysts, and heterogeneous photocatalysts are commonly employed in batch processes but are ill‐suited for continuous‐flow chemistry. Heterogeneous catalysts for thermal ...reactions are typically used in packed‐bed reactors, which cannot be penetrated by light and thus are not suitable for photocatalytic reactions involving solids. We demonstrate that serial micro‐batch reactors (SMBRs) allow for the continuous utilization of solid materials together with liquids and gases in flow. This technology was utilized to develop selective and efficient fluorination reactions using a modified graphitic carbon nitride heterogeneous catalyst instead of costly homogeneous metal polypyridyl complexes. The merger of this inexpensive, recyclable catalyst and the SMBR approach enables sustainable and scalable photocatalysis.
A flow system for processing solids enables the efficient and scalable utilization of heterogeneous photocatalysis for selective fluorinations.
The development of cell printing is vital for establishing biofabrication approaches as clinically relevant tools. Achieving this requires bio-inks which must not only be easily printable, but also ...allow controllable and reproducible printing of cells. This review outlines the general principles and current progress and compares the advantages and challenges for the most widely used biofabrication techniques for printing cells: extrusion, laser, microvalve, inkjet and tissue fragment printing. It is expected that significant advances in cell printing will result from synergistic combinations of these techniques and lead to optimised resolution, throughput and the overall complexity of printed constructs.
Reliable glycosylation reactions that allow for the stereo- and regioselective installation of glycosidic linkages are paramount to the chemical synthesis of glycan chains. The stereoselectivity of ...glycosylations is exceedingly difficult to control due to the reaction’s high degree of sensitivity and its shifting, simultaneous mechanistic pathways that are controlled by variables of unknown degree of influence, dominance, or interdependency. An automated platform was devised to quickly, reproducibly, and systematically screen glycosylations and thereby address this fundamental problem. Thirteen variables were investigated in as isolated a manner as possible, to identify and quantify inherent preferences of electrophilic glycosylating agents (glycosyl donors) and nucleophiles (glycosyl acceptors). Ways to enhance, suppress, or even override these preferences using judicious environmental conditions were discovered. Glycosylations involving two specific partners can be tuned to produce either 11:1 selectivity of one stereoisomer or 9:1 of the other by merely changing the reaction conditions.
Unprotected α-amino carbon radicals are produced as novel intermediates via a transformation that merges acid-promoted N–H imine generation and chemoselective photocatalytic single-electron ...reduction. Coupling ammonia and aldehydes/ketones allows the generation of primary amines under mild conditions without the need for protecting groups. The key intermediate can be efficiently transformed into primary (di)amines by a formal dimerization, reductive amination via hydrogen atom transfer, and arylation through radical–radical coupling.
Continuous Flow Photochemistry Gilmore, Kerry; Seeberger, Peter H.
Chemical record,
June 2014, Letnik:
14, Številka:
3
Journal Article
Recenzirano
Due to the narrow width of tubing/reactors used, photochemistry performed in micro‐ and mesoflow systems is significantly more efficient than when performed in batch due to the Beer‐Lambert Law. ...Owing to the constant removal of product and facility of flow chemical scalability, the degree of degradation observed is generally decreased and the productivity of photochemical processes is increased. In this Personal Account, we describe a wide range of photochemical transformations we have examined using both visible and UV light, covering cyclizations, intermolecular couplings, radical polymerizations, as well as singlet oxygen oxygenations.
The efforts of the Seeberger group in continuous photochemical reactions, both visible and UV light, are described. These transformations include cyclizations, intermolecular couplings, radical polymeriztions, as well as a range of singlet oxygen oxygenations.
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