The tandem radical route to indole alkaloids: an unusual rearrangement reaction

Cyclisation of the precursor 6 under standard radical conditions yields the tetracyclic structure 7 which represents the core of a number of indole alkaloids along with the novel tetracycle 13

Design and development of 3D printed catalytically-active stirrers for chemical synthesis

In this present study, we describe the novel design, preparation and evaluation of catalyst-impregnated stirrer beads for chemical synthesis. Using a low-cost SLA 3D printer and freeware design software, a high surface area holder for a magnetic stirrer bead was developed and 3D printed containing p-toluenesulfonic acid. The devices were used to efficiently catalyze Mannich reactions in excellent yields and it was demonstrated that the devices can be re-used up to 5-times with excellent reproducibility

Intramolecular Acylal Cyclisation (IAC) as an Efficient Synthetic Strategy towards the Total Synthesis of Erythrina Alkaloid Derivatives

Compounds that comprise the erythrina alkaloid class of natural products are based on a tetracyclic spiroamine framework and exhibit a range of biological activities on the central nervous system. Herein, we report a new and efficient total synthesis of this multiple-ring system based on an intramolecular acylal cyclisation (IAC) approach. Using this methodology, the tetracyclic core was rapidly assembled over a two-step domino process catalysed by a Lewis acid. The effect of heteroatoms, substituents and ring size on the IAC has also been investigated, and the broad application of this procedure is demonstrated by the synthesis of a library of derivatives in good yields with excellent regioselectivity

Extending practical flow chemistry into the undergraduate curriculum via the use of a portable low-cost 3D printed continuous flow system

Continuous flow chemistry is undergoing rapid growth and adoption within the pharmaceutical industry due to its ability to rapidly translate chemical discoveries from medicinal chemistry laboratories into process laboratories. Its growing significance means that it is imperative that flow chemistry is taught and experienced by both undergraduate and postgraduate synthetic chemists. However, whilst flow chemistry has been incorporated by industry, there remains a distinct lack of practical training and knowledge at both undergraduate and postgraduate levels. A key challenge associated with its implementation is the high cost (>$25,000) of the system’s themselves, which is far beyond the financial reach of most universities and research groups, meaning that this key technology remains open to only a few groups and that its associated training remains a theoretical rather than a practical subject. In order to increase access to flow chemistry, we sought to design and develop a small-footprint, low-cost and portable continuous flow system that could be used to teach flow chemistry, but that could also be used by research groups looking to transition to continuous flow chemistry. A key element of its utility focusses on its 3D printed nature, as low-cost reactors could be readily incorporated and modified to suit differing needs and educational requirements. In this paper, we demonstrate the system’s flexibility using reactors and mixing chips designed and 3D printed by an undergraduate project student (N.T.) and show how the flexibility of the system allows the investigation of differing flow paths on the same continuous flow system in parallel

A Common Precursor Approach to Structurally Diverse Natural Products: The Synthesis of the Core Structure of (±)-Clausenamide and the Total Synthesis of (±)-Hyalodendrin

Structurally diverse natural products from unrelated sources typically require the development of individual synthetic routes. In a novel approach, we have shown that the epidithiodiketopiperazine-derived natural product (±)-hyalodendrin and the core structure of the unrelated pyrrolidine-derived natural product clausenamide can be synthesised from a common synthetic precursor in good yield by simple variation of the reaction conditions

Confocal laser scanning, scanning electron, and transmission electron microscopy investigation of Enterococcus faecalis biofilm degradation using passive and active sodium hypochlorite irrigation within a simulated root canal model

Root canal irrigation is an important adjunct to control microbial infection. The aim of this study was to investigate the effect of 2.5% (wt/vol) sodium hypochlorite (NaOCl) agitation on the removal, killing, and degradation of Enterococcus faecalis biofilm. A total of 45 root canal models were manufactured using 3D printing with each model comprising an 18 mm length simulated root canal of apical size 30 and taper 0.06. E. faecalis biofilms were grown on the apical 3 mm of the models for 10 days. A total of 60 s of 9 ml of 2.5% NaOCl irrigation using syringe and needle was performed, the irrigant was either left stagnant in the canal or agitated using manual (Gutta-percha), sonic, and ultrasonic methods for 30 s. Following irrigation, the residual biofilms were observed using confocal laser scanning, scanning electron, and transmission electron microscopy. The data were analyzed using one-way ANOVA with Dunnett post hoc tests at a level of significance p ≤ .05. Consequence of root canal irrigation indicate that the reduction in the amount of biofilm achieved with the active irrigation groups (manual, sonic, and ultrasonic) was significantly greater when compared with the passive and untreated groups (p < .05). Collectively, finding indicate that passive irrigation exhibited more residual biofilm on the model surface than irrigant agitated by manual or automated (sonic, ultrasonic) methods. Total biofilm degradation and nonviable cells were associated with the ultrasonic group

Physiological signature of a novel potentiator of AMPA receptor signalling.

We have synthesized a novel small molecule based on the pyrrolidinone-containing core structure of clausenamide, which is a candidate anti-dementia drug. The synthetic route yielded multi-gram quantities of an isomeric racemate mixture in a short number of steps. When tested in hippocampal slices from young adult rats the compound enhanced AMPA receptor-mediated signalling at mossy fibre synapses, and potentiated inward currents evoked by local application of l-glutamate onto CA3 pyramidal neurons. It facilitated the induction of mossy fibre LTP, but the magnitude of potentiation was smaller than that observed in untreated slices. The racemic mixture was separated and it was shown that only the (-) enantiomer was active. Toxicity analysis indicated that cell lines tolerated the compound at concentrations well above those enhancing synaptic transmission. Our results unveil a small molecule whose physiological signature resembles that of a potent nootropic drug

Design, 3D printing and validation of a novel low-cost high-capacity sitting-drop bridge for protein crystallization

Sitting drop protein crystallization is not used as commonly as the hanging drop method for crystal optimization due to the limitations of commercially available sitting drop bridges, particularly when they are used in conjunction with 24-well crystallization plates. The commercially available sitting drop bridge, containing space for only a single drop, restricts their wider use. Proteins that preferentially crystallize under sitting-drop conditions therefore require more work, time and resources for their optimization. As a result of these limitations and using 3D-printing, we designed and developed a new sitting drop bridge where five crystallization drops can be placed simultaneously in each well of a 24-well crystallization plate. This significantly simplifies and increases the potential of sitting drops in crystal optimization, reducing costs and hence overcomes existing limitations of current approaches