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Organocatalytic enantioselective desymmetrisation of achiral or meso compounds is a powerful strategy for the construction of enantiomerically enriched complex molecules, often with multiple stereocentres and in high selectivities. Recent years have seen increasing use of organocatalysts in desymmetrisation methodology, in contrast to traditional metal- or enzyme-catalysed reactions, with many impressive advances made in the current decade. This review will provide an overview of the field since 2010, with the aim of highlighting both the practical applications and elegance of enantioselective desymmetrisation to the wider synthetic community.
RESUMO
Controlled covalent attachment of dsDNA horizontally orientated on a gold surface is achieved through the use of a single surface-linker located approximately half way along the attached DNA probe strand. We show that horizontally oriented dsDNA on a gold surface can undergo melting and re-hybridization to target strand in solution and thus can be used for the detection of specific target DNA sequences using surface-enhanced Raman spectroscopy (SERS). We show that a range of lengths of target DNA sequences from â¼30-bases to 78-bases can be specifically hybridized to the short immobilized DNA probe sequence and adopt a horizontal orientation on the gold surface. Following thermal or electrochemically driven melting of the immobilized dsDNA, the target DNA strand diffuses away while the probe strand remains attached to the surface allowing the functionalized surfaces to be reused. The melting of the horizontally orientated immobilized dsDNA can be monitored using SERS either by employing a dye label covalently attached on the DNA target strand or by employing a binding agent selective for dsDNA. This approach of covalently immobilizing the DNA probe strand through a linker located at approximately the middle of the strand has great potential to improve the sensitivity and specificity of molecular assays that employ DNA arrays on solid surfaces.
RESUMO
BACKGROUND: In patients with chronic obstructive pulmonary disease exercise tolerance is commonly limited by breathlessness. These patients have an increased ventilatory load at rest which is exacerbated during exercise. The purpose of this study was to investigate the effect of supporting ventilation by non-invasive inspiratory pressure support (IPS) during submaximal treadmill exercise in such patients to see if they would experience less breathlessness and improve their exercise capacity. METHODS: Eight men with disabling breathlessness due to chronic obstructive pulmonary disease (COPD) (mean (SD) FEV1 0.73 (0.2) 1) were studied. Patients walked on a treadmill until their sensation of breathlessness, scored at one minute intervals, reached level 5 ("severe") on the 10-point Borg scale. Studies were performed with IPS (mean airway pressure 12-15 cm H2O), continuous positive airway pressure (CPAP 6 cm H2O), and with oxygen (2 l/min via a mask) in random order on three separate days. Each of these walks was compared with a control walk using a sham circuit (breathing air via an oxygen mask at 2 l/min from an unlabelled cylinder), and with a baseline walk in which patients walked freely on the treadmill. On cessation of exercise, distance achieved and a leg fatigue score were recorded. RESULTS: No patients stopped due to leg fatigue, all stopping only when their sensation of breathlessness had reached level 5 on the Borg scale. IPS improved median walking distance by 62% compared with the control walk (sham circuit). There was no change in walking distance with either CPAP or oxygen at 2 l/min. There was no difference between the control and the baseline walks. CONCLUSIONS: Inspiratory pressure support can reduce breathlessness and increase exercise tolerance to submaximal treadmill exercise in patients with COPD. This could have implications for the rehabilitation of these severely disabled patients.
