Dermocanarin 1

Background: Enhancing cardiovascular fitness can lead to substantial health benefits. High-intensity interval training (HIT) is an efficient way to develop cardiovascular fitness, yet comparisons between this type of training and traditional endurance training are equivocal. Objective: Our objective was to meta-analyse the effects of endurance training and HIT on the maximal oxygen consumption (VO2max) of healthy, young to middle-aged adults. Methods: Six electronic databases were searched (MEDLINE, PubMed, SPORTDiscus, Web of Science, CINAHL and Google Scholar) for original research articles. A search was conducted and search terms included 'high intensity', 'HIT', 'sprint interval training', 'endurance training', 'peak oxygen uptake', and 'VO2max'. Inclusion criteria were controlled trials, healthy adults aged 18-45 years, training duration ≥2 weeks, VO2max assessed pre- and post-training. Twenty-eight studies met the inclusion criteria and were included in the meta-analysis. This resulted in 723 participants with a mean ± standard deviation (SD) age and initial fitness of 25.1 ± 5 years and 40.8 ± 7.9 mL·kg(-1)·min(-1), respectively. We made probabilistic magnitude-based inferences for meta-analysed effects based on standardised thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject SDs for baseline VO2max. Results: The meta-analysed effect of endurance training on VO2max was a possibly large beneficial effect (4.9 mL·kg(-1)·min(-1); 95 % confidence limits ±1.4 mL·kg(-1)·min(-1)), when compared with no-exercise controls. A possibly moderate additional increase was observed for typically younger subjects (2.4 mL·kg(-1)·min(-1); ±2.1 mL·kg(-1)·min(-1)) and interventions of longer duration (2.2 mL·kg(-1)·min(-1); ±3.0 mL·kg(-1)·min(-1)), and a small additional improvement for subjects with lower baseline fitness (1.4 mL·kg(-1)·min(-1); ±2.0 mL·kg(-1)·min(-1)). When compared with no-exercise controls, there was likely a large beneficial effect of HIT (5.5 mL·kg(-1)·min(-1); ±1.2 mL·kg(-1)·min(-1)), with a likely moderate greater additional increase for subjects with lower baseline fitness (3.2 mL·kg(-1)·min(-1); ±1.9 mL·kg(-1)·min(-1)) and interventions of longer duration (3.0 mL·kg(-1)·min(-1); ±1.9 mL·kg(-1)·min(-1)), and a small lesser effect for typically longer HIT repetitions (-1.8 mL·kg(-1)·min(-1); ±2.7 mL·kg(-1)·min(-1)). The modifying effects of age (0.8 mL·kg(-1)·min(-1); ±2.1 mL·kg(-1)·min(-1)) and work/rest ratio (0.5 mL·kg(-1)·min(-1); ±1.6 mL·kg(-1)·min(-1)) were unclear. When compared with endurance training, there was a possibly small beneficial effect for HIT (1.2 mL·kg(-1)·min(-1); ±0.9 mL·kg(-1)·min(-1)) with small additional improvements for typically longer HIT repetitions (2.2 mL·kg(-1)·min(-1); ±2.1 mL·kg(-1)·min(-1)), older subjects (1.8 mL·kg(-1)·min(-1); ±1.7 mL·kg(-1)·min(-1)), interventions of longer duration (1.7 mL·kg(-1)·min(-1); ±1.7 mL·kg(-1)·min(-1)), greater work/rest ratio (1.6 mL·kg(-1)·min(-1); ±1.5 mL·kg(-1)·min(-1)) and lower baseline fitness (0.8 mL·kg(-1)·min(-1); ±1.3 mL·kg(-1)·min(-1)). Conclusion: Endurance training and HIT both elicit large improvements in the VO2max of healthy, young to middle-aged adults, with the gains in VO2max being greater following HIT when compared with endurance training.

Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of para-substituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.

Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to the facile decomposition of BCP cations, which has severely limited the applications of this strategy. Herein, we report the electrophilic activation of [1.1.1]propellane in a halogen bond complex, which enables its reaction with electron-neutral nucleophiles such as anilines and azoles to give nitrogen-substituted BCPs that are prominent motifs in drug discovery. A detailed computational analysis indicates that the key halogen bonding interaction promotes nucleophilic attack without sacrificing cage stabilisation. Overall, our work rehabilitates electrophilic activation of [1.1.1]propellane as a valuable strategy for accessing functionalised BCPs.