Heat in Germany: Health risks and preventive measures

Background: Climate change has already led to a significant temperature increase in Germany. The average temperature in the past decade was approximately 2°C above the pre-industrial level and eight of the ten hottest summers since the beginning of systematic weather records in 1881 were recorded in the last 30 years. Methods: Based on a selective literature search and authors’ evaluations, the article summarises the current state of knowledge on heat and its health impacts for Germany, addresses adaptation measures, and gives an outlook on implementation and research questions. Results: Heat can aggravate pre-existing conditions such as diseases of the cardiovascular system, the respiratory tract, or the kidneys and trigger potentially harmful side effects for numerous medications. A significant increase in mortality is regularly observed during heat events. Previous approaches to mitigate the health impact of high temperatures include, for example, the heat alerts of the German Meteorological Service and recommendations for the preparation of heat-health action plans. Conclusions: Evidence on health impacts of heat and awareness of the need for heat-related health protection have grown in recent years, but there is still a need for further action and research. This is part of a series of articles that constitute the German Status Report on Climate Change and Health 2023

Hitze in Deutschland: Gesundheitliche Risiken und Maßnahmen zur Prävention

Hintergrund: Der Klimawandel hat in Deutschland bereits zu einer deutlichen Temperaturzunahme geführt. So lag die Mitteltemperatur im vergangenen Jahrzehnt rund 2 °C über dem vorindustriellen Niveau und acht der zehn heißesten Sommer seit Beginn der systematischen Wetteraufzeichnungen im Jahr 1881 wurden in den letzten 30 Jahren verzeichnet. Methode: Der Artikel fasst, basierend auf einer selektiven Literaturrecherche und eigenen Auswertungen, den aktuellen Wissensstand zu Hitze und ihren gesundheitlichen Auswirkungen für Deutschland zusammen, geht auf Anpassungsmaßnahmen ein und gibt einen Ausblick auf Umsetzungs- und Forschungsfragen. Ergebnisse: Hitze kann bestehende Beschwerden wie Erkrankungen des Herz-Kreislauf-Systems, der Atemwege oder der Nieren verschlimmern und bei zahlreichen Medikamenten teils schwerwiegende Nebenwirkungen auslösen. Während Hitzeperioden wird regelmäßig ein deutlicher Anstieg der Sterbefälle beobachtet. Bisherige Ansätze zur Abmilderung gesundheitlicher Auswirkungen hoher Temperaturen umfassen z. B. die Hitzewarnungen des Deutschen Wetterdienstes sowie Handlungsempfehlungen für die Erstellung von Hitzeaktionsplänen

Oxidative Cleavage of Ketoximes to Ketones using Photoexcited Nitroarenes

Methoximes are a versatile directing group for a variety of C–H functionalizations. Despite their importance as a powerful functional handle, their conversion to the parent ketone, which is often desired, usually requires harsh and functional group intolerant reaction conditions that make their application in a late-stage context problematic. Here, we present an alternative set of conditions to achieve mild and functional group tolerant conversion of methoximes to the parent ketones using photoexcited nitroarenes. The utility of this methodology is showcased in its application in the total synthesis of cephanolide D. Furthermore, mechanistic insight into this transformation obtained using isotope labeling studies as well as the analysis of reaction byproducts is provided

Oxidative cleavage of ketoximes to ketones using photoexcited nitroarenes.

The methoxime group has emerged as a versatile directing group for a variety of C-H functionalizations. Despite its importance as a powerful functional handle, conversion of methoximes to the parent ketone, which is often desired, usually requires harsh and functional group intolerant reaction conditions. Therefore, the application of methoximes and their subsequent conversion to the corresponding ketone in a late-stage context can be problematic. Here, we present an alternative set of conditions to achieve mild and functional group tolerant conversion of methoximes to the parent ketones using photoexcited nitroarenes. The utility of this methodology is showcased in its application in the total synthesis of cephanolide D. Furthermore, mechanistic insight into this transformation obtained using isotope labeling studies as well as the analysis of reaction byproducts is provided

Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide.

Skeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners - representing the reverse of the proposed biosynthesis (i.e., a contra-biosynthesis approach). Computational evaluation of our designed transformation prompted us to investigate a Büchner-Curtius-Schlotterbeck reaction of a p-quinol methylether, which ultimately results in the synthesis of harringtonolide in two steps from cephanolide A, which we had previously prepared. Additional computational studies reveal that unconventional selectivity outcomes are driven by the choice of a Lewis acid and the nucleophile, which should inform further developments of these types of reactions

A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines

A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium­(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetra­hydro­isoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxy­erythratidinone

The Aryne Phosphate Reaction

Condensed phosphates are a critically important class of molecules in biochemistry, with a myriad of derived structures being known. Moreover, non-natural analogues are important for various applications, such as single molecule real time DNA sequencing. Often, such analogues contain more than three phosphate units in their oligophosphate chain. Consequently, investigations into phosphate reactivity enabling new ways of phosphate functionalization and oligophosphorylation are an essential endeavour in the field. Here, we scrutinize the potential of phosphates to act as arynophiles, paving the way for follow-up oligophosphorylation reactions. The aryne phosphate reaction is a powerful tool to – depending on the perspective – (oligo)phosphorylate arenes or arylate (oligo-cyclo)phosphates. Based on Kobayashi-type o-silylaryltriflates, the aryne phosphate reaction enables rapid entry into a broad spectrum of arylated products, like monophosphates, diphosphates, phosphodiesters and polyphosphates. The synthetic potential of these new transformations is demonstrated by efficient syntheses of nucleotide analogues and an unprecedented one-flask octaphosphorylation