New methodology for the synthesis of chiral, non-racemic a-tertiary amine centres: application to the synthesis of the marine alkaloid lepadiformine

The development of new methodology for the synthesis of a chiral, non-racemic quaternary carbon bearing an α-nitrogen (an α-tertiary amine or ATA) continues to be an active area of modern research in current synthetic organic chemistry. As a privileged biological scaffold, ATAs are widespread amongst bioactive natural products, providing an inspiration in their complex architecture to synthetic chemists in drug discovery programmes. Three experimental endeavours comprise this project, which are presented as separate sections of Chapter 2. The first part focuses on new methodology for all-carbon quaternization based on an auxiliary-based diastereoselective alkylation of an auxiliary-malonate, in which an imidazolidinone auxiliary provided excellent facial selectivities in the alkylation in conjunction with KHMDS as the base. Five derivatives were generated in high yields (>85 %) and selectivities (dr >95:5). Extension of the methodology to generate ATAs using the auxiliary-malonate system forms the basis of the second section. This was achieved via a modified Curtius rearrangement protocol performed on quaternary carboxylic acids, in turn obtained from a chemoselective cleavage of a PMB ester malonate-auxiliary system. The ATA products were obtained in high yields and with retention of stereoselectivity, and following the non-destructive removal of the auxiliary by methanolysis, produced enantioenriched α,α-disubstituted alanine and phenylalanine methyl esters. Additional steps on other suitable derivatives furnished α-quaternary proline and lysine derivatives, all in high ees (96 – 98 %). The methodology offers a general approach to the production of enantioenriched ATAs, and in particular, access to both natural and unnatural α,α-disubstituted amino acids. Application to an attempted synthesis of lepadiformine is described in the final section, whereby the ATA of the alkaloid is constructed in an acyclic form employing the newly developed methodology. Reductive (non-destructive) removal of the auxiliary provided an amino alcohol derivative that was further elaborated via a sequence involving ring-closing metathesis, hydrogenation, hydroxyl group oxidation and Grignard addition to afford a functionalised A-ring of lepadiformine A, with key functionality in place for elaboration to the target. However, dehydration of the tertiary alcohol from the Grignard step, although successful in a related model study, led to problems, bringing the total synthesis endeavour to a close. In spite of this setback, the divergent nature of the approach allows for new designs in the synthetic plan, particularly regarding the order of which the functionalised A ring from this work is elaborated into the A/B/C target

Future cooling gap in the Shared Socioeconomic Pathways

Lack of access to cooling is and will become an even more prominent challenge to climate change adaptation as heat stress continues to rise. Here we analyze the socio-economic dimensions of adaptive capacity to deal with heat stress, and find that income, urbanization and inequality are factors that correlate with adaptation against heat stress. Using the scenario space of the Shared Socioeconomic Pathways, we estimate future trajectories of the cooling gap, which measures the difference between the population exposed to heat stress and population with access to a cooling device. Depending on the scenario, total population affected by the cooling gap could vary between 3.7 to 1.4 billion people in 2050, and between 0.1 and 4.8 billion at the end of the century. Our analysis shows vast regional inequalities in the capacity to adapt to one of the most common manifestations of climate change and underscores the need for considering the temporal evolution of adaptive capacity in assessments of climate change impacts

Governance in socioeconomic pathways and its role for future adaptive capacity

Governance is one of the critical components for sustainability, but quantification within scenarios and projections of future socioeconomic development has been lacking. This analysis of various pathways looks at how best to overcome 'weak' governance and strengthen adaptive capacity. Weak governance is one of the key obstacles for sustainable development. Undoubtedly, improvement of governance comes with a broad range of co-benefits, including countries' abilities to respond to pressing global challenges such as climate change. However, beyond the qualitative acknowledgement of its importance, quantifications of future pathways of governance are still lacking. This study provides projections of future governance in line with the Shared Socioeconomic Pathways. We find that under a 'rocky road' scenario, 30% of the global population would still live in countries characterized by weak governance in 2050, while under a 'green road' scenario, weak governance would be almost entirely overcome over the same time frame. On the basis of pathways for governance, we estimate the adaptive capacity of countries to climate change. Limits to adaptive capacity exist even under optimistic pathways beyond mid-century. Our findings underscore the importance of accounting for governance in assessments of climate change impacts

Why Ambitious and Just Climate Mitigation Needs Political Science

A large-scale transformation of the energy system, which climate mitigation entails, is a global and highly politicized problem. This thematic issue brings together scholars who work with Integrated Assessment Models (IAMs)—which are used for Intergovernmental Panel on Climate Change (IPCC) reports and other key analyses of future climate trajectories—and social scientists working on climate and energy issues to highlight how the two strands of research could benefit from combining insights across different disciplines and methods. One of the key messages across almost all contributions is that the more technical perspectives could benefit from adjusting their assumptions to reflect the patterns observed in quantitative and qualitative social science. Combining different disciplines is methodologically challenging but promising to ensure that the mitigation strategies developed are considered technically and politically feasible, as well as just

Adaptation constraints in scenarios of socio-economic development

The article processing charge was funded by the Open Access Publication Fund of Humboldt-Universität zu Berlin.Climate change adaptation is paramount, but increasing evidence suggests that adaptation action is subject to a range of constraints. For a realistic assessment of future adaptation prospects, it is crucial to understand the timescales needed to overcome these constraints. Here, we combine data on documented adaptation from the Global Adaptation Mapping Initiative with national macro indicators and assess future changes in adaptation constraints alongside the Shared Socioeconomic Pathways, spanning a wide range of future socio-economic development scenarios. We find that even in the most optimistic scenario, it will take until well after 2050 to overcome key constraints, which will limit adaptation for decades to come particularly in vulnerable countries. The persistence of adaptation constraints calls for stringent mitigation, improved adaptation along with dedicated finance and increasing efforts to address loss and damage. Our approach allows to ground truth indicators that can be further used in climate modelling efforts, improving the representation of adaptation and its risk reduction potential.Peer Reviewe

The microeconomics of adaptation: Evidence from smallholders in Ethiopia and Niger

Climate change is expected to bring higher temperatures, changes to rainfall patterns and in many places increased frequency and severity of extreme weather. Climate change is slated to affect the global food equation both on the supply and demand side as well as local level food systems where small farm communities often depend on local and their own production. As climate change has become more pronounced, the risk to land-based food security faced by many of the world's poor, such as rural communities in Ethiopia and Niger, seems to have become more intense and less predictable. To avoid food insecurity in response to climatic and other stressors, adaptation by small-scale, subsistence farms needs to be accelerated. To effectively intervene to do so, there is a need to understand adaptive behavior in terms of its drivers and its relation with welfare outcomes such as food security. In this paper, we develop a conceptual framework of risk and adaptation, use regression and cluster analysis and the most recent version of the Living Standards Measurement Surveys data for rural areas in Ethiopia and Niger, to advance our understanding. We find that adaptation is associated with lower food insecurity in Ethiopia but not in Niger. Formal education appears as a central element of adaptive capacity and is associated with both adaptive production and income strategies. Female-headed households are much less adapted to a changing climate. Perceived risk based on past hazard experience is crucial for adaptation. Results from the cluster analysis confirm that spatial poverty traps exist. To maintain or enhance welfare in the short term and resilience in the long run in the face of a changing climate, policy makers would do well to focus on micro-regions identified as highly food insecure and build adaptive capacity through, for example, gender inclusive education interventions

The microeconomics of adaptation: Evidence from smallholders in Ethiopia and Niger

Climate change is expected to bring higher temperatures, changes to rainfall patterns and in many places increased frequency and severity of extreme weather. Climate change is slated to affect the global food equation both on the supply and demand side as well as local level food systems where small farm communities often depend on local and their own production. As climate change has become more pronounced, the risk to land-based food security faced by many of the world's poor, such as rural communities in Ethiopia and Niger, seems to have become more intense and less predictable. To avoid food insecurity in response to climatic and other stressors, adaptation by small-scale, subsistence farms needs to be accelerated. To effectively intervene to do so, there is a need to understand adaptive behavior in terms of its drivers and its relation with welfare outcomes such as food security. In this paper, we develop a conceptual framework of risk and adaptation, use regression and cluster analysis and the most recent version of the Living Standards Measurement Surveys data for rural areas in Ethiopia and Niger, to advance our understanding. We find that adaptation is associated with lower food insecurity in Ethiopia but not in Niger. Formal education appears as a central element of adaptive capacity and is associated with both adaptive production and income strategies. Female-headed households are much less adapted to a changing climate. Perceived risk based on past hazard experience is crucial for adaptation. Results from the cluster analysis confirm that spatial poverty traps exist. To maintain or enhance welfare in the short term and resilience in the long run in the face of a changing climate, policy makers would do well to focus on micro-regions identified as highly food insecure and build adaptive capacity through, for example, gender inclusive education interventions

Accounting for socioeconomic constraints in sustainable irrigation expansion assessments

Sustainable irrigation expansion over water limited croplands is an important measure to enhance agricultural yields and increase the resilience of crop production to global warming. While existing global assessments of irrigation expansion mainly illustrate the biophysical potential for irrigation, socioeconomic factors such as weak governance or low income, that demonstrably impede the successful implementation of sustainable irrigation, remain largely underexplored. Here we provide five scenarios of sustainable irrigation deployment in the 21st century integrated into the framework of Shared Socioeconomic Pathways, which account for biophysical irrigation limits and socioeconomic constraints. We find that the potential for sustainable irrigation expansion implied by biophysical limits alone is considerably reduced when socioeconomic factors are considered. Even under an optimistic scenario of socio-economic development, we find that additional calories produced via sustainable irrigation by 2100 might reach only half of the maximum biophysical potential. Regions with currently modest socioeconomic development such as Sub-Saharan Africa are found to have the highest potential for improvements. In a scenario of sustainable development, Sub-Saharan Africa would be able to almost double irrigated food production and feed an additional 70 million people compared to 2020, whereas in a scenario where regional rivalry prevails, this potential would be halved. Increasing sustainable irrigation will be key for countries to meet the projected food demands, tackle malnutrition and rural poverty in the context of increasing impacts of anthropogenic climate change on food systems. Our results suggest that improving governance levels for example through enhancing the effectiveness of institutions will constitute an important leverage to increase adaptive capacity in the agricultural sector.Bundesministerium für Bildung und Forschunghttp://dx.doi.org/10.13039/501100002347H2020Peer Reviewe

Future cooling gap in shared socioeconomic pathways

The extent to which societies will globally be able to adapt to climate change is not well understood. Here we analyze socioeconomic dimensions of adaptive capacity of populations to deal with heat stress and find income, urbanization and income inequality to be important factors in explaining adaptation to heat stress with air conditioning (AC). Using the scenario framework of the Shared Socioeconomic Pathways (SSPs), we estimate the future cooling gap, which represents the difference between the population exposed to heat stress and the population able to protect against heat stress with AC. Depending on the scenario of socioeconomic development, total population affected by the cooling gap may vary between 2 billion and 5 billion people in 2050, with the scenario-dependent range widening further towards the end of the century. Our analysis shows vast regional inequalities in adaptive capacity for one of the most universal manifestations of climate change, underscoring the need to account for the different potential levels of adaptive capacity in assessments of climate change impacts

Sudden Bilateral Choroidal Detachment in a Patient with Posterior Reversible Encephalopathy Syndrome

BACKGROUND: Pre-eclampsia is one of the most important causes of a rare cliniconeuroradiological entity called posterior reversible encephalopathy syndrome. The syndrome is characterized by headacke, visual disturbances, seizures, altered mental status and radiological findings of edema in the white matter of the brain areas perfused by the posterior brain circulation.CASE REPORT: Here we present a patient with sudden bilateral visual loss and deafness in early postnatal period without any other neurological deficits, but with affiliated ophthalmological pathology. The correct diagnosis was made 3 days after the Cesarean section.The patient was diagnosed with posterior reversible encephalopathy syndrome and bilateral choroidal detachment.CONCLUSION: Vascular changes in posterior reversible encephalopathy syndrome can cause visual disturbances not only by brain edema, but combined brain and ocular pathology