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A useful protocol for achieving decarboxylative cross-coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag–Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form, coupling partners can be combined i
A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans-6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji–Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite dia
Erythrina alkaloids represent a rich source of complex polycyclic, bioactive natural products. In addition to their sedative and hypotensive effect, their curare-like activity and structural framework have made them attractive targets for synthetic and medicinal chemists. (+)-Dihydro-β-erythroidine (DHβE), the most potent nicotine acetylcholine receptor antagonist (nAChR) of the Erythrina fam
Abstract There is a pressing need, particularly in the field of drug discovery, for general methods that will enable direct coupling of tertiary alkyl fragments to (hetero)aryl halides. Herein a uniquely powerful and simple set of conditions for achieving this transformation with unparalleled generality and chemoselectivity is disclosed. This new protocol is placed in context with other recently rThere is a pressing need, particularly in the field of drug discovery, for general methods that will enable direct coupling of tertiary alkyl fragments to (hetero)aryl halides. Herein a uniquely powerful and simple set of conditions for achieving this transformation with unparalleled generality and chemoselectivity is disclosed. This new protocol is placed in context with other recently repor
This paper describes the development of a new variant of stereoselective strain-release driven reactions (formal homo [3 + 2] dipolar cycloadditions) which utilize housane (1) to construct functionalized amino alcohols and pyridine-substituted cyclopentanes in two to three steps from simple and easily available building blocks (nitrones and pyridine N-oxides respectively).
Refractory acute myeloblastic leukemia (AML) is poorly studied. In this study, we characterized primary refractory AML and investigated treatment and outcome in a population-based setting. Based on all AML patients receiving intensive induction therapy at 12 Swedish hospitals from 2011 to 2018 (N = 1221), we identified 306 patients that failed to achieve composite complete remission (CRc) after fi
Purpose: In a multicenter prospective cohort study, we assessed the diagnostic yield of the Nordic guidelines for germline investigation in myeloid neoplasms and mapped the spectrum of inherited and somatic variants. Experimental Design: Eighty-five patients (acute myeloid leukemia, n = 38; myelodysplastic syndromes, n = 26; thrombocytopenia, n = 14; and other, n = 7) fulfilling the Nordic criteri
Abstract Herein we report on the decarboxylative alkenylation between alkyl carboxylic acids and enol triflates. The reaction is mediated by a dual catalytic nickel and iridium system, operating under visible light irradiation. Two competing catalytic pathways, from the excited state iridium photocatalyst, are identified. One is energy transfer from the excited state, resulting in formation of an
Phase field crystal (PFC) modeling is employed to investigate the migration dynamics of FCC and BCC symmetric tilt grain boundaries (GBs) under an applied artificial driving pressure. The evolution of GB position, velocity, mobility, structure and energy is tracked to explore the interdependencies of these quantities. The use of PFC permits simulations with atom scale spatial resolution over exten
Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at β2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and
Abstract 4-Alkenyl- and 4-acyloxazoles represent important substructures across a diverse array of bioactive molecules. Practical methods to synthesize these motifs are, therefore, of considerable interest. Here, we develop a novel domino process wherein a cycloisomerization is followed by a 1,2-rearrangement via an oxazolonium ion to yield 4-alkenyloxazoles from an abundant β-chloro-N-benzyl prop4-Alkenyl- and 4-acyloxazoles represent important substructures across a diverse array of bioactive molecules. Practical methods to synthesize these motifs are, therefore, of considerable interest. Here, we develop a novel domino process wherein a cycloisomerization is followed by a 1,2-rearrangement via an oxazolonium ion to yield 4-alkenyloxazoles from an abundant β-chloro-N-benzyl propargylamin
Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) - one of the most prominent members of thi
This article describes practitioners’ motivations to work with daylighting and their educational needs, explored through the Goal Framing Theory (GFT) lens. The study is based on the results of 14 focus groups with 64 daylight experts from Denmark, Italy, Poland, and Sweden. The results, analysed through the GFT, revealed that experts’ motivations were driven by normative, hedonic, and gain goals
OBJECTIVE: To qualitatively explore the perceptions of Para athletes, coaches and stakeholders of the implementation, use and effects of the health promotion intervention 'Safe and Healthy Para sport' (SHAPE). A secondary aim was to explore participants' perceptions of how safety and health in Para sport could be further developed.METHODS: As part of a process evaluation, this qualitative, descrip
Framväxten och övergången till en alltmer kunskapsbaserad ekonomi har de senaste decennierna omformat grunderna för arbete, möjligheter och politiska attityder i de flesta avancerade ekonomier. Mycket av den offentliga och akademiska debatten har i detta sammanhang betonat ökande regionala klyftor, växande ojämlikheter, ökad osäkerhet, minskad social rörlighet och i kölvattnet av detta också ett vThe transformation to the knowledge economy has reshaped the foundations of work, opportunity, and political sentiment across advanced democracies. Much of the public and academic debate has emphasized deepening regional divides, increasing inequalities, growing precarity, the erosion of upward mobility, and growing social discontent.This PhD thesis explores the geographies of low-income work in S
Scholar-activism—academic scholars engaging in some form of activism—has recently become a prominent phenomenon as we witness calls for scholars to engage in political, social, and environmental causes that go beyond their traditional academic duties. An emerging literature focuses on scholar-activism as an object of study. However, the literature is scattered across rather disconnected discipline
