Synthesis of the tricyclic core of alkaloid securinol B using a cascade of vilsmeier-haack and mannich cyclizations

Abstract: The Securinega alkaloids are a family of approximately 20 tetracyclic compounds isolated from diverse Securinega, Phyllanthus, and Margaritaria species of the Euphorbiaceae plant family. Most of these alkaloids possesses an indolizidine skeleton fused with an azabicyclo[3.2.1]octane system, as in securinine (1), the major Securinega alkaloid, and in viroallosecurinine (2) (Figure 1). These compounds exhibit interesting biological activity, such as acting on the central nervous system as γ-aminobutyric acid receptor antagonists. In 1965, Tamura and Iwamoto isolated much rarer hydroxy-substituted Securinega alkaloids, securinol A and B (0.0005% and 0.00009%, respectively), from S. suffriticosa. The structure of these alkaloids was first assigned as 3 and 4. In 1991, Arbain and Sargent identified 5 as the revised structure of securinol A, from X-ray analysis of its crystalline hydrobromide salt. Since both securinol A and B give viroallosecurinine (2) upon treatment with mesyl chloride and pyridine, it was therefore suggested that securinol B has structure 6

Rapid assembly of quinolizidines via consecutive nucleophilic cyclizations onto activated amides

Abstract: A new approach to the synthesis of quinolizidines involving a cascade of nucleophilic cyclizations triggered by chemoselective amide activation is reported. Particular attention was given to the effect of the nature of the tethered nucleophiles on the cascade of cyclizations. As a result, simple acyclic amides gave rapid access to functionalized quinolizidines bearing either a tertiary or quaternary center at the ring junction. Such a fused bicyclic motif is found in several alkaloids

Cyclisations de Vilsmeier-Haack et de Mannich en cascade sur un amide chimiosélectivement activé application à la synthèse totale du («)-sécurinol B

Les travaux de recherches présentés dans cette thèse ont pour but le développement d'une nouvelle stratégie générale de synthèse d'alcaloïdes polycycliques via une cascade de cyclisations de Vilsmeier-Haack et de Mannich impliquant des nucléophiles [pi] carbonés non aromatiques sur un amide chimiosélectivement activé. Au premier chapitre, une étude sur la monocyclisation de Vilsmeier-Haack sera présentée. Dans l'ordre, le développement de conditions d'activation chimiosélectives d'amides en présence de nucléophiles [pi] carbonés non aromatiques, l'étude sur l'étendue de la réaction de monocyclisation ainsi qu'une application à la synthèse de la tashiromine seront abordés. Au deuxième chapitre, une étude sur la cascade de cyclisations de Vilsmeier-Haack et de Mannich impliquant des composés modèles silanes sera illustrée. Une attention particulière sera portée sur l'efficacité de la cyclisation de Mannich en fonction de la nature des nucléophiles entrants en jeux. La cyclisation sur des amides vinylogues activés sera également abordée. Au troisième chapitre, la mise au point d'une séquence synthétique ayant comme étape clé une biscyclisation en cascade sur un formamide activé menant à un intermédiaire avancé dans la synthèse totale du sécurinol B sera exposée. L'influence de la nature du nucléophile de la chaîne latérale sur la cascade de cyclisation sera également discutée. Le chapitre conclura sur les avenues à explorer afin de finaliser le projet

Addition of tethered nonaromatic carbon nucleophiles to chemoselectively activated amides

Abstract: In an effort to develop new ways of synthesizing polycyclic alkaloids, we successfully added silyl enol ethers, allylsilanes, and enamines to iminium ions generated from amides. Because of their higher oxidation state, such iminiums show a yet unexploited advantage of potential double cyclizations over standard Mannich monocyclizations. We report herein the first example of tethered nonaromatic carbon nucleophiles adding to activated amides for the generation of enaminals of various ring sizes, with endo- or exo-cyclic nitrogen

Risk and protective factors for burnout among psychologists and neuropsychologists: A scoping review

Health care professions are emotionally demanding, requiring special skills in caring and empathy. In the health care field, many professions have been linked to burnout, notably through compassion fatigue. Several studies have attempted to determine what factors influence burnout among health care workers in general; however, few have focused exclusively on psychologists (PSYs) and neuropsychologists (NPSYs). This scoping review aims to better understand the determinants of burnout among PSYs and NPSYs specifically. It also aims to identify which factors allow PSYs and NPSYs to adapt and thrive at work despite the difficulties those professions bring. This research focused on burnout, job satisfaction, and well-being at work. Among the most notable results obtained from 27 scientific studies are as follows: (a) PSYs and NPSYs are generally very satisfied at work despite high burnout rates; (b) individual factors and the work environment impact the mental health of PSYs and NPSYs; (c) self-care behaviors are favorable for job satisfaction, and they also decrease the risk of burnout. In addition, it appears that a feeling of autonomy has an important influence on burnout symptoms, which is consistent with self-determination theory. In sum, this scoping review reveals that factors such as self-compassion, work–life balance, control over work, and administrative tasks can reduce the risk of burnout as well as improve job satisfaction and mental health among PSYs and NPSYs

Asymmetric total synthesis of (+)-virosine a via sequential nucleophilic cyclizations onto an activated formamide

Abstract: The first synthesis of tetracyclic alkaloid virosine A is reported. The natural alkaloid was prepared in only 13 steps, in an enantioenriched form. The azabicyclo[2.2.2]octane core was efficiently assembled using a key Vilsmeier–Haack and Mannich cyclizations sequence performed in one pot