Développement de méthodes de synthèse pour les acides aminés indolizidin-9-ones substitués et utilisation des acides aminés azabicycloalcanes en tant que mimes peptidiques

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Structure-Activity Study of the ORL1 Antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2

The structure-activity requirements of the ORL1 antagonist Ac-Arg-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2 4 were investigated by varying the position, structure, and charge of the Arg residues. Attempts to abridge the peptide by removal of the Arg, D-Cha, and D-p-ClPhe residues abolished affinity for the ORL1 receptor, whereas deletion of the acetamido N-terminus maintained receptor affinity and selectivity. This series of analogues has provided an improved potent and selective ORL1 receptor antagonist, Ac-Cit-D-Cha-Qaa-D-Arg-D-p-ClPhe-NH2.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue

Glasdegib is a recently approved drug for the treatment of acute myeloid leukemia. It is formulated and marketed in monomaleate salt form. In our investigation, we were able to prepare a glasdegib dimaleate form, which could, in theory, exist in double-salt form or as a mixture of salt and co-crystal species. Therefore, the obtained crystals of glasdegib dimaleate were characterized via 15N ssNMR and single-crystal X-ray diffraction, which revealed that the obtained glasdegib dimaleate exists in double-salt form. This is a surprising finding based on the pKa values for glasdegib and maleic acid. Furthermore, we fully characterized the new dimaleate form using thermal analyses (DSC and TGA) and spectroscopy (IR and Raman). Finally, the physicochemical properties, such as solubility and chemical stability, of both forms were determined and compared

Utilisation de la faune invertébrée du sol comme bio-indicateur des effets des polluants

International audienceA critical review of biological parameters used to indicate pollutant impact on soi! quality was conducted. These param eters mention some soi! invertebrates. The value of an indicative organism depends on its life expectancy, life style and specific importance. Nematodes, mites, collembolans, enchytraeids, earthworms, isopods and molluscs are good potential biological indica tors. Biological indicators of bioaccumulation and biological indicators of effects (toxicological and ecological) can be distin guished. Bioaccumulation studies are difficult to interpret, as wide variations could be found, depending on taxonomie group, habitat, organ studied, soi) type or even pollutant type. Sorne groups, such as Collembola, require in depth bioaccumulation studies. It is suggested to use a pool of macro-concentrators, including at least some earthworm, isopod and gastropod species. Toxicological indicators have been well studied and their lethal and sublethal pollutant effects are well known. However, studies have focused on only a few species, such as the earthworm Eiseniafoetida or the collembolan Folsomia candida. These studies should be extended to other zoological groups, as well as to several species from the same group, to generate a representative test battery. Exposure biom arkers and physiological change studies should be emphasised, as they act as very early warning systems of contamination. Data are currently lacking on how soil biological processes malfunction due to pollution. We need to explore the links between pollutant effects on soi! fauna and pollutant effects on soi! functioning. Concerning ecological indicators, studies should develop sampling techniques and parameters, which are specific to ecotoxicological goals. Before-after impact contrai procedures should be carried out, to eliminate the background noise of the study site and only evaluate the influence of pollutants. On the other hand, ecological indices, such as taxonomie diversity or richness, should be used carefully especially concerning chronic pollution. Effects of pollut ants on biological cycle studies seem very promising, but need further information on the life history strategies of many species. Furthermore, the pollutant tolerance of rare species should be considered. The different types of biological indicators yield comple mentary information on pollutant effects. They ail need standard procedures. In this context, studies should be extended and diversi fied, and associate bioaccumulation, toxicological and ecological indicators to provide better information on soi! quality. © 2000 Éditions scientifiques et médicales Elsevier SAS Ecotoxicology / bioindicators of effects / bioaccumulation / soit ecology / soit quality / soit inv ertebrates / soit fauna / earthworms / microarthropods / mites / collembolans / isopods / enchytraeids / snails / soit pollutionUne liste critique des paramètres biologiques utilisés dans certains travaux pour indiquer l'impact des polluants sur la qualité des sols a été établie. Ces paramètres font référence à un ou plusieurs invertébrés du sol. Le rôle d'organisme indicateur dépend de leurs caractéristiques biodémographiques, de leur mode de vie, de leur taille spécifique. Les nématodes, acariens, collemboles, enchytréides, vers de terre, isopodes et gastéropodes sont potentiellement des indicateurs biologiques. Indicateurs biologiques de bioaccumulation et indicateurs biologiques d'effets (toxicologiques et écologiques) peuvent être distingués. Les études de bioaccumulation sont difficiles à interpréter, car de fortes variations sont observées. Ces variations dépendent du groupe taxonomique étudié, de l'habitat, de l'organe étudié, du type de sol ou bien encore du type de pollution. Certains groupes, comme les collemboles demandent des études plus poussées à ce sujet. Il est suggéré d'utiliser un pool de macro-concentrateurs, avec au moins des espèces de vers de terres, isopodes et gastéropodes. Concernant les indicateurs toxicologiques d'effets, les études les plus nombreuses concernent les effets létaux et sublétaux. Toutefois ces études concernent peu de groupes taxonomiques (essentiellement le vers Eisenia foetida et le collembole Folsomia candida), et devraient être étendues à d'autres groupes zoologiques, ainsi qu'à différentes espèces du même groupe, afin de créer une batterie de tests représentatifs. Les travaux concernant les biomarqueurs et les changements physiologiques devraient être amplifiés, car ils permettent d'obtenir des systèmes d'alarme très précoces concernant l'impact des contaminants. Un manque persistant de données concerne les conséquences de pollutions sur le fonctionnement des écosystèmcs. Il est en effet important désormais d'explorer les liens entre les effets des polluants sur la faune du sol et les effets réels de ces mêmes polluants sur le fonctionnement des sols. Concernant les indicateurs écologiques, les travaux entrepris devraient développer des méthodes d'échantillonnage et des paramètres spécifiques au domaine écotoxicologique. Ainsi, il est préconisé d'entreprendre des études combinant les approches synchroniques et diachroniques. afin d'éliminer le bruit de fond induit par le site d'étude et évaluer uniquement l'influence du polluant. En outre, les indices écologiques, comme la diversité ou la richesse taxonomique, doivent être utilisés avec précautions, particulièrement lors des études de pollution chronique. Par ailleurs, les études concernant les effets de polluants sur les cycles biologiques semblent prometteuses, mais demandent de meilleures connaissances concernant les stratégies de vies des différentes espèces étudiées. De plus, la tolérance aux pollutions des espèces rares devrait être fortement prise en considération. Les différents types d'indicateurs biologiques fournissent des informations complémentaires. Ils demandent tous une standardisation des protocoles. Dans ce contexte, les études devraient être développées et diversifiées et associer les indicateurs de bioaccumulation avec les indicateurs biologiques d'effets pour améliorer l'information sur la qualité des sols

A Highly Productive, Whole-Cell DERA Chemoenzymatic Process for Production of Key Lactonized Side-Chain Intermediates in Statin Synthesis

<div><p>Employing DERA (2-deoxyribose-5-phosphate aldolase), we developed the first whole-cell biotransformation process for production of chiral lactol intermediates useful for synthesis of optically pure super-statins such as rosuvastatin and pitavastatin. Herein, we report the development of a fed-batch, high-density fermentation with <i>Escherichia coli</i> BL21 (DE3) overexpressing the native <i>E. coli deoC</i> gene. High activity of this biomass allows direct utilization of the fermentation broth as a whole-cell DERA biocatalyst. We further show a highly productive bioconversion processes with this biocatalyst for conversion of 2-substituted acetaldehydes to the corresponding lactols. The process is evaluated in detail for conversion of acetyloxy-acetaldehyde with the first insight into the dynamics of reaction intermediates, side products and enzyme activity, allowing optimization of the feeding strategy of the aldehyde substrates for improved productivities, yields and purities. The resulting process for production of ((2<i>S</i>,4<i>R</i>)-4,6-dihydroxytetrahydro-2<i>H</i>-pyran-2-yl)methyl acetate (acetyloxymethylene-lactol) has a volumetric productivity exceeding 40 g L⁻¹ h⁻¹ (up to 50 g L⁻¹ h⁻¹) with >80% yield and >80% chromatographic purity with titers reaching 100 g L⁻¹. Stereochemical selectivity of DERA allows excellent enantiomeric purities (<i>ee</i> >99.9%), which were demonstrated on downstream advanced intermediates. The presented process is highly cost effective and environmentally friendly. To our knowledge, this is the first asymmetric aldol condensation process achieved with whole-cell DERA catalysis and it simplifies and extends previously developed DERA-catalyzed approaches based on the isolated enzyme. Finally, applicability of the presented process is demonstrated by efficient preparation of a key lactol precursor, which fits directly into the lactone pathway to optically pure super-statins.</p></div

Procedures and protocol for soil biodiversity monitoring : ‘RMQS-Biodiv', a french pilot area experience.

Poste

Time course of whole-cell, DERA-catalyzed batch reactions.

<p>Reactions were performed using <i>E. coli</i> BL21 (DE3) pET30/<i>deoC</i> fermentation cultures directly (DERA specific activity = 232 kRFU s⁻¹ g⁻¹, WCW = 207 g L⁻¹). Results are given as mass concentrations obtained from GC-FID analysis. The measured quantity of a particular compound, with the exception of the stable 6-ring hemiacetals (<b>3</b>), represents the sum of the corresponding equilibrium forms (hydrate, aldehyde and acetal/hemiacetal), which exist under the reaction conditions. <b>A:</b> Reaction species data from reactions using 400 mmol L⁻¹ of <b>2g</b> and 840 mmol L⁻¹ of <b>1</b> are shown. <b>1</b> (▪, black), <b>3a</b> (▴, blue) <b>3g</b> (♦, green), <b>8g</b> (•, red), <b>10g</b> (Δ, orange) and <b>2g</b> (◊, brown). <b>B:</b> Reaction species data from reactions using 400 mmol L⁻¹ of <b>2b</b> and 840 mmol L⁻¹ of <b>1</b> are shown. <b>1</b> (▪, black), <b>3a</b> (▴, blue) <b>3b</b> (♦, green), <b>8b</b> (•, red), <b>10b</b> (Δ, orange), <b>2b</b> (◊, brown), 2,6-chloro-2,4-dideoxyhexose (□, grey). Concentration of the latter (Information S8) is evaluated based on the assumption, that the GC-FID response factor is similar to that of <b>3b</b>.</p

Procedures and protocol for soil biodiversity monitoring: “RMQS-Biodiv”, a French Pilot area experience

International audienc