Chimiste | EPFL Graph Search

Un chimiste est un scientifique qui étudie la chimie, c’est-à-dire la science de la matière à l’échelle moléculaire ou atomique (« supra-atomique »). Le mot chimiste est dérivé d’alchimiste mais prend un sens bien différent. Si l’on considère les alchimistes pré-scientifiques, on peut dire que la profession de chimie constitue l’une des plus anciennes professions scientifiques de l’Histoire. Plusieurs des avancées en chimie furent effectuées par des pharmaciens, des biologistes ou des physiciens, les sciences de la nature étudiant les mêmes objets selon des points de vue et des méthodes différentes (Marie Curie, Niels Bohr et Linus Pauling) Histoire Tappūtī-Bēlet-ekalle est parfois considérée comme l'une des premières femmes chimistes dont le nom soit connu dans l'histoire. Elle était une est parfumeuse (muraqqītu) de la cour d'Assyrie dans la seconde moitié du , Rôle des chimistes vignette|Marie Curie, prix Nobel de chimie en 1911 pour sa découverte du rad

Synthetic Studies on Daphmanidin C and Maytenone Based on Biosynthetic Considerations and Natural Product Hybrids as Tools for Quorum Sensing

Adrien Keith Lawrence

The isolation and characterisation of natural products remains a challenge in chemistry owing to nature's magnificent diversity. Natural products or natural product derivatives have always been used in traditional medicine to treat a variety of diseases. To date, these compounds or their derivatives represent 40-60 % of total drugs found on the market. Hence, they provide key leads and structural inspiration in the search for next generation therapeutic drugs. This thesis is divided in two parts and comprises three research projects, which are presented in Chapter 2, 3 and 4. Each chapter presents the synthesis of three types of natural products that could be used as potential therapeutic agents. Each chapter includes an introduction, an overview of previous contributions in the field, a detailed account of our work and a conclusion. Experimental procedures and references are reported at the end of each chapter for convenience. After the presentation of the general conclusion in Chapter 5, spectroscopic data is available. The first part of this thesis documents the synthetic efforts towards daphmanidin C and maytenone, two natural products with interesting biological properties. Daphmanidin C is an Daphniphyllum alkaloid which displayed promising results for the treatment of neurodegenerative diseases during biological testings. Chapter 2 describes the synthesis of the three fragments into which this molecule was divided. The synthetic strategy was then studied on a model system and shown to be relevant. Chapter 3 presents an improved synthetic sequence towards ferruginol, postulated precursor of maytenone and iso-maytenone, two bis-homoditerpenes possessing a complex skeleton which has challenged chemists since the 1960s. Studies of the oxidative biomimetic dimerisation of ferruginol are discussed and an outlook on a potential new strategy to address the synthesis of these dimers is proposed. Part II presents a novel approach to the field of quorum sensing which involves the use of natural product hybrids. Natural product hybrids result from the fusion of two or more fragments of natural products while retaining the biological function of each entity. Chapter 4 describes the design and the synthesis of hybrids which may interact with quorum sensing pathways. These hybrids may be used for surface functionalisation, as molecular probes in chemical biology or as potential antibacterial agents. The General Conclusion (Chapter 5) synthesis the achievements of the two main parts of this thesis.

EPFL2010

New access to long-chain polyketides and spiroketals by umpolung of electron rich dienes with sulfur dioxide

Freddy Fonquerne

Natural polyketides show important biological activity. The inherent stereochemical complexity present in this class of molecules has captured the imagination of organic chemists. Their stereocontrolled, asymmetric total synthesis is a permanent and stimulating area of research. Previous efforts in our group demonstrated that the Umpolung of electron rich 1,3-dienes with SO2 could represent an efficient synthetic strategy to polyketides. Under appropriate conditions sulfur dioxide reacts with 1,3-dienes in the hetero-Diels-Alder fashion. In the case of 1-alkoxy-1,3-dienes, the 6-alkoxy-3,6-dihydro-1,2-oxatiin-2-oxides (sultines) so-obtained can be ionized in the presence of a Lewis or protic acid. The resulting zwitterionic intermediates can be trapped with enoxysilanes (oxyallylation) to generate the corresponding substituted alkenylsulfinates. Desilylation of the latter under acidic conditions leads to allylsulfinic acid intermediates, which, after retro-ene desulfitation, produce 4-alkoxyhepta-6-en-2-one core, a valuable fragment in polyketide natural product synthesis. This new SO2 cascade reaction, hetero-Diels-Alder addition/oxyallylation/retro-ene desulfitation (Vogel's cascade) has been extended to 1-alkoxy-3-acyloxy-1,3-pentadienes. Their use in this cascade reaction allowed the generation of 1,3-polyols array containing keto and enol ester functions, suitable for further chain elongation. In addition, this work highlights the extension of this methodology to other types of p-nucleophiles. The use of carefully elaborated allylsilanes allowed the preparation in a single operation (one pot double oxyallylation reaction) of long chain polyketides of 13 carbons units. Finally, a new route to the spiroketals A/B and C/D and of Spongistatins is presented in order to demonstrate the utility and the versatility of this approach.

EPFL2005

Using collective knowledge to assign oxidation states of metal cations in metal-organic frameworks

Kevin Maik Jablonka, Seyedmohamad Moosavi, Daniele Ongari, Berend Smit

Knowledge of the oxidation state of metal centres in compounds and materials helps in the understanding of their chemical bonding and properties. Chemists have developed theories to predict oxidation states based on electron-counting rules, but these can fail to describe oxidation states in extended crystalline systems such as metal-organic frameworks. Here we propose the use of a machine-learning model, trained on assignments by chemists encoded in the chemical names in the Cambridge Structural Database, to automatically assign oxidation states to the metal ions in metal-organic frameworks. In our approach, only the immediate local environment around a metal centre is considered. We show that the strategy is robust to experimental uncertainties such as incorrect protonation, unbound solvents or changes in bond length. This method gives good accuracy and we show that it can be used to detect incorrect assignments in the Cambridge Structural Database, illustrating how collective knowledge can be captured by machine learning and converted into a useful tool.

NATURE RESEARCH2021

Synthetic Studies on Daphmanidin C and Maytenone Based on Biosynthetic Considerations and Natural Product Hybrids as Tools for Quorum Sensing

Adrien Keith Lawrence

EPFL2010