Calyculins and Related Marine Natural Products as Serine-Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C

Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group. These molecules have become interesting targets for cell biologists and synthetic organic chemists. The serine/threonine protein phosphatases play an essential role in the cellular signalling, metabolism, and cell cycle control. Calyculins express potent protein phosphatase 1 and 2A inhibitory activity, and have therefore become valuable tools for cellular biologists studying intracellular processes and their control by reversible phosphorylation. Calyculins might also play an important role in the development of several diseases such as cancer, neurodegenerative diseases, and type 2-diabetes mellitus. The fascinating structures of calyculins have inspired various groups of synthetic organic chemists to develop total syntheses of the most abundant calyculins A and C. However, with fifteen chiral centres, a cyano-capped tetraene unit, a phosphate-bearing spiroketal, an anti, anti, anti dipropionate segment, an α-chiral oxazole, and a trihydroxylated γ-amino acid, calyculins reach versatility that only few natural products can surpass, and truly challenge modern chemists’ asymmetric synthesis skills

A telecom band single-photon source using a grafted carbon nanotube coupled to a fiber Fabry-Perot cavity in the Purcell regime

We report on the coupling of a reconfigurable high Q fiber micro-cavity to an organic color center grafted to a carbon nanotube for telecom wavelength emission of single photons in the Purcell regime. Using three complementary approaches we assess various figures of merit of this tunable single photon source and of the cavity quantum electrodynamical effects : the brightening of the emitter is obtained by comparison of the count rates of the very same emitter in free-space and cavity coupled regimes. We demonstrate a fiber coupled single-photon output rate up to 20 MHz at 1275~nm. Using time-resolved and saturation measurements, we determine independently the radiative quantum yield and the Purcell factor of the system with values up to 30 for the smallest mode volumes. Finally, we take advantage of the tuning capability of the cavity to measure the spectral profile of the brightness of the source which gives access to the vacuum Rabi splitting $g$ with values up to $25 \; \mu$eV

Copper-catalysed selective hydroamination reactions of alkynes

The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of ​rivastigmine and the formal synthesis of several other pharmaceutical agents, including ​duloxetine, ​atomoxetine, ​fluoxetine and ​tolterodine.National Institutes of Health (U.S.) (GM58160

Synthesis and characterization of new antioxidants, mono-aromatic pulvinic acid derivatives, for dermocosmetic application

Cette thèse a été consacrée à la synthèse de nouveaux dérivés d'acides pulviniques et à l'évaluation de leurs propriétés antioxydantes, pour développer de nouveaux composés à incorporer dans des crèmes à usage dermocosmétique. Les nouveaux composés sont des dérivés dits mono-aromatiques d'acides pulviniques, ne possédant qu un seul noyau aromatique, soit sur la partie sud (produits de type I), soit sur la partie nord (produits de type II). Des voies de synthèse ont été développées et appliquées à la préparation de 45 nouveaux dérivés. L'activité antioxydante de ces composés a été évaluée et comparée aux acides pulviniques classiques. Les tests de protection de la thymidine et d'un plasmide bactérien, ont permis de montrer que les composés de type I étaient aussi actifs que les acides pulviniques classiques, contrairement aux produits de type II, peu actifs. Des tests complémentaires ont montré l'importance de la fonction portée par la double liaison exo-cyclique dans l'activité.This thesis has been devoted to the synthesis of new pulvinic acid derivatives and their antioxydant properties, with the aim to develop new compounds to be incorporated in cosmetic creams. These new compounds are so-called mono-aromatic pulvinic acid derivatives, bearing only one aromatic ring, either on the south side (type I products), or on the north side (type II products). New synthetic routes have been developed and applied for the preparation of 45 new derivatives. Their antioxidant properties have been evaluated and compared to classical pulvinic acids. Protection of thymidine and plasmidic DNA showed that type I compounds were as active as classical pulvinic acids, contrarily to type II products, which are non-active. Complementary tests have shown the crucial role of the functional group on the exo-cyclic double bond

Synthesis and characterization of new antioxidants, mono-aromatic pulvinic acid derivatives, for dermocosmetic application

Cette thèse a été consacrée à la synthèse de nouveaux dérivés d'acides pulviniques et à l'évaluation de leurs propriétés antioxydantes, pour développer de nouveaux composés à incorporer dans des crèmes à usage dermocosmétique. Les nouveaux composés sont dThis thesis has been devoted to the synthesis of new pulvinic acid derivatives and their antioxydant properties, with the aim to develop new compounds to be incorporated in cosmetic creams. These new compounds are so-called mono-aromatic pulvinic acid de