Collective Syntheses of Icetexane Natural Products Based on Biogenetic Hypotheses

A divergent synthesis of 10 icetexane natural products based on a proposed biogenetic cationic ring expansion of a reduced carnosic acid derivative is described. Of these icetexanes, (+)-salvicanol, (−)-cyclocoulterone, (−)-coulterone, (−)-obtusinone D, and (−)-obtusinone E have been synthesized for the first time. In addition, the hypothesis for the non-enzymatic biogenesis of benzo[1,3]dioxole natural products has been experimentally investigated. Additional experimental evidence for the abiotic formation of the methylenedioxy unit is provided, as photolysis of the quinone (+)-komaroviquinone resulted in the formation of the [1,3]dioxole-containing natural product (−)-cyclocoulterone and (+)-komarovispirone

AGTEC-Org Agronomy Handbook of Methods

A common handbook was conceived in the CORE Organic AGTEC-Org project in order to give some elements of field trial monitoring

New challenges to improve organic bread wheat production in Europe

The total organic area in the EU-27 had an annual average growth rate of nearly 15% from 1998 to 2006 with winter wheat being the most important cereal crop. Wheat yield in organic farming is around 30% to 70% of yield of conventional farming but higher premia for organic wheat may to some extent compensate for this. Bread wheat is grown in a variety of crop rotations and farming systems and four basic organic crop production systems have been defined. Nitrogen deficiency and weed infestation are considered to be the most serious threat in organic wheat production. Organic wheat producers will have to fulfil the technological needs of bakers although the requirements differ widely from small artisan bakers to large enterprises handling the organic bread processing. To maintain and expand organic wheat production, there is a need to control weed population, manage nitrogen nutrition and maintain crop diversity in the cropping system. In order to obtain a share in the premium price of organic wheat products, farmers may involve in further processing and marketing

Syntheses of taiwaniaquinoid and icetexane natural products based on biogenetic hypotheses

The syntheses of natural products based on biogenetic hypotheses have the potential not only for giving access to short, elegant and efficient synthetic routes, but also to shine light on how nature constructs these breathtaking structures. This work, divided in three experimentally interconnected chapters, will highlight the importance of this approach with the syntheses of taiwaniaquinoid and icetexane natural products. A protecting-group-free route to (−)-taiwaniaquinone F based on a Wolff-rearrangement ring contraction and subsequent aromatic oxidation of a sugiol derivative was deviced following a proposed biogenetic pathway. In addition, the first synthesis of (+)-taiwaniaquinol A is reported via short time exposure of (−)-taiwaniaquinone F to sunlight triggering a remote C−H functionalization. The hypothesis that the biogenesis of several methylenedioxy bridged natural products could proceed via similar nonenzymatic mechanisms is presented. A divergent synthesis of thirteen members of icetexane natural products based on a proposed biogenetic cationic ring expansion of a reduced carnosic acid derivative is described. Among these members, (+)-salvicanol, (−)-cyclocoulterone, (−)-coulterone, (−)-obtusinone D, (−)-obtusinone E, and (−)-euolutchuol E are synthesized for the first time. Following this approach, an additional support to our methylenedioxy biogenetic hypothesis is reported via the photolysis of (+)-komaroviquinone to (−)-cyclocoulterone and (+)-komarovispirone. Preliminary results towards the mechanistic elucidation of the discovered remote C−H activation are outlined. Photolysis of a model substrate shows the formation of the methylenedioxy moiety for the first time on a non-natural quinone. Preliminary evidence that account for the formation of biradical species are given

Syntheses of Taiwaniaquinone F and Taiwaniaquinol A via an Unusual Remote C-H Functionalization

A protecting-group-free route to (-)-taiwaniaquinone F based on a ring contraction and subsequent aromatic oxidation of a sugiol derivative is reported. In addition, the first synthesis of (+)-taiwaniaquinol A is reported via short time exposure of (-)-taiwaniaquinone F to sunlight triggering a remote C-H functionalization. The hypothesis that the biogenesis of some methylenedioxy bridged natural products could proceed via similar nonenzymatic mechanisms is presented

Syntheses of Taiwaniaquinone F and Taiwaniaquinol A via an Unusual Remote C–H Functionalization

A protecting-group-free route to (−)-taiwaniaquinone F based on a ring contraction and subsequent aromatic oxidation of a sugiol derivative is reported. In addition, the first synthesis of (+)-taiwaniaquinol A is reported via short time exposure of (−)-taiwaniaquinone F to sunlight triggering a remote C–H functionalization. The hypothesis that the biogenesis of some methylenedioxy bridged natural products could proceed via similar nonenzymatic mechanisms is presented

Sequential adjustment of cytotoxic T lymphocyte densities improves efficacy in controlling tumor growth

International audienceUnderstanding the human cytotoxic T lymphocyte (CTL) biology is crucial to develop novel strategies aiming at maximizing their lytic capacity against cancer cells. Here we introduce an agent-based model, calibrated on population-scale experimental data that allows quantifying human CTL per capita killing. Our model highlights higher individual CTL killing capacity at lower CTL densities and fits experimental data of human melanoma cell killing. The model allows extending the analysis over prolonged time frames, difficult to investigate experimentally, and reveals that initial high CTL densities hamper efficacy to control melanoma growth. Computational analysis forecasts that sequential addition of fresh CTL cohorts improves tumor growth control. In vivo experimental data, obtained in a mouse melanoma model, confirm this prediction. Taken together, our results unveil the impact that sequential adjustment of cellular densities has on enhancing CTL efficacy over long-term confrontation with tumor cells. In perspective, they can be instrumental to refine CTL-based therapeutic strategies aiming at controlling tumor growth