Bicatalytic Multistep Reactions En Route to the One-Pot Total Synthesis of Complex Molecules: Easy Access to Chromene and 1,2-Dihydroquinoline Derivatives from Simple Substrates

By combining nanocatalysis and base-catalysis, a novel one-pot multistep process was found for the synthesis of substituted heterocycles of biological relevance from simple substrates. It is based on an initial Au/O2 oxidation of allylic alcohols followed by a base-catalysed tandem hetero-Michael/aldolisation/crotonisation with ortho-hydroxy or ortho-amino benzaldehydes. The flexibility of the reaction even allowed the benzaldehyde partner to be prepared in situ in an example of one-pot/5-steps process

Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells

Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

Catalytic tandem reactions triggered by the introduction of a carbonyl function.

International audienc

Oxydation d'époxydes en a-dicetones catalysée par des dérives du bismuth (applications en chimie fine)

L'étude des propriétés du bismuth dans le domaine de l'oxydation de substrats organiques a abouti à la mise au point de nouveaux systèmes oxydants catalytiques. Les travaux principaux ont porté sur la description d'une nouvelle transformation permettant l'oxydation directe d'un époxyde en son dérivé a-dicétone. L'originalité du processus réside dans le mode d'introduction des réactifs sous forme de précurseurs du catalyseur qui sera généré in situ à partir de bismuth métallique et d'additifs. Une étude expérimentale et théorique de la réaction a permis d'aboutir une meilleure compréhension du mécanisme avec une proposition de cycle catalytique. Ce travail a donné lieu à plusieurs applications intéressantes dans le domaine de la chimie fine. Un nouvel accès à plusieurs a-dicétones utilisées dans le domaine de la chimie des arômes a été proposé. Une synthèse originale d'hétérocycles azotés insaturés, les quinoxalines, a été mise au point par une stratégie de couplage oxydant époxydeßène-1,2-diamine.The properties of bismuth compounds in the oxidation of organic substrates have been studied and led to new catalytic oxidative systems. The main topic of this work was directed toward a new transformation involving the direct oxidation of epoxides to a-diketones. An interesting feature of this process is the in situ generation of the catalyst from metallic bismuth and additives. An experimental and theoretical study led to some mechanistic insights with a proposed catalytic cycle. This work has found some applications in fine chemistry. A novel access to various flavouring a-diketones has been proposed. A new synthesis of quinoxaline rings has been described involving the oxidative coupling of epoxides and ene-1,2-diamines.NICE-BU Sciences (060882101) / SudocSudocFranceF

Enzyme-Catalysed Conversion of Atranol and Derivatives into Dimeric Hydrosoluble Materials: Application to the Preparation of a Low-Atranol Oakmoss Absolute

Oakmoss absolute, a solvent extract from Evernia prunastri, is a valuable fragrance ingredient widely used in fine fragrance for almost two centuries. Some minor components of oakmoss absolute, such as atranol and chloroatranol, are attested contact allergens and their presence in fragrance and cosmetic products should be as low as possible. In this context, we have developed an enzyme-based protocol upon which these undesirable molecules are converted in a hydrosoluble dimeric material, and thus easily separated from the absolute by liquid⁻liquid extraction. Analytical and sensory analyses were performed to confirm the specificity of the process, the absence of alteration of the olfactory quality of the absolute, and the final titles of atranol and chloroatranol, which eventually were observed in the ppm range. This highly sustainable process is a viable alternative to conventional time-, energy-, and manpower-consuming techniques to produce very low-atranol oakmoss absolute

Unusual Polycyclic Fused Product by Oxidative Enzymatic Dimerisation of 5-methylpyrogallol Catalysed by Horseradish Peroxidase/H2O2

During investigations on the peroxidase-catalysed oxidation of polyhydroxylated monoaromatic substrates such as 5-methylpyrogallol, we observed a spectacular dimerisation proceeding by dearomatisation in contrast with most common reaction patterns involving phenolics oxidation and dimerization. A tetracyclic fused product featuring an unusual 2-oxatetracyclo [6.3.1.01,6.04,12] dodecan-3-one core was obtained and characterized by combined NMR techniques and high resolution mass spectroscopy (HRMS). This is an example of a spontaneous cascade triggered by a simple enzymatic reaction that could provide new options for biosynthetic hypothesis and a synthetic method to access this complex core in one operation